播散性暗色丝孢霉病患者CARD9突变及相关免疫学研究

暗色丝孢霉病是指由暗色真菌引起的皮肤、皮下组织乃至深部组织脏器的感染。本研究探讨1例由皮肤及皮下组织暗色丝孢霉病逐渐进展为播散性暗色丝孢霉病患者的遗传背景及其抗真菌免疫功能。收集患者10余年病情进展的临床资料及真菌检查结果,进行临床资料及真菌学研究;对外周血DNA采用Sanger测序,进行遗传学研究;提取患者及正常人外周血单个核细胞(peripheral blood mononuclear cell,PBMC),采用蛋白免疫印迹法、流式细胞术、化学发光法、酶联免疫吸附试验等进行免疫学研究。结果显示,患者胱天蛋白酶募集域蛋白9(caspase recruitment domain-containing protein 9,CARD9)基因存在新的复合杂合错义突变(p.R35Q和p.E81K),CARD9蛋白表达正常,外周血淋巴细胞(peripheral blood lymphocyte,PBL)Th1和Th17细胞比例均降低;PBMC抗疣状瓶霉感染存在天然及适应性免疫缺陷。本研究首次报道1例播散性暗色丝孢霉病患者存在CARD9基因新发错义突变,同时发现患者PBMC抗真菌的天然及适应性免疫存在缺陷,提示CARD9蛋白在暗色丝孢霉病发病中可能发挥重要作用。     

Morocco as a possible source for acquisition of Rhinocladiella mackenziei

Rhinocladiella mackenziei cerebral phaeohyphomycosis is a rare severe disease that has been typically described in the Middle East. Here, we report 2 cases of R. mackenziei cerebral phaeohyphomycosis in patients from Morocco, diagnosed and treated in France, and raise a concern about the ever-going extension of the area at risk for this devastating invasive fungal infection.     

Phaeohyphomycosis caused by Alternaria infectoria presenting as multiple vegetating lesions in a renal transplant patient

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy.     

Phialophora verrucosa-induced subcutaneous phaeohyphomycosis. Fine needle aspiration findings

A 34-year-old woman on immunosuppressive therapy presented with a subcutaneous, cystic lesion on the dorsum of the right foot. Cytologic examination of material obtained by fine needle aspiration (FNA) revealed a mixture of acute and granulomatous inflammation as well as brown-pigmented fungi in the form of budding yeast, pseudohyphae and septate hyphae. The findings suggested subcutaneous phaeohyphomycosis (phaeomycotic cyst). Culture grew Phialophora verrucosa. The cytologic, histologic and cultural findings are given. This case demonstrates that phaeohyphomycosis can be diagnosed by FNA but that fungal culture is necessary to establish the identity of the etiologic agent. This appears to be the first case of P. verrucosa-induced subcutaneous phaeohyphomycosis reported in the Western Hemisphere.     

Two new cases of cutaneous alternariosis with a review of the literature

Summary Two cases of cutaneous phaeohyphomycosis due to Alternaria tenuissima in patients affected with primitive myeloproliferative syndrome and lymphocytic lymphoma respectively are reported.Following a review of the specific literature, the authors discuss the etiopathogenic mechanisms, the clinical and histologic aspects of the lesions and the therapeutic problems.     

Subcutaneous phaeohyphomycosis due to Curvularia lunata in a renal transplant patient

BackgroundPhaeohyphomycosis is defined as an infection caused by melanized fungi. It predominates in tropical climate and is currently classified as superficial, allergic, central nervous system or lung infections, and disseminated. Curvularia is one of the many genres which can cause this disease. Phialophora, Alternaria and Exophiala are more commonly isolated from subcutaneous lesions.Case reportA 25-year-old male, renal transplant recipient presents with an ulcer on his left leg. Subcutaneous phaeohyphomycosis due to Curvularia lunata was diagnosed based on mycological examination and histopathological findings. He was successfully treated with systemic itraconazole and surgical resection.ConclusionThe incidence of phaeohyphomycosis has increased in the last decades, especially in immunosuppressed individuals; nevertheless the number of cases does not allow for therapeutic controlled trials to be performed. Hence, we consider that it is important to communicate individual cases and reviews of the literature, to increase awareness of the disease, its clinical presentation and response to treatment.     

