Nodular lesions of the buttock for 20 years: the challenge of chromoblastomycosis in non-endemic settings.

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.

An Experimental Model of Chromoblastomycosis Caused by Fonsecaea sp. Species.

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.

Pathogenicity and Growth Conditions Modulate Fonsecaea Extracellular Vesicles' Ability to Interact With Macrophages.

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.

Cromoblastomicosis: primer caso alóctono tratado en Chile / Chromoblastomycosis: first allochthonous case treated in Chile

Resumen La cromoblastomicosis es una infección fúngica de la piel y del tejido subcutáneo, de evolución crónica, causada por hongos dematiáceos que se caracterizan por presentar melanina en su pared celular. La enfermedad se presenta en todo el mundo, principalmente en regiones tropicales y subtropicales. En Chile, solo hay un reporte de caso humano hace más de 30 años. Se presenta el caso de un varón de 46 años, haitiano, residente en Chile, con placas verrucosas en la zona tibial anterior de un año de evolución. El diagnóstico de cromoblastomicosis se confirmó al observar células muriformes en la histopatología y colonias dematiáceas en el cultivo micológico; además, en la miscroscopía directa se observaron conidias compatibles con Fonsecaea spp. Luego de seis meses de tratamiento con antimicóticos sistémicos y crioterapia, se logró la remisión completa de las lesiones.

Abstract Chromoblastomycosis is a fungal infection of the skin and subcutaneous tissue, of chronic evolution, caused by dematiaceous fungi. The disease occurs worldwide, mainly in tropical and subtropical regions, but in regions like Chile there is only one report of a human case more than 30 years ago. We present the case of a 46-year-old Haitian man, resident in Chile, with verrucous plaques in the right anterior tibial area of one year of evolution. The diagnosis of chromoblastomycosis was confirmed when muriform cells and dematiaceous colonies were observed in the histopathological analysis and the direct microscopy, respectively. After six months of treatment with systemic antimycotics and cryotherapy, complete remission of the lesions was achieved.

Cyphellophora laciniata: A new etiological agent of chromoblastomycosis.

Chromoblastomycosis is a chronic subcutaneous mycosis caused by traumatic inoculation of dematiaceous fungi especially in tropical and subtropical areas. Cyphellophora genus include melanized fungi reported as etiological agents of skin and nail infections. We report a 60-year-old male from the south of Mexico with a 40-year history of chromoblastomycosis caused by Cyphellophora laciniata. The isolated fungus was identified by sequencing of the internal transcribed spacer region of rDNA. The patient was treated with itraconazole and cryosurgery with unsatisfactory results.

Chromoblastomycosis by Exophiala jeanselmei associated with squamous cell carcinoma.

Chromoblastomycosis is a subcutaneous, chronic, granulomatous mycosis that occurs more frequently in tropical and subtropical countries. Herein, we describe a case of a 90-year-old female patient with diagnosis of chromoblastomycosis by Exophiala jeanselmei with a 22-year evolution who developed a squamous cell carcinoma. In the meantime, She underwent two misdiagnoses and an unnecessary operation. This case is also the fifth case of E. jeanselmei caused CBM in history.

Diagnóstico microbiológico en un paciente con cromomicosis / Microbiological diagnosis in a patient with chromomycosis

RESUMEN La cromomicosis es una micosis subcutánea; uno de los pilares para su diagnóstico certero son los resultados de los estudios microbiológicos. Se presenta el caso de un hombre campesino, que tenía, desde hacía ocho años, lesiones papulares que evolucionaron a placas verrugosas y escamosas en el antebrazo izquierdo. El examen directo micológico de las escamas, así como su cultivo, apoyaron el diagnóstico de una cromomicosis. En la microscopía de su forma de esporulación se identificó al agente etiológico: fonsecaea pedrosoi. Este hallazgo resultó novedoso pues hacía más de una década que no se diagnosticaba ni se informaba un caso de cromomicosis en el laboratorio. La promoción y prevención de salud es un pilar fundamental en el sistema de salud, ya que mediante la educación del campesinado cubano se puede prevenir esta enfermedad, disminuir los costos médicos, curar oportunamente, y mejorar la calidad de vida de los campesinos.

