RESUMO
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.
Assuntos
Cromoblastomicose , Micetoma , Humanos , Masculino , Cromoblastomicose/patologia , Cromoblastomicose/diagnóstico , Cromoblastomicose/microbiologia , Cromoblastomicose/tratamento farmacológico , Micetoma/patologia , Micetoma/microbiologia , Micetoma/diagnóstico , Micetoma/tratamento farmacológico , Diagnóstico Diferencial , Hospedeiro Imunocomprometido , Hialoifomicose/patologia , Hialoifomicose/microbiologia , Hialoifomicose/diagnóstico , Exophiala/isolamento & purificação , Pessoa de Meia-IdadeAssuntos
Cromoblastomicose , Cladosporium , Humanos , Cladosporium/isolamento & purificação , Cladosporium/genética , Cromoblastomicose/diagnóstico , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Cromoblastomicose/tratamento farmacológico , Masculino , Antifúngicos/uso terapêutico , Pele/patologia , Pele/microbiologiaRESUMO
La cromoblastomicosis es una micosis subcutánea crónica de presentación clínica heterogénea que afecta principalmente a poblaciones de escasos recursos, lo que sumado al acceso limitado a los servicios de salud condiciona el retraso en el diagnóstico y tratamiento, ocasionando secuelas físicas graves. Se describe el caso de un hombre de 50 años con lesiones cutáneas verrugosas y cicatriciales de 30 años de evolución en la extremidad inferior y mano izquierda, además en cara en los últimos cinco años. Se realizó el diagnóstico de cromoblastomicosis de presentación multifocal y clínica mixta, con examen directo e histopatología compatibles, y cultivo para hongos positivo para Fonsecaea pedrosoi. Se indicó tratamiento oral con itraconazol y seguimiento clínico. Reconocer esta entidad es crucial para un diagnóstico y tratamiento oportunos, con el fin de evitar secuelas físicas y estigmatización secundaria. Se debe fortalecer en la atención primaria el reconocimiento de patologías desatendidas y de incidencia subestimada en Colombia, con una presentación multifocal mixta atípica y de un tiempo de evolución prolongado. El examen directo KOH es un herramienta accesible y económica en los primeros niveles de atención que puede contribuir al enfoque diagnóstico.
Chromoblastomycosis is a chronic subcutaneous mycosis with heterogeneous clinical presentation. It mainly affects low-income populations, which added to limited access to health services delays diagnosis and treatment, causing serious physical sequelae. We describe the case of a 50-year-old man with warty and cicatricial skin lesions of 30 years of evolution, at the level of left lower limb and left hand, with face involvement in the last five years. A diagnosis of chromoblastomycosis with multifocal and mixed clinical presentation was made, based on compatible direct examination and histopathology, and positive fungal culture for Fonsecaea pedrosoi. Oral treatment with itraconazole and clinical followup were stablished. Recognizing this entity is crucial for timely diagnosis and treatment, to avoid physical sequelae and secondary stigmatization. Primary health care should be strengthened for the recognition of neglected diseases whose incidence is underestimated in Colombia, with an atypical mixed multifocal presentation and a long evolution time. The KOH direct examination is an accessible and economical tool in the first levels of care that can contribute to the diagnostic approach.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Cromoblastomicose/diagnóstico , Cromoblastomicose/patologia , Doenças NegligenciadasRESUMO
The experimental rodent models for the fungal disease are a handy tool for understanding host-fungus interactions. To Fonsecaea sp., one of the causative agents of chromoblastomycosis, there is an extra challenge because the animals preferably used show a spontaneous cure; so until now, there is no model to reproduce the long-term disease similar to human chronic disease. In this chapter, we described an experimental model using rats and mice with a subcutaneous route, with the checkpoints of acute-like and chronic-like lesion analysis comparable with human lesions, the fungal burden, and the lymphocytes investigation.