Two cases of cutaneous phaeohyphomycosis by Alternaria alternata and Alternaria tenuissima

Two cases of cutaneous phaeohyphomycosis, one with a nodular appearance and the other with an erythematous infiltrating patch, are reported in immunocompromised patients. Diagnosis was based on histological examination, which revealed hyphae and round-shaped fungal cells in a granulomatous dermal infiltrate, and on identification of the moulds when biopsy fragments were cultured on Sabouraud-dextrose agar without cycloheximide. The pathogens were Alternaria tenuissima in the first case and A. alternata in the second. The fungi were examined by scanning electron microscopy. The patients were checked for bone and lung involvement and were then treated with surgical excision and itraconazole, and itraconazole only, respectively, with clinical and mycological resolution. This revised version was published online in August 2006 with corrections to the Cover Date.     

Phaeohyphomicosis by Wangiella dermatitidis in Republic Argentine.

We are presenting the case of a 54 year-old woman, who had a kidney transplant. She came to our laboratory to consult for two cutaneous lesions: a cystic one at the back of her right leg and one localized on dorsum of left forearm. Biopsies of both lesions were performed for a histopathologic study as well as microbiological (both bacteriologic and mycologic) cultures. The histopathologic study showed a lesion compatible with a B type cutaneous lymphoma in the lesion in her leg, while in the mycologic study of the cystic lesion elements compatible with phaeohyphomycosis were observed. Development of Wangiella dermatitidis was obtained in the cultures. The cystic lesion localized on forearm was completely removed by surgery, while the lesion in the leg received oncological treatment. The aim of this paper is to describe the first published case of phaeohyphomycosis, by W. dermatitidis, in the Argentine Republic.     

Chronic Disfiguring Facial Lesions in an Immunocompetent Patient Due to Exophiala spinifera: A Case Report and Review of Literature

Exophiala spinifera is a rare fungus causing chromoblastomycosis or different types of phaeohyphomycosis (cutaneous, subcutaneous, disseminated and cyst phaeohyphomycosis). We report a case of a young male with phaeohyphomycosis due to E. spinifera, who had multiple itchy painful papular lesions disfiguring his face for 4?years. His diagnosis was delayed and had received antibacterial and antileishmanial therapy elsewhere without any improvement. While he reported to our hospital, the histopathology of the biopsy collected from the lesion demonstrated acute on chronic inflammation with granuloma formation and darkly pigmented fungal elements. The isolate grown on culture was identified as E. spinifera on the basis of morphological characters. The identification of the isolate was further confirmed by sequencing of the ITS region of ribosomal DNA. After treatment with oral itraconazole, he had marked clinical improvement.     

Cutaneous and Mucosal Phaeohyphomycosis Caused by Exophiala spinifera in a Pregnant Patient: Case Report and Literature Review

We report a case of mucocutaneous phaeohyphomycosis caused by Exophiala spinifera. Crusty plaques and nodules were major clinical features. Histological examination revealed brown yeast-like cells and hyphae. Mycological and molecular data identified E. spinifera as etiologic agent. Oral itraconazole was effective, which was in accordance with the results of in vitro susceptibility testing. We speculated that her pregnancy may play a role of risk factor in the infection by E. spinifera.     

The First Case of Phaeohyphomycosis Caused by Rhinocladiella basitona in an Immunocompetent Child in China

We present the first case of phaeohyphomycosis caused by Rhinocladiella basitona (R. basitona) in China and describe the mycological characteristics of this pathogen. A 11-year-old girl was presented with plaque on her face for 3 years. Diagnosis was based on histopathology, mycology, and molecular identification. The patient was treated with terbinafine and itraconazole. This case is the second of phaeohyphomycosis caused by R. basitona in the world (previously belonging to Geniculosporium).     

Generalized Subcutaneous Phaeohyphomycosis Caused by Phialophora verrucosa: Report of a Case and Review of Literature

We report a case of subcutaneous phaeohyphomycosis due to Phialophora verrucosa in a 64-year-old Chinese farmer suffering from CD4+ lymphopenia. He presented with diffuse and infiltrated plaques involving the entire face including the eyes, neck, occiput, and extending to the dorsal regions of his torso. The patient is notable for the discrete multifocal nature of the illness in the absence of disseminated infection and rarity of P. verrucosa as a cause of subcutaneous phaeohyphomycosis.     

Neutrophil Extracellular Traps Serve as Key Effector Molecules in the Protection Against Phialophora verrucosa

Mycopathologia - Phialophora verrucosa (P. verrucosa) is a pathogen that can cause chromoblastomycosis and phaeohyphomycosis. Recent evidence suggests that neutrophils can produce neutrophil...     

Wangiella dermatitidis isolated from bats in Manaus Brazil

Wangiella dermatitidis was isolated for the first time from the macroscopically asymptomatic internal organs of 2 Phyllostomus discolor, 1 Molossus molossus, 1 Sturnira lilium and 1 Myotis albescens among bats captured in the region of Manaus, Brazil. The dermatiaceous fungi isolated exhibited polymorphism at 25 and 37 degrees C, showing toruloid hyphae, integrated and terminal phialides without collarettes and yeast-like cells. The fungi did not hydrolyze gelatin, casein or starch. Some ecological aspects of bats in relationship to the epidemiology of phaeohyphomycosis are discussed.     

Report of chronic subcutaneous abscesses caused byExophiala spinifera

A case of phaeohyphomycosis with subcutaneous abscesses involving skin, muscle and bone was caused byExophiala spinifera. This is the first report ofE. spinifera causing bone degeneration in Recife-PE, Brazil.     

Application of flow cytometry to differentiating Exophiala dermatitidis E. moniliae and E. jeanselmei from each other

We applied a flow cytometry apparatus (FCM) to differenciating Exophiala dermatitidis, E. moniliae and E. jeanselmei from each other. The wavelength of the argon laser emitted from the FCM was 488 nm and the aperture of nozzle from which the stream of fluid containing single cells was blown out was 100 m. By irradiating the stream with laser by either the forward light scatter (FLS) or by the perpendicular light scattr (PLS), we were able to get two pieces of informations. Histograms displayed by the FLS indicate the cell size, while dot displays by the PLS reflect the cell structure. As a result, E. dermatitidis was clearly differenciated from either E. moniliae or E. jeanselmei by their histograms by FLS. In addition, dot displays by the PLS differenciated E. moniliae from E. jeanselmei.In conclusion, flow cytometry is available for differenciating E. dermatitidis, E. moniliae and E. jeanselmei from each other.     

Disseminated Phaeohyphomycosis Caused by Curvularia tuberculata in a Previously Healthy Man

Mycopathologia - Disseminated phaeohyphomycosis is an extremely rare clinical syndrome, especially in a host without apparent immunological defect. Here, we report a case of disseminated...     

Successful Terbinafine Treatment for Cutaneous Phaeohyphomycosis Caused by Trematosphaeria grisea in a Heart Transplanted Man: Case Report and Literature Review

Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.

     

Cutaneous Phaeohyphomycosis of the Right Hand Caused by Exophiala jeanselmei: A Case Report and Literature Review

Mycopathologia - Exophiala spp. is increasingly reported as a pathogen causing the cutaneous, subcutaneous or invasive infection. In this report, we present a case of cutaneous phaeohyphomycosis...