Between Skin and Brain: A Systematic Review of 712 Cases 1976–2025 Reveals a Highly Diverse Disease Spectrum in Chaetothyriales

BACKGROUND: Black yeast-like species of the order Chaetothyriales cause superficial to life-threatening systemic infections. Comprehensive global epidemiology data remain limited. OBJECTIVES: This study aimed to analyze the global epidemiology, spectrum of pathogens, clinical manifestations and outcomes of Chaetothyriales infections. METHODS: We systematically reviewed 712 cases reported between 1976 and 2025. RESULTS: The analysis revealed a steady increase in diagnosed cases, with Cladophialophora bantiana (21%), Exophiala dermatitidis (19%), and E. jeanselmei (15%) being the predominant causative agents; notably, the proportion of E. jeanselmei declined from 18%-28% in 1976-2015 to 7% in 2016-2025. Published cases were more frequent in tropical/subtropical regions; however, cases were reported from Africa. Although 42% of infections occurred in immunocompetent individuals, transplant recipients, diabetics, and those with CARD9 deficiency showed higher risk. Deep infections exhibited substantially greater mortality than cutaneous forms (47% vs. 7%; p < 0.001); particularly, central nervous system infections (58%) and disseminated disease (53%) were involved. CONCLUSIONS: This study highlights a seemingly growing burden of Chaetothyriales infections, possibly partly due to better recognition, emphasizing the need for improved surveillance, diagnostics, and targeted prevention in high-risk populations.