Iatrogenic Exserohilum Infection of the Central Nervous System

Mycological Identification and Histopathological Findings

W Robert Bell; Justin B Dalton; Chad M McCall; Sarah Karram; David T Pearce; Warda Memon; Richard Lee; Karen C Carroll; Jennifer L Lyons; Elakkat D Gireesh; Julie B Trivedi; Deanna Cettomai; Bryan R Smith; Tiffany Chang; Laura Tochen; John N Ratchford; Daniel M Harrison; Lyle W Ostrow; Robert D Stevens; Li Chen; Sean X Zhang

Disclosures

Mod Pathol. 2013;26(2):166-170. 

In This Article

Abstract and Introduction

Abstract

An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an index case of Exserohilum meningitis and vasculitis in an immunocompetent patient, who received a cervical spine epidural steroid injection for chronic neck pain 1 week before the onset of fulminant meningitis with subsequent multiple brain and spinal cord infarcts. The fungus was recovered from two separate cerebrospinal fluid specimens collected before initiation of antifungal therapy and at autopsy on standard bacterial and fungal culture media. The mold was identified phenotypically as Exserohilum species. DNA sequencing targeting the internal transcribed spacer region and D1/D2 region of 28S ribosomal DNA enabled further speciation as E. rostratum. Gross examination at autopsy revealed moderate brain edema with bilateral uncal herniation and a ventriculostomy tract to the third ventricle. The brainstem, cerebellum, and right orbitofrontal cortex were soft and friable, along with hemorrhages in the cerebellar vermis and thalamus. Microscopic examination demonstrated numerous fungi with septate hyphae invading blood vessel walls and inducing acute necrotizing inflammation. The leptomeninges were diffusely infiltrated by mixed inflammatory cells along with scattered foci of fungal elements. This is the first report of iatrogenic E. rostratum meningitis in humans. This report describes the microbiological procedures and histopathological features for the identification of E. rostratum (a pigmented vascularly invasive fungi), the cause of a current nationwide outbreak of fatal fungal meningitis.

Introduction

Dematiaceous fungi are ubiquitous in the environment. They are characterized by the presence of melanin in their cell walls and are not a common cause of human disease. Nonetheless, a spectrum of clinical presentations associated with dematiaceous fungi has been reported including superficial and deep local infections, allergic disease, pneumonia, brain abscess and disseminated disease.[1] Infection is thought to result from either trauma to the skin, inhalation, or hematogenous spread from a remote sub-acute infection.[1,2] In the central nervous system, the formation of a brain abscess has been the most common finding, frequently occurring in immunocompetent individuals.[2] In 2002, iatrogenic meningitis caused by a dematiaceous fungus Exophiala was observed as a complication of contaminated epidural glucocorticoid injections.[3,4] Presently, the Exserohilum has been identified as the most common and important organism in an ongoing multistate outbreak after an initial alert was generated due to an Aspergillus infection.[5,6] Given the rarity of these organisms as causative agents of meningitis, accurate diagnosis rests largely on mycological and pathologic description. Here, we present the mycological and histopathological findings in one of the index cases of Exserohilum-associated meningitis and vasculitis in the current nationwide outbreak, the clinical and neuroradiological findings of which were recently reported.

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