ABSTRACT Chromomycosis is a subcutaneous mycosis; the results of microbiological studies are one of the pillars for its accurate diagnosis. A male farmer who had, for eight years, papular lesions that evolved to warty and scaly plaques on the left forearm is presented. The direct mycological examination of the scales, as well as their culture, supported the diagnosis of a chromomycosis. The etiological agent Fonsecaea pedrosoi was identified in the microscopy of its sporulation form. This finding was novel since a case of chromomycosis had not been diagnosed or reported in the laboratory for more than a decade. Health prevention and promotion is a fundamental pillar in the health system, since through the education of the Cuban farmers this disease can be prevented, medical costs can be reduced, timely cures and the quality of life of the farmers can be improved.

An optimized Agrobacterium tumefaciens-mediated transformation system for random insertional mutagenesis in Fonsecaea monophora.

Chromoblastomycosis (CBM) is a chronic cutaneous or subcutaneous mycosis that is prevalent worldwide. Though CBM tends not to be fatal, it is difficult to treat and complications can include chronic, marked lesions, lymphatic damage, and neoplastic transformation. Fonsecaea monophora, as a new species segregated from Fonsecaea pedrosoi, is the predominant causative pathogen of CBM in southern China. However, research about F. monophora has been limited, which may be due to a lack of an effective genetic manipulation system for F. monophora. In this study, we successfully established a random insertional mutagenesis system by Agrobacterium tumefaciens-mediated transformation (ATMT) in F. monophora for the first time. In order to improve the efficiency of ATMT, various co-culture conditions were optimized, including: acetosyringone (AS) concentrations, co-culture duration, ratio of bacteria to conidia, and the A. tumefaciens strains. In addition, thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR) was performed to identify the transferred DNA (T-DNA) flanking sequences of the F. monophora transformants. The valuable transformants obtained in this study will be used for research in the future.

5-aminolevulinic acid-based photodynamic therapy associated with Itraconazole successfully treated a case of chromoblastomycosis.

Chromoblastomycosis (CBM) is a prevalent implantation fungal infection. Patients with CBM show chronic granulomatous hyperplasia with ulcers and exudation. It may cause incapacity for labor in some severe clinical forms and it is often refractory to antifungal therapies. There is no optimal treatment. Here we report a case of a 71-year-old male farmer with refractory CBM who was successfully treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and Itraconazole in 2 months. Clinical cure was achieved with no obvious side effects.

Chromoblastomycosis caused by Rhinocladiella aquaspersa: first case report in Guatemala.

The authors report a case of 40-year-old male patient with a five-year history of chromoblastomycosis on his right leg. Diagnosis was performed by direct 40% KOH exam of skin scales, culture with micro- and macromorphologic analysis, and genotypic characterization (sequencing of a fragment of the ITS region and phylogenetic analysis) of the isolated fungus. Rhinocladiella aquaspersa was identified as the etiological agent. Initially, the treatment was with oral itraconazole 200mg/day for one year. However, the presence of "sclerotic cells" with filaments ("Borelli spiders") resulted in a change of medical treatment: a higher dose of itraconazole (400mg/day) and surgery, achieving clinical and mycological cure in one year. This is the first report of chromoblastomycosis caused by R. aquaspersa in Guatemala.

