Clinical, radiological and laboratory characteristics of central nervous system histoplasmosis: A systematic review of a severe disease

Abstract

Background:The knowledge of central nervous system (CNS) histoplasmosis is limited to case reports and series.Objectives: Our objective was to synthesise clinical, radiological and laboratory characteristics of CNS histoplasmosis to improve our understanding of this rare disease. Methods:We performed a systematic review using Pubmed/MEDLINE, Embase and LILACS databases accessed on March 2023 without publication date restrictions.Inclusion criteria comprised: (1) histopathological, microbiological, antigen or serological evidence of histoplasmosis; (2) CNS involvement based on cerebrospinal fluid pleocytosis or neuroimaging abnormalities. We classified the certainty of the diagnosis in proven (CNS microbiological and histopathological confirmation), probable (CNS serological and antigen confirmation) or possible (non-CNS evidence of histoplasmosis). Metaproportion was used to provide a summary measure with 95% confidence intervals for the clinical, radiological and laboratory characteristics. Chi-squared test was used to compare mortality between pairs of antifungal drugs. Results:We included 108 studies with 298 patients. The median age was 31 years, predominantly male, and only 23% were immunocompromised (134/276, 95%CI: 3-71), mainly due to HIV infection. The most common CNS symptom was headache (130/236, 55%, 95%CI: 49-61), with a duration predominantly of weeks or months.Radiological presentation included histoplasmoma (79/185, 34%, 95%CI: 14-61), meningitis (29/185, 14%, 95%CI: 7-25), hydrocephalus (41/185, 37%, 95%CI: 7-83) and vasculitis (18/185, 6%, 95%CI: 1-22). There were 124 proven cases, 112 probable cases and 40 possible cases. The majority of patients presented positive results in CNS pathology (90%), serology (CSF: 72%; serum: 70%) or CSF antigen (74%). Mortality was high (28%, 56/198), but lower in patients who used liposomal amphotericin B and itraconazole. Relapse occurred in 13% (23/179), particularly in HIV patients, but less frequently in patients who used itraconazole. Conclusion:Central nervous system histoplasmosis usually presents subacute-tochronic symptoms in young adults. Neuroimaging patterns included not only focal lesions but also hydrocephalus, meningitis and vasculitis. Positive results were

Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta‐analysis

“…Some patients were empirically treated for tuberculous meningitis 11,17 because of overlapping clinical, CSF, and radiological findings. When compared with other CNS infections by endemic mycoses, such as paracoccidioidomycosis and histoplasmosis, sporotrichosis had the highest mortality rate 40,41 . Possibly, this occurs due to a high proportion of immunosuppressed patients.…”

Endemic mycoses – are we making progress in management?

“…The most compelling candidate is isavuconazole which has low in vitro minimum inhibitory concentrations (MICs) in Histoplasma isolates from patients who failed treatment with fluconazole as opposed to voriconazole which had high MICsboth have good CNS penetration [21][22][23][24][25][26]. In a 2023 systematic review of CNS histoplasmosis, mortality was 12% (9/73) in those treated with itraconazole and 20% (3/15) in those treated with voriconazole [27]. Although the P value for the comparison was 0.43, it's difficult to say whether or not there is a true difference in efficacy based on this data, particularly given the sample size and lack of correction for potential confounders.…”