Combination therapy with itraconazole and terbinafine for phaeohyphomycosis caused by Exophiala spinifera: A case report and literature review.

Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.

Multifocal cutaneous phaeohyphomycosis caused by Exophiala spinifera with clinical resolution in an immunocompromised cat.

Case summary: A 3-year-old neutered domestic shorthair cat with a long history of idiopathic immune-mediated haemolytic anaemia and thrombocytopenia treated with ciclosporin and prednisolone was referred 2 months after the appearance of nodular dermatitis. A single pigmented nodule was present in the lateral carpal region of the right foreleg. The lesion was 7 mm in diameter, non-exudative and cutaneous to subcutaneous. Fine-needle aspiration of the mass revealed the presence of pigmented fungal elements. Excisional surgery was planned; in the meantime, a plaque-like lesion developed in the interorbital region. Histopathological examination confirmed the presumptive diagnosis of phaeohyphomycosis, and Exophiala spinifera was identified as the aetiological agent. Itraconazole, given orally at a dose of 10 mg/kg for 8 weeks following surgery, enabled clinical resolution despite continued use of immunosuppressants. The follow-up was carried out over 14 weeks. Relevance and novel information: This case report provides the first evidence of multifocal cutaneous phaeohyphomycosis caused by E spinifera with clinical resolution after combined surgical and itraconazole treatment in an immunocompromised cat.

Peritoneal dialysis-associated peritonitis caused by Exophiala spinifera: A case report and review of literature.

Exophiala spinifera is a black ascomycetous yeast and is responsible for phaeohyphomycosis. We provide the first case report of peritoneal dialysis (PD)-associated peritonitis in a female patient with progressive impairment of visual capacity. The infection was caused by a cutaneous infection of her hands. The patient responded well with PD catheter removal and 2-week antifungal medication. This case emphasizes the importance of hand hygiene and regular eye evaluation in preventing environment-bound infection in patients on PD. 2012 Elsevier Ltd. All rights reserved.

Inherited CARD9 Deficiency in a Patient with Both Exophiala spinifera and Aspergillus nomius Severe Infections.

PURPOSE: Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary Aspergillus infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency. MATERIALS AND METHODS: Genetic analysis was performed by Sanger sequencing. Neutrophils and mononuclear phagocyte response to fungal stimulation were evaluated through luminol-enhanced chemiluminescence and whole blood production of the proinflammatory mediator interleukin (IL)-6, respectively. RESULTS: We report a 56-year-old Argentinean woman, whose invasive Exophiala spinifera infection at the age of 32 years was unexplained and reported in year 2004. At the age of 49 years, she presented with chronic pulmonary disease due to Aspergillus nomius. After partial improvement following treatment with caspofungin and posaconazole, right pulmonary bilobectomy was performed. Despite administration of multiple courses of antifungals, sustained clinical remission could not be achieved. We recently found that the patient's blood showed an impaired production of IL-6 when stimulated with zymosan. We also found that she is homozygous for a previously reported CARD9 loss-of-function mutation (Q289*). CONCLUSIONS: This is the first report of a patient with inherited CARD9 deficiency and chronic invasive pulmonary aspergillosis (IPA) due to A. nomius. Inherited CARD9 deficiency should be considered in otherwise healthy children and adults with one or more invasive fungal diseases.

Phaeohyphomycosis due to Exophiala spinifera greatly improved by ALA-PDT: A case report.

An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection.

Exploration of insecticidal potential of an alpha glucosidase enzyme inhibitor from an endophytic Exophiala spinifera.

AIM: The present study aimed to isolate and screen endophytes from Trachyspermum ammi with the ability to inhibit alpha glucosidase enzyme and evaluate their insecticidal potential. METHODS AND RESULTS: Endophytic fungi isolated from T. ammi were screened for alpha glucosidase inhibitory activity. Maximum inhibition (96%) was observed in an isolate AZ-9, identified to be Exophiala spinifera on morphological and molecular basis. Production of fungal metabolites was carried out in malt extract broth followed by extraction with ethyl acetate. Brown coloured gummy residue obtained after evaporation of ethyl acetate was partially soluble in water yielding white precipitates. The precipitate exhibiting α-glucosidase inhibitory activity was purified by repeated washing and centrifugation. The insecticidal activity of inhibitor was evaluated on Spodoptera litura (Fab.) by feeding this pest on diet amended with inhibitor. It resulted in significant larval mortality as well as deformities in emerging adults. A reduction in vivo digestive enzyme activity was also observed. Nutritional analysis revealed the toxic effect of AZ-9 inhibitor on various food utilization parameters of S. litura. A significant reduction was recorded in relative growth and consumption rate of S. litura. CONCLUSIONS: This is the first report on production of an alpha glucosidase inhibitor from E. spinifera with insecticidal activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights the importance of endophytes in providing protection against insect pests to the host. It also suggests the insecticidal potential of alpha glucosidase inhibitor from E. spinifera against polyphagous pest S. litura.

Multifocal but non-disseminated phaeohyphomycosis in a healthy man via a unique mechanism: Ejection from motor vehicle accident into a vegetable field in Afghanistan resulting in multiple contaminated skin wounds.

