Hyalohyphomycosis (Fusariosis): Atypical Presentation in an Immunocompetent Individual Responding to Itraconazole.

Hyalohyphomycosis includes infections caused by various fungal species that produce hyaline, septate, branched hyphae. Fusarium is one such species which usually causes multiple papulo-nodules, ecthyma gangrenosum-like ulcers in immunocompromised individuals. Also, fusariosis is usually difficult to manage and responds favorably to amphotericin B, voriconazole, and posaconazole in disseminated cases. Here, we report an atypical case of cutaneous fusariosis in an immunocompetent individual who presented with multiple large cystic swellings, psoriasiform plaques, and palmoplantar keratoderma, and the patient responded completely to itraconazole.

PCR diagnostic platforms for non-Aspergillus mold infections: ready for routine implementation in the clinic?

INTRODUCTION: While Aspergillus spp. remain the predominant cause of invasive mold infections, non-Aspergillus molds, such as the Mucorales or Fusarium spp., account for an increasing proportion of cases. The diagnosis of non-Aspergillus invasive mold infections (NAIMI) is challenging because of the low sensitivity and delay of conventional microbiological tests. Therefore, there is a particular interest to develop molecular tools for their early detection in blood or other clinical samples. AREAS COVERED: This extensive review of the literature discusses the performance of Mucorales-specific PCR and other genus-specific or broad-range fungal PCR that can be used for the diagnosis of NAIMI in diverse clinical samples, with a focus on novel technologies. EXPERT OPINION: PCR currently represents the most promising approach, combining good sensitivity/specificity and ability to detect NAIMI in clinical samples before diagnosis by conventional cultures and histopathology. Several PCR assays have been designed for the detection of Mucorales in particular, but also Fusarium spp. or Scedosporium/Lomentospora spp. Some commercial Mucorales PCRs are now available. While efforts are still needed for standardized protocols and the development of more rapid and simpler techniques, PCR is on the way to becoming an essential test for the early diagnosis of mucormycosis and possibly other NAIMIs.

Onion Fusarium Basal Rot Disease Control by Arbuscular Mycorrhizal Fungi and Trichoderma harzianum.

Soilborne pathogens reduce 60% of the yield of onion crops. A common fungal pathogen causing wilt disease and severe losses is Fusarium basal rot (FBR). In this study, the combination of Arbuscular Mycorrhizal Fungi (AMF) with Trichoderma harzianum was investigated against FBR. Onion samples were collected from the Ankara-Polatli region. Among the isolates, isolate S6 was identified as F. oxysporum f. sp. cepae (FOC) using morphological and molecular methods and pathogenicity tests. Different combinations of AMF (Funneliformis mosseae pure strain and the commercial AMF) and T. harzianum were inoculated on susceptible onion cultivars (Seç, Gence, and Sampiyon). The effects of the treatments on FOC biocontrol were studied under growth chamber conditions. The results showed that Sampiyon was the most resistant, while Gence was the most susceptible to basal rot disease. Different colonization rates (8.91-24%), spore densities (16.4-50.4 spore/10 g soil), and the extent to which a plant needs mycorrhizal conditions to grow to its maximum potential (i.e., mycorrhizal dependencies-18.3-51.9%) were recorded by treatment. Both single and combined applications of AMF and Trichoderma applications suppressed FOC. Suppressive effects were more pronounced when the F. mosseae pure strain was used alone (when F. mosseae was used, disease severity decreased from 90 to 68%, p < 0.05). The F. mosseae pure strain also showed the best plant growth promotion and phosphorus content release. The results indicate an interesting potential use of F. mosseae and the combination of AMF with T. harzianum in the management of FOC in onions.

Multicenter Retrospective Study of Invasive Fusariosis in Intensive Care Units, France.