Chromoblastomycosis caused by Rhinocladiella aquaspersa: first case report in Guatemala

Abstract The authors report a case of 40-year-old male patient with a five-year history of chromoblastomycosis on his right leg. Diagnosis was performed by direct 40% KOH exam of skin scales, culture with micro- and macromorphologic analysis, and genotypic characterization (sequencing of a fragment of the ITS region and phylogenetic analysis) of the isolated fungus. Rhinocladiella aquaspersa was identified as the etiological agent. Initially, the treatment was with oral itraconazole 200 mg/day for one year. However, the presence of "sclerotic cells" with filaments ("Borelli spiders") resulted in a change of medical treatment: a higher dose of itraconazole (400 mg/day) and surgery, achieving clinical and mycological cure in one year. This is the first report of chromoblastomycosis caused by R. aquaspersa in Guatemala.

[Fonsecaea pedrosoi-induced chromoblastomycosis: about a case]. / Chromomycose cutanée à Fonsecaea Pedrosoi: à propos d'un cas.

We report the case of a 13-year old female patient from rural areas presenting with papulonodular lesion of 4/3cm in the lower third of the right leg, evolving over the last two years. Skin biopsy showed papillomatous hyperplasia with neutrophilic microabscess and spores. Direct mycological examination showed fumagoid bodies and Fonsecaea pedrosoi was isolated from culture. The patient underwent medico-surgical treatment (terbinafine 250mg/day for 6 months + resection and then skin graft) with good evolution and a follow-up period of 2 years without recurrences. Chromoblastomycosis is a chronic fungal skin infection, common in tropical and subtropical areas and rare in North Africa. In Morocco, only seven cases have been reported in the literature until June 2014. It is contracted from inoculation of germ after contact with the soil or organic matters. Responsible officers are pigmented fungi belonging to the dematiated group. Given its rarity, it can mimic other dermatoses such as leishmaniasis or tuberculosis. Despite the rarity of this infection, clinicians should suspect it in patients with chronic skin lesions (verrucous, vegetative, nodular and grouped in patches), especially if they occur in areas exposed to potential plant injuries, such as the lower limbs. Mycological examination is necessary to confirm the diagnosis. Surgery or the association between surgery and systemic antifungal drugs are the treatments of choice because antifungal drugs alone may result in resistances or recurrences.

Chromoblastomycosis: an etiological, epidemiological, clinical, diagnostic, and treatment update.

Chromoblastomycosis is a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue caused by traumatic inoculation of dematiaceous fungi of the family Herpotrichiellaceae. The species Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in regions where the disease is endemic. Chromoblastomycosis lesions are polymorphous: verrucous, nodular, tumoral, plaque-like, and atrophic. It is an occupational disease that predominates in tropical and subtropical regions, but there have been several reports of cases in temperate regions. The disease mainly affects current or former farm workers, mostly males, and often leaving disabling sequelae. This mycosis is still a therapeutic challenge due to frequent recurrence of lesions. Patients with extensive lesions require a combination of pharmacological and physical therapies. The article provides an update of epidemiological, clinical, diagnostic, and therapeutic features.

Chromoblastomycosis: an etiological, epidemiological, clinical, diagnostic, and treatment update

Abstract: Chromoblastomycosis is a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue caused by traumatic inoculation of dematiaceous fungi of the family Herpotrichiellaceae. The species Fonsecaea pedrosoi and Cladophialophora carrionii are prevalent in regions where the disease is endemic. Chromoblastomycosis lesions are polymorphous: verrucous, nodular, tumoral, plaque-like, and atrophic. It is an occupational disease that predominates in tropical and subtropical regions, but there have been several reports of cases in temperate regions. The disease mainly affects current or former farm workers, mostly males, and often leaving disabling sequelae. This mycosis is still a therapeutic challenge due to frequent recurrence of lesions. Patients with extensive lesions require a combination of pharmacological and physical therapies. The article provides an update of epidemiological, clinical, diagnostic, and therapeutic features.

[Extensive cutaneous chromomycosis: Efficacy of combined terbinafine and cryotherapy]. / Chromomycose cutanée étendue : efficacité de l'association terbinafine et cryothérapie.

BACKGROUND: Chromomycosis is a chronic fungal skin infection, mainly affecting the limbs. It is responsible for severe morbidity and its treatment remains long and disappointing. Rarely described in Morocco, we report a new observation that has evolved very well under treatment combining terbinafine and cryotherapy over a short duration. CASE REPORT: A 56-year-old patient, immunocompetent, had a pustular and crusty placard on both forearms that had evolved for a year. Mycological examination showed fumagoid bodies and cutaneous biopsy showed epithelioid granulomas and giant cells without necrosis. The PCR confirmed a chromomycosis at Fonsecaea pedrosoi. HIV serology was negative. Treatment with terbinafine 250mg/d for 6months combined to cryotherapy resulted in complete remission with initial clinical improvement after only 3 weeks. DISCUSSION: Chromomycosis occurs increasingly in non-tropical areas. If diagnostic methods become more effective, management remains difficult and poorly codified. Terbinafine-cryotherapy combination would bring a lot of benefits with a little risk to bothpractitioner and patient. CONCLUSION: This combined treatment would constitute an excellent therapeutic alternative because of its efficiency, feasibility, low cost, method of administration and aesthetic result.

Endobronchial Topical Amphotericin B Instillation for Pulmonary Chromomycosis After Lung Transplantation: A Case Report.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

From phaeohyphomycosis to disseminated chromoblastomycosis: A retrospective study of infections caused by dematiaceous fungi.

OBJECTIVE: Infections caused by dematiaceous fungi are more common in tropical and subtropical areas. We aimed to describe the clinical, microbiological and therapeutic aspects of case patients diagnosed at a University Hospital located on an Indian Ocean island. PATIENTS AND METHODS: We performed an observational retrospective study of infections caused by dematiaceous fungi diagnosed at the University Hospital of Saint-Pierre, Reunion, from 2000 to 2015. Mycological identifications were performed at the National Reference Center for Invasive Mycosis and Antifungal Agents (Paris). RESULTS: The review of clinical and microbiological data of 11 patients identified revealed that five were infected by dematiaceous fungi. Two had cutaneous phaeohyphomycosis, two had cerebral phaeohyphomycosis and one had cutaneous chromoblastomycosis with brain and potentially medullary dissemination. Skin lesions and cerebral abscesses were quite varied. CONCLUSION: Infections caused by dematiaceous fungi are rare. Medullary and brain localizations are extremely rare, especially for chromoblastomycosis. Cutaneous manifestations of phaeohyphomycosis are varied; diagnosis is thus more difficult. It is therefore important, when confronted with a chronic tumor-like lesion in endemic areas, to perform a biopsy for pathology and fungal culture. While surgical excision is not always sufficient, medical treatment of these infections is not standardized, but relies on an azole, which can be associated with another antifungal agent.

Chromoblastomycosis: tissue modifications during itraconazole treatment.

BACKGROUND:: Histological and mycological changes during itraconazole use have not been totally established in chromoblastomycosis. OBJECTIVES:: To evaluate tissue modifications in chromoblastomycosis carriers under itraconazole treatment. METHODS:: A histological retrospective study of 20 cases of chromoblastomycosis seen at the university hospital at the south of Brazil, during itraconazole 400 mg daily treatment. Patients were classified into two groups: plaque or tumor lesions, and underwent periodic evaluations every four months during three years. Hematoxylin-eosin stain was used to analyze epidermal modifications, inflammatory infiltrate and fibrosis, and Fontana-Masson stain for parasite evaluation. RESULTS:: Fontana-Masson stain was superior to hematoxylin-eosin stain in fungal count in the epidermis (mean difference=0.14; p<0.05). The most distinct mycosis tissue responses were registered in the dermis. Epidermal thinning, granulomatous infiltrate decrease or disappearance, fibrosis increase and quantitative/morphological changes occurred during treatment. STUDY LIMITATIONS:: Patients could not be located to have their current skin condition examined. CONCLUSION:: Parasitic and tissue changes verified in this study can reflect the parasite-host dynamics under itraconazole action.