Assuntos
Ascomicetos , Cromoblastomicose , Humanos , Camundongos , Ratos , Animais , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Fonsecaea , Modelos Teóricos , Antifúngicos/uso terapêuticoRESUMO
Chromoblastomycosis is a fungal disease presented with local warty papule, plaque, and verrucous nodules. In addition, the incidence and drug resistance of chromoblastomycosis are increasing each year worldwide. Photodynamic therapy is a promising method to treat mycoses. The purpose of this study was to evaluate the effect of new methylene blue (NMB)-induced PDT on multidrug-resistant chromoblastomycosis in vitro. We isolated one wild-type strain pathogen from one clinical patient diagnosed with chromoblastomycosis for over 27 years. The pathogen was identified by histopathology, the morphology of fungal culture, and genetic testing. Drug susceptibility testing was performed on the isolate. It was cultured with logarithmic growth phase spore in vitro and incubated with different concentrations of NMB for 30 min, and received illumination by red light-emitted diode with different light doses. After photodynamic treatment, the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were conducted. The pathogen was Fonsecaea nubica, and it was resistant to itraconazole, terbinafine, amphotericin B, voriconazole andcaspofungin. At the same NMB concentration, the sterilization efficiency of NMB-photodynamic therapy (PDT) on F. nubica increased with increasing light intensity; F. nubica was completely killed at 25 µmol/L NMB with a light dose of 40 J/cm2 or 50 µmol/L NMB and light doses of ≥ 30 J/cm2. SEM and TEM observed ultrastructural changes after PDT. NMB-PDT inactivates the survival of multidrug-resistant F. nubica in vitro; it therefore has the potential to become an alternative or adjuvant treatment for refractory chromoblastomycosis.
Assuntos
Ascomicetos , Cromoblastomicose , Mycobacterium tuberculosis , Humanos , Antifúngicos/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Testes de Sensibilidade MicrobianaRESUMO
Chromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1ß and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1ß, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1ß and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1ß and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.
Assuntos
Cromoblastomicose , Inflamassomos , Humanos , Inflamassomos/metabolismo , Cromoblastomicose/patologia , Caspase 1/metabolismo , Interleucina-18/metabolismo , ApoptoseRESUMO
BACKGROUND: Chromoblastomycosis is a skin infection caused by dematiaceous fungi that take the form of muriform cells in the tissue. It mainly manifests as verrucous plaques on the lower limbs of rural workers in tropical countries. OBJECTIVES: The primary objective of this review is to evaluate the accuracy of diagnostic methods for the identification of chromoblastomycosis, considering the histopathological examination as the reference test. METHODS: MEDLINE, LILACS and Scielo databases were consulted using the terms "chromoblastomycosis" AND "diagnosis". The eligibility criteria were: studies that evaluated the accuracy of tests for the diagnosis of chromoblastomycosis. Eleven studies were selected. Statistical analysis included the calculation of sensitivity and specificity of the diagnostic methods. RESULTS: Considering the histopathological examination as the reference test, the culture showed a sensitivity (S) of 37.5% - 90.9% and a specificity (Sp) of 100%; while direct mycological examination showed S = 50% - 91.6% and Sp of 100% . Considering the culture as the reference test, the serology (precipitation techniques) showed S of 36% - 99%; and Sp of 80% - 100%; while the intradermal test showed S of 83.3% - 100% and Sp of 99.4% - 100%. STUDY LIMITATIONS: The small number of studies and very discrepant sensitivity results among them do not allow the calculation of summary measures through a meta-analysis. CONCLUSIONS: Direct mycological examination, culture, intradermal test and serology show sensitivity and specificity values ââfor the diagnosis of chromoblastomycosis with no significant difference between the studies.
Assuntos
Cromoblastomicose , Cromoblastomicose/diagnóstico , Cromoblastomicose/patologia , Humanos , Técnicas Microbiológicas/métodos , Sensibilidade e EspecificidadeRESUMO
Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous mycosis caused by black, dimorphic, and filamentous fungi of the Herpothrichiellaceae family, such as species of the genus Fonsecaea. These fungi can switch between the saprophytic forms (conidia and hyphae) and the pathogenic form, the muriform cells (MCs), which is considered an essential mechanism for fungal virulence. Nearly all types of cells can produce membranous structures formed by a lipid bilayer that communicate extracellularly with other cells, known as "extracellular vesicles" (EVs), which may act as virulence factors, as observed for several species of pathogenic fungi. Our findings demonstrated for the first time that F. pedrosoi, F. nubica, and F. erecta produce EVs in response to nutritional conditions. The EVs varied in sterol and protein contents, size, and morphology. Moreover, the EVs induced different cytokine and nitric oxide release patterns by bone marrow-derived macrophages (BMDMs). The EVs activated IL-1ß production, possibly acting as the first signal in inflammasome activation. Unlike the pathogenic species, the EVs isolated from F. erecta did not significantly stimulate TNF and IL-10 production in general. Overall, these results demonstrated that different species of Fonsecaea produce EVs capable of modulating pro- and anti-inflammatory cytokine and nitric oxide production by BMDMs and that growth conditions affected the immunomodulatory capacities of the EVs as well as their size, content, and morphology.
Assuntos
Ascomicetos , Cromoblastomicose , Vesículas Extracelulares , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Citocinas , Fonsecaea , Macrófagos , Óxido Nítrico , VirulênciaRESUMO
Deep fungal infections rarely involve the oral cavity and most commonly affect immunocompromised patients. Oral deep fungal infections typically manifest as chronic mucosal ulcerations or granular soft tissue overgrowths. Since these lesions are non-specific and can mimic malignancy, it is crucial to obtain a thorough clinical history and an adequate biopsy to render the appropriate diagnosis. We report four new cases of deep fungal infections, diagnosed as histoplasmosis, blastomycosis and chromoblastomycosis, exhibiting unique oral and perioral presentations. Awareness of these unusual entities can help dental and medical practitioners expedite proper multidisciplinary care and minimize morbidity and mortality.
Assuntos
Blastomicose/patologia , Cromoblastomicose/patologia , Histoplasmose/patologia , Doenças da Boca/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/microbiologiaRESUMO
Chromoblastomycosis (CBM) is a chronic granulomatous fungal infection caused by melanised or brown-pigmented fungi. It can lead to chronic persistent infections and may cause incapacity for labour in some severe clinical forms. The optimal therapy for CBM is still uncertain. Here, we reported the case of a 66-year-old male who has had red plaque and recurrent keratinised protrusions on his right forearm for 20 years. He was treated orally with terbinafine, itraconazole and isotretinoin. He also received carbon dioxide(CO2 ) laser to eradicate the keratinised protrusions and promote the penetration of photosensitiser. After the CO2 laser, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) was adopted immediately to inhibiting the growth of fungi in subcutaneous tissue. The patient received an important improvement with a plaque and crust reduction after 4 months. For such recalcitrant case of chromoblastomycosis, the use of retinoid, CO2 laser combined with ALA-PDT may be a new adjuvant therapy. We further reviewed the cases of chromoblastomycosis treated with laser, photodynamic therapy or retinoic acid.
Assuntos
Antifúngicos/uso terapêutico , Cromoblastomicose/terapia , Fotoquimioterapia/métodos , Retinoides/uso terapêutico , Idoso , Ácido Aminolevulínico/uso terapêutico , Cromoblastomicose/diagnóstico por imagem , Cromoblastomicose/patologia , Humanos , Isotretinoína/uso terapêutico , Itraconazol/uso terapêutico , Lasers , Lasers de Gás/uso terapêutico , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Terbinafina/uso terapêuticoRESUMO
Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecaea pedrosoi. The infection is characterized by erythematous papules and histological sections demonstrating an external layer of fibrous tissue and an internal layer of thick granulomatous inflammatory tissue containing mainly macrophages and neutrophils. Several groups are studying the roles of the innate and adaptive immune systems in F. pedrosoi infection; however, few studies have focused on the role of neutrophils in this infection. In the current study, we verify the importance of murine neutrophils in the killing of F. pedrosoi conidia and hyphae. We demonstrate that phagocytosis and reactive oxygen species during infection with conidia are TLR-2- and TLR-4-dependent and are essential for conidial killing. Meanwhile, hyphal killing occurs by NET formation in a TLR-2-, TLR-4-, and ROS-independent manner. In vivo experiments show that TLR-2 and TLR-4 are also important in chromoblastomycosis infection. TLR-2KO and TLR-4KO animals had lower levels of CCL3 and CXCL1 chemokines and impaired neutrophil migration to the infected site. These animals also had higher fungal loads during infection with F. pedrosoi conidia, confirming that TLR-2 and TLR-4 are essential receptors for F. pedrosoi recognition and immune system activation. Therefore, this study demonstrates for the first time that neutrophil activation during F. pedrosoi is conidial or hyphal-specific with TLR-2 and TLR-4 being essential during conidial infection but unnecessary for hyphal killing by neutrophils.
Assuntos
Cromoblastomicose/imunologia , Fonsecaea/imunologia , Hifas/imunologia , Neutrófilos/imunologia , Esporos Fúngicos/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Cromoblastomicose/genética , Cromoblastomicose/patologia , Camundongos , Camundongos Knockout , Neutrófilos/patologia , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genéticaRESUMO
OBJECTIVE: To describe the clinical aspects of chromoblastomycosis (CBM) presented by patients who had received incomplete antifungal treatment before consultation. METHODS: A prospective study of patients with clinically suspected CBM was performed between 2013 and 2018 in the Department of Dermatology at the University Hospital Antananarivo, and during consultation campaigns. RESULTS: Patients develop CBM over a period of more than 10 years, and many will have already received antifungals prescribed by general practitioners before consulting with a dermatologist. Such treatment obviously modifies the clinical presentation. From the 63 CBM patients in this large study, we describe 12 patients who received oral antifungals (terbinafine, griseofulvine, itraconazole, fluconazole) before consultation. The most frequent clinical aspect presented by these patients was cicatricial lesions, which are characteristically smooth and non-elevated, and enlarge by peripheral extension, with atrophic scarring at the center. CONCLUSION: Our study is the first to show that cicatricial lesions are a clinical aspect presented by CBM patients who received antifungals before presentation.
