Central Nervous System Histoplasmosis: A Retrospective Review of Clinical Characteristics, Treatments and Outcomes With Comparison to Disseminated Histoplasmosis Without Central Nervous System Involvement.

Abstract

Background: Central nervous system (CNS) histoplasmosis occurs in 5%-10% of patients with disseminated histoplasmosis, is sparsely described in the literature and is highly morbid.

Objectives: To evaluate clinical characteristics and outcomes of patients with CNS and non-CNS disseminated histoplasmosis.

Methods: In this retrospective case-control study, we matched 45 cases of CNS histoplasmosis with 45 controls with disseminated histoplasmosis without CNS involvement by hospital and date of encounter. Data were collected from three hospitals from January 2000 to December 2022 using histoplasmosis-related ICD-9/10 codes. Patients were classified as confirmed (Histoplasma growth on cerebrospinal fluid [CSF] or CNS culture), probable (positive CSF Histoplasma antigen or antibody), or possible (positive urine or serum Histoplasma antigen plus either CSF WBC ≥ 5 cells/μL or abnormalities on CNS imaging, with no other evident cause) CNS histoplasmosis.

Results: CNS (n = 45) and non-CNS disseminated histoplasmosis (n = 45) patients had similar demographic and clinical characteristics, although persons living with HIV (PLWH) were more prevalent in the CNS histoplasmosis group (93.3% and 80.0%, respectively, p = 0.019). CSF profiles (CSF WBC, glucose and total protein) and MRI brain imaging were normal in 28.2% and 21.9% of CNS histoplasmosis patients, respectively. CNS histoplasmosis patients were severely ill, with 34.1% requiring ICU care and Glasgow Outcome Scores of 1-4 in 51.1% of patients at discharge. In-hospital mortality was 6.7% for CNS vs. 13.3% for disseminated histoplasmosis (p = 0.215).

Conclusions: In this large CNS histoplasmosis cohort, we found an increased prevalence of PLWH in CNS vs. non-CNS disseminated histoplasmosis. Similar to prior CNS histoplasmosis cohorts, we report relatively high rates of normal CSF profiles (28.2%) and MRI brain imaging (21.9%). We also found significant morbidity in patients with CNS histoplasmosis, data which were not reported in prior cohorts.