A 20-year-old male presented with multiple subcutaneous nodules on the head, neck, chest and oral cavity. FNA and biopsy showed pigmented fungal hyphae diagnostic of multifocal phaeohyphomycosis, found to be Exophiala spinifera by molecular diagnostics. The presentation initially raised concern for disseminated disease and occult immunosuppression. However, the patient appeared to be immunocompetent and otherwise healthy. Upon further inquiry, the patient was in a motor vehicle accident 4 years before presentation; he was ejected into a vegetable field resulting in multiple open wounds. Multifocal phaeohyphomycosis usually indicates disseminated systemic disease from immunosuppression and carries a grave prognosis.

Subcutaneous phaeohyphomycosis caused by Exophiala spinifera in a European patient with lymphoma: a rare occurrence case report and literature review.

Exophiala spinifera is a dematiaceous fungus responsible for rare skin infections presenting as phaeohyphomycosis or chromoblastomycosis which has been primarily reported in tropical and subtropical areas (Asia, South and North America). We report the first case of E. spinifera phaeohyphomycosis in a European patient. The phaeohyphomycosis was limited to the skin, involving the finger of an immunocompromised patient presenting with a large B-cell lymphoma treated by R-mini-CHOP regimen. Remission was initially achieved by surgical excision; however, a local subcutaneous relapse required treatment with itraconazole. We performed a literature review of the 32 previously published cases of E. spinifera phaeohyphomycosis highlighting its clinical phenotype: disseminated infection with extracutaneous involvement and poor prognosis were reported in young patients, of whom some were recently associated with CARD9 mutations, whereas cases in older immunocompromised patients were limited to the skin and showed better prognosis. There is currently no standard treatment for E. spinifera phaeohyphomycosis; however, itraconazole, alone or in combination, allowed partial or complete response in 16 out of 20 cases.

Chromoblastomycosis Associated with Bone and Central Nervous Involvement System in an Immunocompetent Child Caused by Exophiala Spinifera.

Chromoblastomycosis is a chronic granulomatous infection of the skin and subcutaneous tissue caused by specific group of dematiaceous fungi. The infection results from traumatic injury and is seen more commonly on feet and lower legs. It is rarely seen in children and metastatic spread to other systems is exceptionally rare. We report a 12-year-old immunocompetent male child diagnosed with chromoblastomycosis on the lower leg, who in a span of few months developed osteomyelitis and left hemiparesis. Fungal culture showed growth of Exophiala spinifera. Child showed good improvement with voriconazole and itraconazole after 1 year of treatment. Skin lesions healed with minimal scarring and his power improved.

Phaeohyphomycosis caused by Exophiala spinifera: an increasing disease in young females in mainland China? Two case reports and review of five cases reported from mainland China.

No more than 30 cases of phaeohyphomycosis caused by Exophiala spinifera have been reported up to now in English and Chinese literature over the past half century. Here, we reported two cases of phaeohyphomycosis caused by E. spinifera and reviewed all the five cases reported from mainland China. These two involved were both young female, one patient experiencing recurrence during pregnancy and the other developing multiple-site infections without apparent immunodeficiency. The aetiological agents were both identified as E. spinifera by molecular analysis. Oral itraconazole was proved effective enough for the first patient, while the combination of itraconazole and terbinafine was needed for the second patient. It seems that infections due to E. spiniferais increasing in China mainland nowadays, usually involving young female.

In vitro susceptibility of chromoblastomycosis agents to five antifungal drugs and to the combination of terbinafine and amphotericin B.

Chromoblastomycosis is a chronic mycosis that affects the skin and subcutaneous tissues caused by several genera of dematiaceous fungi. There is not a treatment of choice. Thus, tools that help guide clinical practice are fundamental. In this sense, antifungal activity tests in vitro could be useful. However, trials with chromoblastomycosis agents are scarce. The aim of this study was to evaluate both the in vitro susceptibility of 60 chromoblastomycosis agents to five antifungals and the combination of amphotericin B (AMB) and terbinafine (TRB). TRB, itraconazole (ITZ) and ketoconazole (KTZ) were, in this order, the drugs which showed better activity against the chromoblastomycosis agents. The less active drugs were voriconazole (VRZ) and AMB. The more differentiated group was Exophiala spinifera. Cladophialophora carrionii and Fonsecaea spp. are significantly more susceptible to KTZ than Phialophora verrucosa, whereas C. carrionii is significantly more sensitive to VRZ than P. verrucosa and E. spinifera. Assays in this direction allow the knowledge of the susceptibility of the causative agents which may help the management of patients with this disease. This study includes the largest number of these agents and of genera found in the literature.

Phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus / 中华皮肤科杂志

A 27-year-old woman who suffered from a 2-year history of systemic lupus erythematosus (SLE) presented with a 6-month history of nodules and ulcer on the right lower extremity. Direct microscopic examination of the pus showed branched and septate hyphae and spores in a chain-like arrangement.Histopathological examination revealed yellowish brown hyphae and spores. Dark green velvety colony grew on Sabouraud dextrose agar (SDA). Slide culture showed branched, septate hyphae and spine-like annellated conidiophores. The isolate was identified as Exophiala spinifera by DNA sequence analysis. The strain was unable to liquefy gelatin, could grow at 25 ℃ to 39 ℃, and was sensitive to itraconazole, amphotericin B and terbinafine. Animal test revealed that the infection induced by Exophiala spinifera in immunocompromised mice was more severe than that in normal controls. Based on the clinical features, histopathological, fungal culture and DNA sequencing results, the patient was diagnosed with systemic lupus erythematosus accompanied by subcutaneous phaeohyphomycosis caused by Exophiala spinifera.