Assuntos
Antifúngicos/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Adulto , Idoso , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Feminino , Humanos , Itraconazol/uso terapêutico , Madagáscar , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terbinafina/uso terapêuticoRESUMO
Chromoblastomycosis is a cutaneous fungal infection caused by dematiaceous fungi that belong to the order Chaetothyriales and family Herpotrichiellaceae. This infection is prevalent in tropical and subtropical areas and has been designated as a neglected tropical disease according to the WHO. Chromoblastomycosis infection is difficult to treat, and there are limited therapeutic options, making urgent the characterization of new medicines or approaches to treat such infection. In the present case report, two patients with extensive chromoblastomycosis lesions were treated with the combination of itraconazole, acitretin, and imiquimod. In the fourth month of treatment, both patients showed improvement of verrucous plates, suggesting that acitretin combined with drugs already used in chromoblastomycosis therapy can decrease the time of treatment, improving patient's quality of life.
Assuntos
Acitretina/uso terapêutico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/patologia , Imiquimode/uso terapêutico , Itraconazol/uso terapêutico , Acitretina/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Quimioterapia Combinada , Humanos , Imiquimode/administração & dosagem , Itraconazol/administração & dosagem , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Masculino , Pessoa de Meia-IdadeAssuntos
Cromoblastomicose/patologia , Idoso , Antifúngicos/uso terapêutico , Cromoblastomicose/diagnóstico , Cromoblastomicose/tratamento farmacológico , Erros de Diagnóstico , Humanos , Hidróxidos , Indicadores e Reagentes , Itraconazol/uso terapêutico , Leishmaniose Cutânea/diagnóstico , Masculino , Peru , Compostos de Potássio , Tuberculose Cutânea/diagnósticoAssuntos
Cromoblastomicose , Fonsecaea , Melanócitos/patologia , Antifúngicos/uso terapêutico , Cromoblastomicose/diagnóstico , Cromoblastomicose/tratamento farmacológico , Cromoblastomicose/patologia , Diagnóstico Diferencial , Fonsecaea/classificação , Fonsecaea/isolamento & purificação , Mãos/microbiologia , Mãos/patologia , Humanos , Hipertermia Induzida , Inflamação , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/patologia , Patologia Molecular , Vitiligo/diagnóstico , Vitiligo/patologiaRESUMO
Chromoblastomycosis (CBM) is a chronic worldwide subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. It is difficult to treat patients with the disease, mainly because of its recalcitrant nature. The correct activation of host immune response is critical to avoid fungal persistence in the tissue and disease chronification. CD4+ T cells are crucial for the development of protective immunity to F. pedrosoi infection. Here, we investigated T helper cell response dynamics during experimental CBM. Following footpad injection with F. pedrosoi hyphae and conidia, T cells were skewed towards a Th17 and Th1 phenotype. The Th17 population was the main Th cell subset found in the infected area during the early stages of experimental murine CBM, followed by Th1 predominance in the later stages, coinciding with the remission phase of the disease in this experimental model. Depletion of CD25+ cells, which leads to a reduction of Treg cells in the draining lymph node, resulted in decline in fungal burden after 14 days of infection. However, fungal cells were not cleared in the later stages of the disease, prolonging CBM clinical features in those animals. IL-17A and IFN-γ neutralization hindered fungal cell elimination in the course of the disease. Similarly, in dectin-2 KO animals, Th17 contraction in the course of experimental CBM was accompanied by fungal burden decrease in the first 14 days of infection, although it did not affect disease resolution. In this study, we gained insight into T helper subsets' dynamics following footpad injections of F. pedrosoi propagules and uncovered their contribution to disease resolution. The Th17 population proved to be important in eliminating fungal cells in the early stages of infection. The Th1 population, in turn, closely assisted by Treg cells, proved to be relevant not only in the elimination of fungal cells at the beginning of infection but also essential for their complete elimination in later stages of the disease in a mouse experimental model of CBM.
Assuntos
Ascomicetos/imunologia , Cromoblastomicose/imunologia , Lectinas Tipo C/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Modelos Animais de Doenças , Humanos , Hifas , Interferon gama/metabolismo , Interleucina-17/metabolismo , Lectinas Tipo C/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esporos FúngicosRESUMO
Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 µM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 µM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25-2.5 µM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 µM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.