Invasive fusariosis can be life-threatening, especially in immunocompromised patients who require intensive care unit (ICU) admission. We conducted a multicenter retrospective study to describe clinical and biologic characteristics, patient outcomes, and factors associated with death and response to antifungal therapy. We identified 55 patients with invasive fusariosis from 16 ICUs in France during 2002----2020. The mortality rate was high (56%). Fusariosis-related pneumonia occurred in 76% of patients, often leading to acute respiratory failure. Factors associated with death included elevated sequential organ failure assessment score at ICU admission or history of allogeneic hematopoietic stem cell transplantation or hematologic malignancies. Neither voriconazole treatment nor disseminated fusariosis were strongly associated with response to therapy. Invasive fusariosis can lead to multiorgan failure and is associated with high mortality rates in ICUs. Clinicians should closely monitor ICU patients with a history of hematologic malignancies or stem cell transplantation because of higher risk for death.

Extensive primary cutaneous fusariosis in a patient with burns: A case report and review of the literature.

BACKGROUND: Fusarium species can cause a broad spectrum of human infections, ranging from superficial and locally invasive to disseminated, depending on the immune status of the host and portal of entry. Although several cases of cutaneous fusariosis in burn victims have been reported, molecular identification for pathogen recognition has been used only in a few cases. CASE DESCRIPTION: In this report, we describe an uncommon case of extensive primary cutaneous fusariosis caused by Fusarium keratoplasticum in a patient who sustained injuries during stubble burning. FINDINGS: A review of cases of cutaneous fusariosis in burn victims revealed that this uncommon infection could be lethal, and treatment strategies should focus on both surgical debridement and the initiation of systemic antifungal therapy. Furthermore, because skin defects can serve as a portal of entry for Fusarium species in burn victims, early and aggressive treatment is crucial to prevent serious consequences.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Invasive fusariosis.

SUMMARYInvasive fusariosis is a serious invasive fungal disease, affecting immunocompetent and, more frequently, immunocompromised patients. Localized disease is the typical clinical form in immunocompetent patients. Immunocompromised hosts at elevated risk of developing invasive fusariosis are patients with acute leukemia receiving chemotherapeutic regimens for remission induction, and those undergoing allogeneic hematopoietic cell transplant. In this setting, the infection is usually disseminated with positive blood cultures, multiple painful metastatic skin lesions, and lung involvement. Currently available antifungal agents have poor in vitro activity against Fusarium species, but a clear-cut correlation between in vitro activity and clinical effectiveness does not exist. The outcome of invasive fusariosis is largely dependent on the resolution of immunosuppression, especially neutrophil recovery in neutropenic patients.

Practical issues related to non-Aspergillus invasive mold infections.

Infection by non-Aspergillus molds has been increasingly reported. The management of such infections is challenging both for diagnosis and treatment, including the need of well-trained mycologists to properly identify rare fungi, difficulties in distinguishing between contamination, colonization and infection, the lack of randomized studies comparing different drugs or regimens, poor activity of available antifungal agents, lack of correlation between in vitro antifungal susceptibility tests and clinical outcome, and poor prognosis. Mucormycosis and fusariosis are the most frequent non-Aspergillus mold infections. Mucormycosis occurs more frequently in four major groups of patients: solid organ transplant recipients, patients with hematologic malignancies receiving chemotherapy or hematopoietic cell transplantation, diabetic patients, and immunocompetent individuals who suffer various types of skin and soft tissue trauma. Invasive fusariosis occurs almost exclusively in patients with hematologic malignancies. In this review we discuss practical issues related to the management of these and other non-Aspergillus mold infections.

Riesgo de mortalidad en infecciones invasoras por Fusarium spp en niños con enfermedades hemato-oncológicas: una revisión sistemática de la literatura

Introducción: Los estudios sobre la infección fúngica invasora (IFI) por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, son escasos, correspondiendo en general a series clínicas descriptas en forma retrospectiva, lo que dificulta conocer en profundidad sus características y evolución. Objetivo: Analizar la evolución fatal de la IFI causada por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, llevándose a cabo una revisión sistemática. Material y Métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de PubMed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de EbscoHOST), SCI-EXPANDED y Scielo (a través de la WOS) y Scopus (a través de Scopus-Elsevier) y libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1.341 artículos, de los cuales se descartaron 931 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 11 estudios. Todos los estudios eran de nivel 4 (serie de casos). Se detectó una notoria heterogeneidad (p < 0,008) entre los mismos. La mediana de la frecuencia de muerte observada implicó a un tercio de los afectados (Md 33 %; Q1:22,7-Q4:75). Conclusiones: La mortalidad por IFI por Fusarium spp fue alta en niños con patología hemato-oncológica, en especial en aquellos con neutropenia profunda y mala respuesta al tratamiento de su enfermedad de base

Background: Studies on invasive fungal infection (IFI) by Fusarium spp in pediatric patients with hemato-oncological pathology are scarce and limited and a few series of cases described retrospectively, which makes it difficult to fully understand their characteristics and outcome. With the aim of analyzing the fatal evolution of these patients, this systematic review was carried out. Methods: The literature search was performed up to March 23, 2023, in the main databases, as Medline (through PubMed), Embase (through Embase-Elsevier), The Cochrane Library (through Wiley), Cinahl (through EbscoHOST), SCI-EXPANDED and Scielo (through WOS) and Scopus (through Scopus-Elsevier) and free (through the Google engine) and reviewing the citations of the included articles. Results: 1341 articles were retrieved, of which 931 were discarded for various reasons. By analyzing its full texts, 11 studies were finally included. It was observed that heterogeneity among them was relevant (p < 0.008). Median frequency of death involved one third of those affected (Md 33%; Q1:22,7-Q4:75). Conclusions: Mortality due to IFI due to Fusarium spp was high in children with hemato-oncological pathology, especially in those with severe neutropenia and poor response to treatment of their underlying disease.

Fusariosis in patients with hematological malignancies: Two case reports.

Immunosuppressed patients with hematological malignancies are at risk for invasive fungal infections (IFI), including infections with Fusarium species (spp.), which are increasingly reported. Particularly at risk are patients with acute myeloid leukemia (AML) treated with high-dose cytarabine as remission-induction therapy. Whether cytarabine increases the risk of IFI in comparison to other chemotherapy remains not fully determined. Additionally, no clear correlation between the in vitro established minimal inhibitory concentrations (MICs) of antifungal agents and clinical outcome has been established for fusariosis. To increase awareness and knowledge of invasive fusariosis, we report two cases of Fusarium spp. infections in neutropenic patients following treatment with cytarabine for AML. Despite high MICs for azoles both patients were treated with an azole in combination with liposomal amphotericin B. The combination therapy was successful in one patient, however the other patient did not survive the disseminated Fusarium infection.

Utility of in-house and commercial PCR assay in diagnosis of Covid-19 associated mucormycoss in an emergency setting in a tertiary care center.

Introduction. Invasive mucormycosis (IM) is a potentially fatal infection caused by fungi of the order Mucorales. Histopathology, culture, and radiology are the mainstays of diagnosis, but they are not sufficiently sensitive, resulting in delayed diagnosis and intervention. Recent studies have shown that PCR-based techniques can be a promising way to diagnose IM.Hypothesis/Gap Statement. Early diagnosis of fungal infections using molecular diagnostic techniques can improve patient outcomes, especially in invasive mucormycosis.Aim. The aim of this study was to evaluate the utility of our in-house mould-specific real time PCR assay (qPCR) in comparison with the commercially available real time PCR (MucorGenius PCR), for the early diagnosis of mucormycosis in tissue samples from patients with suspicion of invasive mucormycosis (IM). This in-house assay can detect and distinguish three clinically relevant mould species, e.g. Aspergillus spp., Mucorales and Fusarium spp. in a single reaction with only one pair of primers, without the need for sequencing.Methodology. We enrolled 313 tissue samples from 193 patients with suspected IM in this prospective study. All cases were classified using EORTC/MSGERC guidelines. All samples were tested using traditional methods, in-house qPCR, and MucorGenius PCR.Results. Using direct microscopy as a gold standard, the overall sensitivity and specificity of in-house qPCR for detection of IM was 92.46% and 80% respectively, while that of the MucorGenius PCR was 66.67% and 90% respectively. However, co-infection of IM and IA adversely affected the performance of MucorGenius PCR in detection of IM.The in-house PCR detected Aspergillus spp. in 14 cases and Fusarium spp. in 4 cases which showed clinical and radiological features of fungal sinusitis. The in-house qPCR also performed better in detecting possible cases of IM. This aids early diagnosis and appropriate treatment to improve patient outcomes.Conclusion. Because the in-house PCR is not only sensitive and specific, but also entirely based on SYBR Green for detection of targets, it is less expensive than probe-based assays and can be used on a regular basis for the diagnosis of IM in resource-constrained settings. It can be used to distinguish between mucormycosis and fungal sinusitis caused by Aspergillus and Fusarium in high-risk patients, as well as to accurately detect Mucorales in fungal co-infection cases.

Treatment of Fusarium Infection of the Central Nervous System: A Review of Past Cases to Guide Therapy for the Ongoing 2023 Outbreak in the United States and Mexico.

INTRODUCTION: Fusariosis of the central nervous system (CNS) is extremely uncommon. Treatment and outcome data from previously published cases may provide some guidance in light of the ongoing fungal meningitis outbreak in 2023 involving Fusarium spp. in the United States and Mexico. METHODS: We reviewed the published literature describing cases of invasive fusariosis of the (CNS) that included data on patient demographic characteristics, treatment, and outcome. RESULTS: Twenty-six cases met inclusion criteria. The mean age was 36 years, 55% involved females, 60% had underlying hematologic malignancy, and another 16% were on immunosuppressants. The majority of infections were from Fusarium solani species complex. Overall 72% of patients died. The majority received monotherapy with amphotericin B, although some received voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole with or without adjuvant surgery. Among the survivors, 3 received amphotericin B monotherapy, 2 voriconazole monotherapy, 1 combination therapy of both, and one surgery only. CONCLUSION: The overall mortality rate in published cases of fusariosis of the CNS was high, although-unlike during the current outbreak-the preponderance of patients were severely immunocompromised. While historically the majority were treated with amphotericin B monotherapy, some recent patients were treated with voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole. Current guidelines recommend monotherapy with voriconazole or lipid formulations of amphotericin B or combination of both for the treatment of invasive fusariosis, which is in line with the findings from our literature review and should be considered during the ongoing 2023 outbreak.

Cell wall-related genes and lignin accumulation contribute to the root resistance in different maize (Zea mays L.) genotypes to Fusarium verticillioides (Sacc.) Nirenberg infection.

Introduction: The fungal pathogen Fusarium verticillioides (Sacc.) Nirenberg (Fv) causes considerable agricultural and economic losses and is harmful to animal and human health. Fv can infect maize throughout its long agricultural cycle, and root infection drastically affects maize growth and yield. Methods: The root cell wall is the first physical and defensive barrier against soilborne pathogens such as Fv. This study compares two contrasting genotypes of maize (Zea mays L.) roots that are resistant (RES) or susceptible (SUS) to Fv infection by using transcriptomics, fluorescence, scanning electron microscopy analyses, and ddPCR. Results: Seeds were infected with a highly virulent local Fv isolate. Although Fv infected both the RES and SUS genotypes, infection occurred faster in SUS, notably showing a difference of three to four days. In addition, root infections in RES were less severe in comparison to SUS infections. Comparative transcriptomics (rate +Fv/control) were performed seven days after inoculation (DAI). The analysis of differentially expressed genes (DEGs) in each rate revealed 733 and 559 unique transcripts that were significantly (P ≤0.05) up and downregulated in RES (+Fv/C) and SUS (+Fv/C), respectively. KEGG pathway enrichment analysis identified coumarin and furanocoumarin biosynthesis, phenylpropanoid biosynthesis, and plant-pathogen interaction pathways as being highly enriched with specific genes involved in cell wall modifications in the RES genotype, whereas the SUS genotype mainly displayed a repressed plant-pathogen interaction pathway and did not show any enriched cell wall genes. In particular, cell wall-related gene expression showed a higher level in RES than in SUS under Fv infection. Analysis of DEG abundance made it possible to identify transcripts involved in response to abiotic and biotic stresses, biosynthetic and catabolic processes, pectin biosynthesis, phenylpropanoid metabolism, and cell wall biosynthesis and organization. Root histological analysis in RES showed an increase in lignified cells in the sclerenchymatous hypodermis zone during Fv infection. Discussion: These differences in the cell wall and lignification could be related to an enhanced degradation of the root hairs and the epidermis cell wall in SUS, as was visualized by SEM. These findings reveal that components of the root cell wall are important against Fv infection and possibly other soilborne phytopathogens.

An unusual presentation of invasive Fusarium aortitis in a patient who is immunocompromised: A case report.

Fusarium (F.) species are ubiquitous filamentous fungi that may cause various opportunistic infections, especially in patients who are immunocompromised. A rare manifestation of disseminated fusariosis affects the aortic valve and results in invasive aortitis, which poses a significant challenge for clinicians in diagnosis and treatment. Here, we report a case of a patient, aged 54 years, who is immunocompromised, presenting initially with Fusarium keratitis and chorioretinitis in both eyes and a new endovascular aortic mass. Positron emission tomography/computed tomography was performed, suggesting aortitis. Transoesophageal echocardiography and electrocardiogram-guided computed tomography-angiography confirmed a large intraluminal mass in the ascending aorta. The aortic mass and a part of the ascending aorta were resected surgically, and a filamentous fungus with the microscopic features of the genus Fusarium was isolated and later identified molecularly as F. petroliphilum. The course of the treatment was complicated by perioperative cerebral embolization and mesenteric ischemia. These complications could be attributed to a preoperatively existing occlusion of the superior and inferior mesenteric artery and a subtotal stenosis of the celiac trunk. This case report describes a rare manifestation of disseminated fusariosis, frequently characterized by protracted clinical courses with poor prognosis. Fusariosis may manifest at different sites at different times or persist as a long-lasting disease with reactivation. This case highlights the importance of the interdisciplinary approach for effectively treating invasive mycoses.

Evolution of antifungals for invasive mold infections in immunocompromised hosts, then and now.

INTRODUCTION: The current armamentarium of antifungal agents for invasive mold infections (IMI) has dramatically improved over the last 50 years. Existing therapies are, however, associated with toxicities, drug interactions, and, in some cases, therapeutic failures. Novel antifungals are needed to address the increasing prevalence of IMI and the growing threat of antifungal resistance. AREAS COVERED: We review the history and development of the most commonly used antifungals. We discuss the current consensus guidelines and supporting data for treatment of invasive mold infection (IMI), the role of susceptibility testing, and the niche that novel antifungals could fill. We review the current data for aspergillosis, mucormycosis, and hyalohyphomycosis. EXPERT OPINION: Robust clinical trial data demonstrating the relative effectiveness of our current antifungal agents for treating IMI outside of A. fumigatus remains limited. Clinical trials are urgently needed to delineate the relationship between MICs and clinical outcomes for existing agents and to better evaluate the in vitro and in vivo aspects of antifungal synergy. Continued international multicenter collaboration and standardized clinical endpoints for trials evaluating both existing and new agents are necessary to advance the field.

Fusarium solani species complex infection treated with posaconazole in a liver transplantation patient; a case report.

