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Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021–2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

Background Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by dematiaceous fungi that mainly affects rural workers in tropical and subtropical regions. The disease poses a treatment challenge due to its refractory nature and high relapse rate. To date, few cases have been reported in Peru. Methods We retrospectively reviewed epidemiological, clinical, microbiological, and treatment data from CBM cases diagnosed between 2011 and 2024 at the Clinical Mycology Unit of the Instituto de Medicina Tropical Alexander von Humboldt (IMTAvH) in Lima, Peru. Diagnosis was confirmed by the identification of muriform cells either on direct microscopic examination or histopathology. Results Of the 15 identified cases, 13 had sufficient data for inclusion. In summary, 84% of the patients were men, 77% acquired the disease in the Peruvian Amazon jungle (predominantly in Ucayali and San Martin), the median age was 65.3 years (range: 33–85), and the average disease duration was 10.7 years (range: 1–25 years). The lower extremities were most frequently affected (53%), followed by the upper extremities (38%). Plaque-like and verrucous lesions were the most common (38% each), whereas tumoral and cicatricial forms were less frequent (15% each). The aetiological agent was identified by morphology in nine patients. Fonsecaea sp. was the most frequently identified pathogen (46%), followed by Cladophialophora sp. (15%) and Phialophora sp. (7%). Nine patients (69%) received oral itraconazole (200–400 mg/day) combined with cryosurgery; two (15%) received itraconazole alone; and two (15%) received itraconazole combined with terbinafine (500 mg/day). Treatment duration ranged from 5 to 136 months, with six patients (46%) achieving a cure. Conclusions CBM in Peru is likely underdiagnosed and underestimated due to low disease recognition, limited diagnostics in remote areas, and lack of mandatory reporting.

Chromoblastomycosis (CBM) and mycetoma, as implantation mycoses, have been listed as neglected tropical diseases (NTDs) by the World Health Organization. The concurrent occurrence of these two NTDs in a single patient is extremely rare. A 69-year-old female patient presented with papules on the dorsum of her left hand for over 5 months and nodules on the left lower limb accompanied by ulceration and pain for 20 days. Histopathological examination of the papule on the dorsum of the left hand revealed muriform cells and fungal culture of the tissue identified Fonsecaea monophora . Microscopic examination of the purulent secretion from the ulcer on the left lower calf revealed the presence of grains, and the tissue culture result was Scedosporium apiosperma complex, with metagenomic next-generation sequencing further identifying S. dehoogii as the predominant pathogen. The clinical diagnosis was CBM caused by F. monophora combined with eumycetoma due to S. dehoogii. The patient was treated with voriconazole at a dosage of 200 mg twice daily for 4 weeks, after which the papules on the dorsum of the left hand and the ulcer on the left lower calf showed gradual improvement. This case represents the first reported instance of concurrent CBM caused by F. monophora and eumycetoma due to S. dehoogii , providing a novel perspective on the clinical manifestations and early identification of neglected implantation mycoses.

Chromoblastomycosis (CBM) is a subcutaneous fungal infection caused by one of several dematiaceae molds with melanotic pigmentation in the cell walls. CBM is characterized by various clinical and dermatological features, leading to common misdiagnosis as several other infectious and noninfectious diseases. Histopathologically, in addition to the pathognomonic muriform cells or \"copper pennies,\" the causative agents of subcutaneous and systemic mycosis lead to a granulomatous reaction due to the influx of mononuclear phagocytic cells and a suppurative infiltrate of neutrophils. Treatment of CBM can be challenging as no standard treatment has been established. This case highlights a rare presentation of subcutaneous chromoblastomycosis caused by Rhinocladiella species in the United States with satisfactory management. It emphasizes the role of occupational and exposure history, keeping a high index of suspicion in cases of verrucous nodules or plaques with new satellite lesions on extremities, and recognizing this entity's distinct dermatopathology characteristics.

Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora ( F. monophora ), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.

Chromoblastomycosis (CBM) is a chronic, neglected tropical fungal infection. Its immunopathogenesis, particularly the mechanism underlying its chronicity, remains poorly understood. We performed single-cell RNA sequencing (scRNA-seq) on lesional skin from a CBM patient, followed by comprehensive bioinformatics analyses. We then used multiplex immunofluorescence (mIF) to validate CD4 T cell exhaustion in CBM patient lesions and the mouse model of infection. We identified a significantly expanded population of exhausted CD4 T cells within the patient's lesions, which exhibited high co-expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and functional impairment. Trajectory inference suggested a differentiation path from naive towards exhaustion within the chronic inflammatory environment. Cell-cell communication analysis implicated monocytes/macrophages (MoMacs) as key drivers of this process via persistent antigen presentation and ligand-receptor interactions such as CTLA4-CD80/86 and LGALS9-CD44. The accumulation of exhausted CD4 T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of infection. Our findings establish CD4 T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease.

Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.

