DISSEMINATED ASPERGILLOSIS IN A PATIENT WITH NEUROSARCOIDOSIS ON INFLIXIMAB

Abstract

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Aspergillus fumigatus is a ubiquitous fungus associated with a variety of clinical syndromes. We report a case in which a patient with neurosarcoidosis but no underlying lung disease developed disseminated aspergillosis after starting infliximab therapy. CASE PRESENTATION: A 57 year old man with neurosarcoidosis on dexamethasone, infliximab, and methotrexate presented with two week history of shortness of breath and night sweats and one day history of right eye vision loss. Chest CT revealed new 3.6 cm cystic lung mass and three solid pulmonary nodules. MRI brain revealed innumerable ring-enhancing lesions in the right inferior frontal lobe measuring up to 3.7 cm. MRI spine revealed interval resolution of previously biopsied spinal granulomatous lesions. CSF studies and cultures were unremarkable. Serum Fungitell was > 500. Vitreous fluid culture from right eye and tissue culture from lung mass revealed Aspergillus fumigatus. The patient was treated with voriconazole. DISCUSSION: Aspergillus fumigatus is the most virulent species of Aspergillus. It is a ubiquitous saprotrophic fungus that can lead to a variety of clinical syndromes including allergic bronchopulmonary aspergillosis, aspergilloma, chronic cavitary pulmonary aspergillosis, invasive pulmonary aspergillosis, and disseminated aspergillosis. Severity of disease depends in part on size of inoculum, frequency of exposure, and host immune response. After inhalation, spores are removed by neutrophils and alveolar macrophages in normal hosts. Organisms that are not removed germinate into hyphae which are targeted by neutrophils. Given the significant role of neutrophils and macrophages in host defense against Aspergillus, immunodeficiency, particularly neutropenia and monocytopenia, represents the most significant risk factor for developing invasive aspergillosis. Other risk factors include underlying lung disease, critical illness, autoimmune diseases, and prolonged corticosteroid use. While lung disease is known to increase risk of invasive aspergillosis, our patient demonstrated neurosarcoidosis only, with no baseline pulmonary sarcoid involvement. Review of the literature reveals several case reports of fatal invasive aspergillosis with CNS involvement within months of starting infliximab therapy. TNFa inhibition has also been associated with poor fungal clearance and increased mortality in murine models of aspergillosis. These findings raise suspicion that TNFa inhibition may be an independent risk factor for the development of invasive aspergillosis. CONCLUSIONS: TNFa inhibition may be an independent risk factor for the development of invasive and disseminated aspergillosis, raising the question of whether screening or routine monitoring for fungal infections may be warranted for patients on anti-TNFa therapy. Reference #1: Tischler BY, Hohl TM. Menacing Mold: Recent Advances in Aspergillus Pathogenesis and Host Defense. J Mol Biol. 2019;431(21):4229–4246. doi:10.1016/j.jmb.2019.03.027. Reference #2: van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–674. doi:10.1038/nrmicro.2017.90. Reference #3: Bourne EL, Dimou J. Invasive central nervous system aspergillosis in a patient with Crohn's disease after treatment with infliximab and corticosteroids. J Clin Neurosci. 2016;30:163–164. doi:10.1016/j.jocn.2016.02.009. DISCLOSURES: No relevant relationships by Daniel Hershberger, source=Web Response No relevant relationships by Amber Johnson, source=Web Response