title: Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings.
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.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-7093, USA.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Bell
authors.forename: Justin B
authors.initials: JB
authors.lastname: Dalton
authors.forename: Chad M
authors.initials: CM
authors.lastname: McCall
authors.forename: Sarah
authors.initials: S
authors.lastname: Karram
authors.forename: David T
authors.initials: DT
authors.lastname: Pearce
authors.forename: Warda
authors.initials: W
authors.lastname: Memon
authors.forename: Richard
authors.initials: R
authors.lastname: Lee
authors.forename: Karen C
authors.initials: KC
authors.lastname: Carroll
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Lyons
authors.forename: Elakkat D
authors.initials: ED
authors.lastname: Gireesh
authors.forename: Julie B
authors.initials: JB
authors.lastname: Trivedi
authors.forename: Deanna
authors.initials: D
authors.lastname: Cettomai
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Smith
authors.forename: Tiffany
authors.initials: T
authors.lastname: Chang
authors.forename: Laura
authors.initials: L
authors.lastname: Tochen
authors.forename: John N
authors.initials: JN
authors.lastname: Ratchford
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Harrison
authors.forename: Lyle W
authors.initials: LW
authors.lastname: Ostrow
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Sean X
authors.initials: SX
authors.lastname: Zhang
mesh_terms: D001203:Ascomycota / Q000302:isolation & purification*; D001921:Brain / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007268:Injections, Epidural / Q000009:adverse effects*; D016921:Meningitis, Fungal / Q000209:etiology / Q000382:microbiology / Q000473:pathology*; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology*