Update on disseminated cryptococcosis in non-HIV infected children.

Background: Disseminated cryptococcosis is a rare disease in children, especially in children with normal immunity. The understanding of this disease needs to be improved. This study aims to update the global situation of disseminated cryptococcosis in non-HIV infected children for the first time.

Methods: The clinical data of a child with disseminated cryptococcosis was retrospectively analyzed, and disseminated cryptococcosis clinical features of published studies were summarized. Electronic databases were searched in February 2025. Clinical studies that meet the criteria were included in the present study.

Results: Totally 116 cases were analyzed in this study, including 1 case in our center and 115 cases from 45 studies. The cohort included 82 males (70.7%) and 34 females (29.3%), with ages ranging from 10 months to 18 years. The main clinical manifestations were fever (79.3%), respiratory symptoms (41.4%), and neurological symptoms (39.7%), followed by hepatosplenomegaly (35.3%), rash (27.6%), lymphadenopathy (18.1%), and gastrointestinal symptoms (16.4%). The most commonly affected organs were the lungs (77.6%), central nervous system (53.4%), and lymph nodes (51.7%). Immunodeficiency was present in 12.9% of children (3.4% domestic cases vs. 9.5% foreign cases). Elevated eosinophils were observed in 43 patients (37.1%), and elevated IgE levels in 35 patients (30.2%). The most common pathogen-positive specimens were cerebrospinal fluid (54 cases, 46.6%), blood cultures (49 cases, 42.2%), lymph node biopsies (26 cases, 22.4%), bone marrow (18 cases, 15.5%), and skin samples (8 cases, 6.9%). Combination therapy was administered to 89 patients (76.7%), while 21 patients (18.1%) received monotherapy. Clinical improvement occurred in 94 patients (81.0%), with 15 fatal cases.

Conclusions: Disseminated cryptococcosis in children often presents with fever, respiratory and neurological symptoms, with the lungs, central nervous system, and lymph nodes being the most frequently involved organs. Most cases do not have immunodeficiency or underlying diseases, and blood tests often reveal eosinophilia and elevated IgE levels. The positive detection rates of pathogens are relatively high in blood cultures, cerebrospinal fluid, bone marrow cultures, and lymph node biopsies. The majority of patients achieved favorable therapeutic outcomes with combination therapy.