CNS Histoplasmosis Most Common in Young Immunocompromised Men

Mortality in CNS histoplasmosis is high, and treatment with liposomal amphotericin B followed by itraconazole may decrease mortality.

Central nervous system (CNS) histoplasmosis typically presents with subacute to chronic symptoms, according to a review published in Mycoses.

Researchers conducted a review to synthesize a more complete understanding about features that may guide future clinical guidelines about CNS histoplasmosis. The review comprised 108 manuscripts published between 1962 and 2022 that comprised 298 patients.

Participants were a median age of 31 years, 67% were men, 94% were from the Americas, 63% had HIV, 16% received a solid organ transplant, and 100% had a CD4 count below 150 cells/mm3.

The participants presented with headache (55%), altered mental state (42%), focal weakness (33%), neck stiffness (29%), visual complaints (16%), seizures (13%), and ataxia (11%). These CNS symptoms most commonly had a duration of more than 26 weeks (23%), 5 to 26 weeks (32%), or 2 to 4 weeks (22%).

Central nervous system histoplasmosis is an endemic disease reported mainly in the Americas that causes subacute-to-chronic neurological manifestations, predominantly in young males.

In addition, the participants presented with extra-neurological symptoms involving the lungs (56%), bone marrow (37%), lymph nodes (23%), adrenals (20%), skin (11%), liver (10%), spleen (10%), and gastrointestinal tract (9%).

During radiological assessment, 18% had no abnormalities. The remaining participants were found to have hydrocephalus (37%), histoplasmoma (34%), meningitis (14%), and vasculitis (6%). Among those with histoplasmoma, most presented with multiple lesions (67%) and the most common lesion locations were supratentorial (61%), infratentorial (42%), brainstem (28%), and spinal cord (22%).

According to laboratory findings, 124 cases were proven, 112 were probable, and 40 were possible. An additional 22 cases did not have sufficient data to classify.

Most (88%) cerebrospinal fluid (CSF) findings were abnormal. The median CSF leukocyte count was 65 (IQR, 45-93) cells/mL, mean protein concentration was 151 (IQR, 126-212) mg/dL, and mean glucose concentration was 34 (IQR, 28-40) mg/dL.

The CSF serology by enzyme immunoassay returned a higher positive frequency (77%) than the serology by immunodiffusion (54%). The median titers of Histoplasma complement-fixation antibodies were 1:8 in CSF and 1:64 in serum, and in yeast form were 1:8 and 1:32, respectively.

The participants were treated with the antifungals amphotericin B (84%), liposomal amphotericin (40%), itraconazole (24%), deoxycholate amphotericin (19%), lipid complex amphotericin (13%), fluconazole (11%), and voriconazole (8%). A total of 11% of participants underwent surgical intervention.

The relapse rate was 13% and the overall mortality rate was 28%.

Among the participants who relapsed, more had HIV (52% vs 29%; P =.02) and fewer received itraconazole (33% vs 61%; P =.03) compared with those who did not relapse, respectively.

Mortality was higher among amphotericin B lipid complex recipients compared with liposomal amphotericin B recipients (39% vs 15%; P =.01) and among fluconazole recipients compared with itraconazole recipients (44% vs 12%; P <.001), respectively.

The review authors conclude, “Central nervous system histoplasmosis is an endemic disease reported mainly in the Americas that causes subacute-to-chronic neurological manifestations, predominantly in young males.”


de Oliveira VF, Kruschewsky WLL, Sekiguchi WK, et al. Clinical, radiological and laboratory characteristics of central nervous system histoplasmosis: a systematic review of a severe disease. Mycoses. Published online May 3, 2023. doi:10.1111/myc.13600