To review and analyze case reports of dermatophytosis caused by species of the T. mentagrophytes complex during the 2020–2026 period to understand the current clinical and mycological characteristics of these fungal infections. Dermatophytosis caused by the T. mentagrophytes complex is characterized by a variable response to antifungal agents, atypical lesions, novel transmission routes, and difficulties in differentiating species within the complex, therefore, a molecular approach is required to accurate species identification. This situation forces dermatologists to adopt new strategies to achieve a specific diagnosis that leads to effective antifungal treatment and the establishment of appropriate prevention or control measures. There has been an increase in reported cases of dermatophytosis caused by the T. mentagrophytes complex, which could reveal an emerging public health problem that requires attention due to the variable response to antifungal agents, the extensive and severe lesions, and sexual transmission. Dermatologists should adopt new strategies focused on the use of phenotypic and molecular tests, combined with a thorough medical history and patient anamnesis, to achieve a specific diagnosis and effective antifungal treatment, as well as the establishment of prevention and control measures.
Fungal infections represent a significant global health challenge, encompassing highly prevalent superficial mycoses and increasingly frequent invasive fungal diseases associated with substantial morbidity and mortality. Conventional antifungal therapies are often limited by poor skin and nail penetration, suboptimal bioavailability, systemic toxicity, and the emergence of antifungal resistance, resulting in prolonged treatment regimens and high recurrence rates. Ethosomal drug delivery systems, composed of phospholipids and high ethanol content, have emerged as advanced vesicular carriers capable of overcoming these limitations through enhanced membrane fluidization, vesicle deformability, and efficient transdermal and mucosal penetration. This review critically examines the concept, composition, and penetration mechanisms of ethosomes with a focused emphasis on antifungal drug delivery. Reported ethosomal formulations of azoles, polyenes, allylamines, echinocandins, and herbal antifungals are systematically analyzed with respect to physicochemical properties, skin and nail permeation, antifungal efficacy, and safety outcomes. Quantitative evidence from in vitro, ex vivo, in vivo, and emerging clinical studies demonstrates superior drug deposition, faster fungal clearance, reduced systemic toxicity, and improved patient compliance compared to conventional and other vesicular systems. Overall, ethosomal drug delivery represents a promising and clinically relevant approach for improving the management of both superficial and systemic fungal infections. However, further large-scale clinical studies and regulatory standardization are required for successful clinical translation. Clinically, ethosomes should therefore be interpreted as an indication-specific enabling platform rather than an immediate replacement for effective standard antifungal therapy, because routine superficial infections are often controlled with existing topical or oral agents and the therapeutic landscape is evolving through recently approved or late-stage antifungal compounds and adjunctive immunotherapeutic approaches.
This study aimed to elucidate the cellular and molecular mechanisms underlying the interaction between macrophages and Trichophyton rubrum in the presence of a curcumin analog. RNA-seq and transcriptomic analyses of mRNA and microRNAs using the co-culture model revealed that the presence of T. rubrum strongly modulates gene expression in THP-1 cells, with dozens of genes being upregulated or downregulated (involving signaling pathways, cell communication, inflammation, and immune response). Additionally, the co-culture model can be used to evaluate the response of macrophages infected with T. rubrum in the presence of novel antifungal molecules. Trichophyton rubrum is the primary causative agent of superficial mycoses worldwide; however, it has been increasingly associated with invasive infections, particularly in immunocompromised and diabetic patients. Curcumin analogs exhibit promising antifungal and anti-inflammatory activity. The invasive infectious process involves initial contact between the pathogen and the host, pathogen adherence, tissue invasion, and activation of the immune response. Nevertheless, this process remains incompletely understood, especially in the presence of new antifungal compounds. A co-culture model was established using previously germinated and heat-inactivated T. rubrum conidia in contact with THP-1 exposed to curcumin analog for 24 h. This study demonstrated that the synthetic curcuminoid 2102 exhibits potent antifungal activity against T. rubrum, with low minimum inhibitory concentration and reduced cytotoxicity in THP-1-derived macrophages. In co-culture, curcuminoid was able to modulate the inflammatory response, significantly decreasing the release of IL-1β, IL-12, and TNF-α, while promoting a dose-dependent increase in the production of reactive oxygen species, suggesting a dual role in both controlling fungal growth and enhancing cellular defense mechanisms. These findings highlight the potential of the curcuminoid 2102 as a promising candidate for the development of novel antifungal therapies, especially in the context of drug-resistant dermatophyte infections.
Despite the availability of potent antifungal compounds, invasive fungal diseases (IFD) are still a major cause for morbidity and mortality in immunocompromised pediatric and adult patients, and risk and outcome of IFDs are determined by the degree of the suppression of the specific arms of the immune system. This prompted us to review the current knowledge of immunotherapeutic antifungal approaches. We critically review important in vitro and animal data as well as clinical studies of immunotherapy for IFD, in particular granulocyte transfusion, the adoptive transfer of primary and genetically modified Natural Killer cells and fungal-specific T cells, and the use of colony-stimulating factors and cytokines. Although promising data of in vitro and animal models have been reported for many strategies, no clear benefit has been demonstrated in the clinical setting to date.
The review summarizes the existing literature on epidemiology, pathogenesis, the clinical spectrum, and manifestations, as well as diagnostic testing and treatment of coccidioidomycosis, and discusses the role of cutaneous manifestations in facilitating early diagnosis. The recent literature emphasizes a variety of clinical manifestations, confirms the added value of combining histopathology/serology, culture, and molecular tests to increase diagnosis accuracy, but also reinforces triazoles as the first-line therapy. Increasing evidence also highlights the host Th1 and Th17 immune response, as well as genomic virulence factors, as key drivers of disease heterogeneity. Early identification of cutaneous signs is crucial for effective treatment, limiting the spread of the disease, and improving outcomes. Severe or refractory disease often requires amphotericin B. Future research should focus on refining rapid diagnostics, risk prediction, and optimized antifungal regimens in both endemic and nonendemic settings. These priorities may guide prospective studies and standardized management pathways to enhance outcomes in diverse populations worldwide.
