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.

Resazurin to determine the minimum inhibitory concentration on antifungal susceptibility assays for Fonsecaea sp. using a modified EUCAST protocol.

Chromoblastomycosis is a fungal chronic disease, which affects humans, especially in cutaneous and subcutaneous tissues. There is no standard treatment for Chromoblastomycosis, and it is a therapeutic challenge, due natural resistance of their causative agents, inadequate response of patients and common cases of relapse. Protocols for determination of antifungal drugs susceptibility are not standardized for chromoblastomycosis agents and endpoint definition is usually based on visual inspection, which depends on the analyst, making it sometimes inaccurate. We presented a colorimetric and quantitative methodology based on resazurin reduction to resofurin to determine the metabolic status of viable cells of Fonsecaea sp. Performing antifungal susceptibility assay by a modified EUCAST protocol allied to resazurin, we validated the method to identify the minimum inhibitory concentrations of itraconazole, fluconazole, amphotericin B, and terbinafine for eight Fonsecaea clinical isolates. According to our data, resazurin is a good indicator of metabolic status of viable cells, including those exposed to antifungal drugs. This work aimed to test resazurin as an indicator of the metabolic activity of Fonsecaea species in susceptibility assays to antifungal drugs. Species of this genus are the main causative agents of Chromoblastomycosis, which affects humans.

Subcutaneous mycoses: Endemic but neglected among the Neglected Tropical Diseases in Ethiopia.

BACKGROUND: Subcutaneous (deep) mycoses are a chronic infectious disease of the skin and underlying structures endemic in tropical countries. The disease has serious medical and socioeconomic consequences for patients, communities and health services in endemic areas. The inclusion of mycetoma and other subcutaneous mycoses in the list of Neglected Tropical Diseases by WHO highlights the need to assess the burden of these diseases and establish control programs where necessary. In Ethiopia no strategies can be devised because of a lack of epidemiologic information. To address this evidence gap, we performed a national rapid assessment of the geographic distribution of subcutaneous mycoses. METHODOLOGY: We conducted a rapid retrospective assessment using hospital records to identify all suspected and confirmed cases of subcutaneous mycoses in 13 referral hospitals across the country between 2015 and 2022. In each hospital the logbooks were reviewed for diagnoses of subcutaneous mycosess, as diagnosed per routine practice. Descriptive analysis was done. RESULT: From 13 hospitals we extracted 143 cases of subcutaneous mycoses, registered from July 2018 to September 2022. 118 (82.5%) patients were diagnosed as mycetoma, 21 (14.7%) as chromoblastomycosis and the remaining 4 (2.8%) as sporotrichosis. The mean age of patients was 35.8 years (SD = 14.5). 101 (70.6%) patients were male and 96 (67.1%) patients were farmers. 64 (44.8%) cases were from the Tigray regional state. 56 (65.9%) patients had information on diagnostic microscopic evaluation: for mycetoma histopathologic evaluation and fine needle aspiration cytology had a higher positivity rate while for chromoblastomycosis potassium hydroxide (KOH) staining had a better yield. The main clinical presentations were nodules, sinuses and infiltrative plaques on the skin. Radiologic findings of bone involvement was present in some. CONCLUSIONS: Mycetoma and other subcutaneous mycoses are endemic in Ethiopia, with cases reported from almost all regions with the highest cases numbers reported from the northern part of the country. A routine program and systems should be developed to identify and document the burden of subcutaneous fungal infections in the country. Diagnosis and treatment guidelines should be developed.

Subcutaneous phaeohyphomycosis caused by Alternaria section Alternaria.

A woman presented with purulent infiltrating plaques on her hands and arms after a 7-year history of nephrotic syndrome. She was ultimately diagnosed with subcutaneous phaeohyphomycosis, which is caused by Alternaria section Alternaria. The lesions completely resolved after 2 months of antifungal treatment. Interestingly, spores (round-shaped cells) and hyphae were observed in the biopsy and pus specimens, respectively. This case report highlights that distinguishing subcutaneous phaeohyphomycosis from chromoblastomycosis may be difficult if the diagnosis is solely based on pathological findings. It also emphasizes that the parasitic forms of the dematiaceous fungi in immunosuppressed hosts may vary with the site and environment.

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.

New methylene blue-mediated photodynamic inactivation of multidrug-resistant Fonsecaea nubica infected chromoblastomycosis in vitro.

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.

The Role of Excision for Treatment of Chromoblastomycosis: A Cutaneous Fungal Infection Frequently Mistaken for Squamous Cell Carcinoma.

BACKGROUND: Chromoblastomycosis is an uncommon fungal infection of the skin caused by a variety of dematiaceous fungal species that is typically contracted through direct inoculation into the skin. OBJECTIVE: To collect and examine data pertaining to the clinical presentation and management of patients with chromoblastomycosis. METHODS: Through a retrospective study, a pathology medical record search was performed from January 2004 to December 2020 at a single institution. RESULTS: A total of 9 patients were identified. Seven of 9 cases occurred in solid organ transplant recipients. All cases were located on the extremities. Six of 9 cases were clinically suspected to be squamous cell carcinoma. Seven of 9 cases were treated with surgical excision. Six of 9 patients were treated with oral antifungal medication. Four of 9 patients had received combination therapy. Eight of 9 patients had no recurrence of the disease after treatment. CONCLUSION: Chromoblastomycosis presents as verrucous papules or nodules and may clinically and histopathologically mimic squamous cell carcinoma. Immunosuppression is likely a risk factor for the development of chromoblastomycosis. This study highlights the importance of clinical awareness of this disease's clinical presentation and prevalence in immunosuppressed patient populations.

Chromoblastomycosis: A Rare Presentation With Polymorphic Cutaneous Lesions And Bone Involvement, Caused By Exophiala Janselmei.

Chromoblastomycosis, a chronic fungal infection of skin and subcutaneous tissue arises as a result of traumatic inoculation of exposed areas of the body. We present a unique case of chromoblastomycosis caused by Exophiala janselmei in a female farmer who presented with multiple smooth non-tender nodules on trunk and limbs for 5 years and pigmented indurated plaques on her face for 2 years along with deformities of her hands. Imaging investigations revealed multiple lytic lesions in the bones of the upper and lower limbs. Histopathological findings showed characteristic sclerotic bodies, consistent with the diagnosis of chromoblastomycosis. She was started on a combination of oral antifungals with a good response. This case highlights the importance of high suspicion and early diagnosis of deep fungal infections in order to avoid disfigurement and comorbidities.