Exploring the Depths of Cryptic Aspergillosis: Species Variability, Clinical Spectrum, Diagnostic Quandaries and Therapeutic Options

Cryptic aspergillosis, characterised by infections caused by non classical Aspergillus species, presents unique challenges in clinical management due to species variability, diverse clinical manifestations, diagnostic complexities, and limited treatment options. This comprehensive review explores the emerging understanding of cryptic aspergillosis, highlighting the spectrum of clinical presentations across different species, diagnostic dilemmas in accurate species identification, and evolving treatment paradigms. Cryptic species, including A. lentulus, A. udagawae, A. calidoustus, and others, exhibit intrinsic resistance to commonly utilised antifungal agents, complicating therapeutic approaches. The diagnostic landscape is further complicated by phenotypic and genotypic similarities with classical Aspergillus species, necessitating advanced molecular techniques for precise identification. Treatment alternatives are limited, with azoles, echinocandins, and polyenes demonstrating variable efficacy against different cryptic species. Emerging antifungal agents, like fosmanogepix, ibrexafungerp, and rezafungin, hold promise in addressing resistance challenges. This review underscores the need for a multidisciplinary approach integrating clinical, microbiological, and molecular expertise to optimise the management of cryptic aspergillosis and improve patient outcomes.