Chromoblastomycosis is a chronic fungal infection characterized by the formation of granulomatous lesions in the skin and subcutaneous tissues that begins after inoculation trauma. The disease is more frequently observed in tropical countries such as Brazil. Important studies have been shown a predominantly cell-mediated immune response during chromoblastomycosis. Results from our laboratory showed that Th1 responses are essential to induce protection during chromoblastomycosis. IL-18 is primarily produced by macrophages and is known to induce the production of IFNγ, a cytokine associated with Th1 cell activation. Once produced, IL-18 acts to promote Th1 cell differentiation and activation. Th1 cells, in turn, secrete cytokines such as IFNγ, which are critical for the elimination of intracellular pathogens, including fungi. IFNγ enhances the fungicidal activity of macrophages, promotes the development of antifungal effector mechanisms, and contributes to the containment of fungal growth. Our results indicate that F. pedrosoi is sensed by the NLRP3 inflammasome, which induces caspase-1 activation and production of IL-18. Moreover, IL-18 plays a crucial role in activating Th1 cells and controlling fungal loads during chromoblastomycosis. Further research into the mechanisms underlying IL-18-mediated immunity may lead to the development of novel therapeutic approaches for the treatment of this chronic fungal infection.

Chromoblastomycosis (CBM) is a chronic, progressive, cutaneous and subcutaneous fungal infection following the traumatic implantation of certain dematiaceous fungi. The disease has worldwide prevalence with predominant cases reported from humid tropical and subtropical regions of America, Asia, and Africa. Diagnosis is often delayed or misdirected either due to poor degree of clinical suspicions or clinical simulation of dermatological conditions. The infection is not uncommon in India and several case reports from the sub-Himalayan belt and western and eastern coasts of India have been published; however, very few have reviewed the cases. We reviewed 169 cases published in English literature from India during 1957 through May 2016, including 2 recent cases from our institute. A tremendous increase in the number of reported cases was noticed since 2012, since which, more than 50% of the cases had been published. A majority of the patients (74.1%) were involved in various agricultural activities directly or indirectly. The mean age at presentation was 43.3 years ± 16.0, with male to female ratio of 4.2:1. The duration of disease at the time of presentation varied from 20 days to 35 years. Any history of trauma was recalled only in 33.8% of the studied cases. The lower extremity was the most common site afflicted, followed by the upper extremity. The culture was positive in 80.3% of the cases with Fonsecaea pedrosoi, isolated as the most common fungal pathogen, followed by Cladophialophora carrionii. Although all the commercially available antifungals were prescribed in these cases, itraconazole and terbinafine were the most commonly used, either alone or in combination with other drugs/physical methods, with variable degrees of outcome. Combinations of different treatment modalities (chemotherapy and physical methods) yielded a cure rate of 86.3%. CBM is refractory to treatment and no single antifungal agent or regimen has demonstrated satisfactory results. Increased awareness with early clinical suspicion of the disease and adequate therapy are necessary to improve the outcome. However, depending upon the causative agent, disease severity, and the choice of antifungals, variable outcomes can be observed.

Chromoblastomycosis and phaeohyphomycotic abscesses are infections of the skin and subcutaneous tissues caused by dematiaceous fungi; more rarely, phaeohyphomycotic brain abscesses can occur. The epidemiology and clinical outcomes of chromoblastomycosis and phaeohyphomycotic abscesses are not well-understood in the United States. We used data from the Healthcare Cost and Utilization Project's National Inpatient Sample to obtain yearly national estimates of chromoblastomycosis and phaeohyphomycotic abscess-associated hospitalizations. We examined age group, sex, Census region, season of hospital admission, clinical form of chromoblastomycosis, and presence of selected concurrent conditions. An estimated 690 chromoblastomycosis and phaeohyphomycotic abscess-associated hospitalizations occurred during 2016-2021. Rates were highest in 2016 (0.5/1,000,000) and lowest in 2020 (0.2/1,000,000). Overall, higher hospitalization rates occurred among males (0.4/1,000,000) versus females (0.3/1,000,000). Rates increased with age, with patients aged ≥65 years having the highest rate (0.9/1,000,000). The Northeast had the highest hospitalization rate (0.5/1,000,000) followed by the South (0.4/1,000,000). Hypertension (34%), diabetes (33%), dyslipidemia (28%), and chronic kidney disease (21%) were the most common concurrent conditions. Nine percent had autoimmune inflammatory disease or solid malignancy. Seven percent had solid organ or stem cell transplantation. Subsequently, five percent had lymphedema. Mean hospitalization length was 9.9 days; in-hospital death occurred in 3%. Substantial in-hospital mortality and complications like lymphedema can occur from chromoblastomycosis and phaeohyphomycotic abscesses. Our analysis provides a baseline to monitor hospitalizations and mortality along with comorbidities that may change these outcomes. Public health and clinical partnerships could improve understanding of these fungal diseases caused by dematiaceous fungi through registries, enhanced surveillance, and increased awareness.