Although Fusarium spp. rarely cause infections in healthy people, they can cause fusariosis, particularly in neutropenic hematological malignancies, bone marrow transplant patients, and immunocompromised patients, such as those with acquired immune deficiency syndrome (AIDS), and rarely in solid organ transplant recipients. Here, we present a case of a liver transplant recipient with F. solani species complex (FSSC) infection treated with posaconazole. A 61-year-old man presented with multiple itchy, painful, palpable, irregular, subcutaneous nodules on the right leg and total dystrophic onychomycosis in the right toenails. Incisional skin biopsies of the lesions were performed, and the samples were sent to the pathology and mycology laboratories for analysis. The clinical isolate was identified as FSSC using phenotypic, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and genotypic methods. Liposomal amphotericin B could not be administered owing to the development of side effects; hence, the patient was treated with posaconazole for 4 months. While some nodular lesions disappeared completely under this treatment, the others showed dimensional regression. This is the first case of FSSC infection with skin and nail involvement in a non-neutropenic, liver transplant patient in Turkey. Fusariosis may develop with rare species, such as FSSC, as first reported in this case of a liver transplant patient. Regardless of the species, amphotericin B is the first choice for treating fusariosis; however, posaconazole is an effective and safe alternative to amphotericin B.

Superficial fungal infections in the south of France-is fusariosis the next emergent onychopathy?

In France, onychomycoses represent about 30% of superficial mycoses seen by dermatologists. In recent years, an increased number of mycoses have been observed due to non-dermatophytic moulds. The purpose of this study was to evaluate the epidemiological profile of identified superficial fungal infections in the Laboratory of Parasitology-Mycology of the University Hospital of Nice over a 2-year period. A retrospective study was performed from the nail, skin, and scalp samples of patients analyzed from January 2018 to December 2019. In this study, 3074 samples (54.2% nails, 39.7% skin, and 6.1% scalp) were analyzed representing 1922 patients. Among them, 809 (42.1%) patients were sampled by dermatologists and 1113 (57.9%) were sampled by our experts in the clinical unit of the University Hospital of Nice. In total, 1159 (37.7%) samples had a positive culture (1195 strains identified) including 712 (59.6%) dermatophytes, 345 (28.9%) yeasts, and 138 (11.5%) other filamentous moulds. Trichophyton rubrum was the main dermatophyte (563; 47.1%) followed by T. interdigitale (84; 7.0%), and T. soudanense (25; 2.1%). Yeasts were mostly represented by Candida albicans (155; 13.0%). Among the other moulds, Fusarium sp. was the most isolated (61; 5.1%). Dermatophytes stay predominant in superficial fungal infections where the anthropophilic species T. rubrum was found in almost half of the positive cultures. Interestingly, moulds represented an important part of infections in our population. This study highlights the increasing share of Fusarium sp. superficial fungal infection in our patients' population, perhaps requiring a major therapeutic adaptation in the years to come.

We assessed the epidemiological profile of superficial fungal infections in the Laboratory of Parasitology­Mycology of the Hospital of Nice, over a 2-year period. Among our samples, dermatophytes remain predominant, mainly the species Trichophyton rubrum and we had a large proportion of Fusarium.

Clinical Features and Outcomes of Invasive Fusariosis: A Case Series in a Single Center with Literature Review.

Fusarium species, which are commonly found in soil, water, and organic substrates, can cause serious infections especially in immunocompromised patients. Fusarium infection is notoriously difficult to treat, because of their inherently high minimum inhibitory concentrations (MICs) to most antifungal agents. There have been limited data on invasive fusariosis in Korea. We identified 57 patients with culture-proven fusariosis at Samsung Medical Center, Seoul, Korea, from September 2003 through January 2017. Invasive fusariosis was defined as any case with at least one positive blood culture or with concurrent involvement of 2 or more non-contiguous sites. Superficial infections such as keratitis and onychomycosis were excluded. We reported 14 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, of which 6 cases were fusarium fungemia. Hematologic malignancies (7/14, 50%), solid organ transplantation (2/14, 14.2%), or immunosuppressive therapy (2/14, 14.2%), were the predominant underlying conditions. The overall mortality rate was 37%, however, that of disseminated fusariosis was up to 83%. Antifungal treatment with voriconazole or liposomal amphotericin B was commonly administered. In this report, we described the clinical characteristics and treatment outcomes of invasive fusariosis in Korea. Given the high mortality in disseminated cases, invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients.

Primary Invasive Cutaneous Fusariosis in Patients with STAT3 Hyper-IgE Syndrome.

Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host's innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory-occasionally granulomatous-infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients.