播散型组织胞浆菌病研究进展

组织胞浆菌病是由组织胞浆菌引起的深部真菌疾病。播散型组织胞浆菌病为所有临床分型中最为凶险的类型,其特点为起病急、发展快、死亡率高,诊断及治疗也颇为棘手。该病既往被认为是一种地方流行性疾病,多见于美国中西部等西半球地区,我国少见且多为输入性病例。但现阶段我国本土病例也屡有报道,故本文在复习相关文献基础上总结了播散型组织胞浆菌病的流行病学现状、易感人群、临床表现、诊断方法及治疗进展,以飨读者。     

皮肤播散型孢子丝菌病1例并文献复习

目的探讨皮肤播散型孢子丝菌病发生的病因、临床特点、诊断及鉴别诊断,以提高对该病的认识,避免误诊、误治。方法对1例以声嘶为首发表现的皮肤播散型孢子丝菌病的临床资料、组织病理、真菌培养结果进行分析,并进行相关文献复习。结果患者以声嘶为首发表现,3个月后出现全身散在皮下结节。结节逐渐增多,部分破溃伴脓血。咽部组织病理示鳞状上皮黏膜急慢性炎伴上皮乳头状增生,可见多核巨细胞,抗酸染色未查出阳性菌。皮损处脓液真菌镜检及培养阴性。病理符合感染性肉芽肿。组织真菌培养见孢子丝菌生长。诊断为皮肤播散型孢子丝菌病。结论皮肤播散型孢子丝菌病在免疫正常人群发病时容易导致误诊误治;皮损表面脓液真菌镜检及培养阳性率低。病变组织真菌培养有利于得到阳性结果,早日明确诊断和治疗。     

造血干细胞移植治疗恶性血液病合并播散性镰刀菌病4例临床分析并文献复习

目的提高对造血干细胞移植患者合并镰刀菌感染,尤其是播散性镰刀菌病的认识,以做到早期诊断、及时治疗,从而改善其预后。方法对本院从2015年4月至2020年9月诊治的4例造血干细胞移植患者合并播散性镰刀菌病的诊断、治疗及预后进行回顾性分析。结果 4例患者均为确诊病例,均发生于造血干细胞植活前或粒缺期,给予两性霉素B脂质体/两性霉素B联合伏立康唑抗真菌治疗。3例患者的播散性镰刀菌病得到控制(其中1例死于铜绿假单胞菌败血症),1例抗真菌治疗后无效死亡。结论造血干细胞移植后播散性镰刀菌病预后差,死亡率高,早期给予有效抗真菌治疗及快速免疫重建是改善其生存率的有效手段。     

镰刀菌感染的流行病学及其诊治进展

镰刀菌是一种腐生菌,与免疫力正常宿主的软组织感染、角膜炎、甲真菌病有关。由于应用细胞毒性药物治疗白血病以及器官移植增多,侵袭性和播散性镰刀菌感染病例近20年内逐年增多。镰刀菌可以通过皮肤黏膜、呼吸道等部位引起感染,感染可局限也可播散。播散性镰刀菌病几乎仅发生于免疫受损患者。急性髓性白血病较之急性淋巴细胞白血病更易发生镰刀菌感染。镰刀菌病的诊断主要根据宿主因素、临床表现（75%的镰刀菌病会有皮肤表现）、真菌培养、组织病理学检查。分子生物学技术的应用可以将形态学难以区分的镰刀菌鉴定到种。镰刀菌病很难治疗,尤其是播散性镰刀菌病的病死率很高。体外药敏试验结果表明氟康唑、伊曲康唑、氟胞嘧啶对镰刀菌无抗菌活性,目前主要治疗方法是联合应用伏立康唑和两性霉素B,尤其是单独应用抗真菌药无效的病例。     

以皮肤受累为首发表现的播散性念珠菌病1例并文献复习

目的：播散性念珠菌病是一种致命性真菌感染性疾病,在免疫缺陷患者中发病率逐年增多,报道1例以双下肢多发皮下结节为首发表现,伴有肺及脑受累的播散性念珠菌病,并文献复习播散性念珠菌病的皮肤受累临床表现。方法患者女,37岁。因双下肢多发皮下结节6个月余就诊。有局灶节段性肾小球硬化病史,口服强的松及他克莫司2a余。取患者皮损组织行病理学检查,皮损组织、脓液、血、痰、尿、粪、脑脊液进行真菌镜检及真菌培养,并文献检索统计播散性念珠菌病皮肤受累患者临床特点。结果皮损组织病理见假菌丝,皮损组织、脓液、痰、尿、粪标本直接涂片均见假菌丝并培养出白念珠菌,CT显示肺受累,诊断为播散性念珠菌病,予抗真菌治疗,患者皮损愈合及肺部病灶部分吸收,但因自行停药,最终出现颅内播散。结论以皮损为首发表现的播散性念珠菌病临床罕见,临床诊疗中应重视应用免疫抑制剂患者皮损的组织病理及微生物检查,及早进行诊断和治疗,防止出现系统性播散,从而降低死亡率。     

1例皮肤播散型孢子丝菌病的分离菌株的基因鉴定

孢子丝菌病是由申克孢子丝菌及其卢里变种感染引起的皮肤、皮下组织和附近淋巴系统的亚急性和慢性感染,偶可播散至全身引起多系统损害。该病遍布全世界,我国孢子丝菌病主要是由申克孢子丝菌引起。孢子丝菌一般生存在土壤和植物上,人的皮肤接触带菌植物或土壤后可引起感染。临床上主要表现为固定型和淋巴管型孢子丝菌病,皮肤播散型孢子丝菌病少见。现认为机体感染申克孢子丝菌引起的不同的临床型别与机体免疫状态、申克孢子丝菌的致病力及其基因差异相关[1-2]。我     

侵袭性毛孢子菌感染的诊断和治疗

侵袭性毛孢子菌感染主要包括真菌血症、单个器官感染和播散性毛孢子菌病,常发生于免疫低下人群,尤其因患有血液病或化疗而出现中性粒细胞减少的患者,诊断需结合临床表现、组织病理活检和血培养等。由于毛孢子菌属种间鉴定的困难和标准化体外药敏试验的缺乏,毛孢子菌病的最佳治疗方案尚未确定,应根据体外药敏试验制定个体化治疗方案。     

骨髓中检出组织胞浆菌1例

组织胞浆菌（Histoplasma capsulatum）是一种深部真菌,可引起人体深部组织胞浆菌病。最近我们从1例患者骨髓涂片瑞氏染色、PAS染色、骨髓病理活检中检出组织胞浆菌,现予报道。     

镰刀菌所致皮肤感染的文献回顾

镰刀菌主要为植物致病菌,但也可引起严重人类感染。镰刀菌病临床表现形式多样,本文主要综述相关的皮肤感染,分为局限性皮肤感染及播散性感染,诊断多较困难。由于该属真菌对抗真菌药物存在天然耐药,播散性镰刀菌病死亡率可达80%-90%。本文对Medline和中文文献数据库中的相关文献进行了系统查阅和分析,综合归纳了镰刀菌所致皮肤感染的致病种、地域分布、危险因子、临床表现形式、药物敏感性及其诊疗方案等,该综述对全面了解镰刀菌病的特征及对临床医师对本病的诊断具有重要的意义。     

一种基于环介导等温扩增技术原理的组织胞浆菌分子诊断技术

目的研发一种基于环介导等温扩增(1oop-mediated isothermal amplification,LAMP)技术原理的组织胞浆菌感染的分子诊断技术。方法以组织胞浆菌为研究对象,针对其种特异性的M抗原基因序列,设计并筛选数套基于LAMP技术的特异性引物,同时优化其反应条件,建立一种针对组织胞浆菌感染的快速分子鉴定技术。结果该LAMP技术在65℃、90min反应条件下,对组织胞浆菌基因组DNA的检测敏感度达到5.3pg/反应(即5.3×10-12 g,约160个基因组DNA拷贝),且与其相近种属真菌无交叉反应。结论我们研发的这种基于LAMP技术原理的组织胞浆菌分子诊断技术具有操作简便、特异性及敏感性高等优点,具有临床推广应用的潜力。     

Unusual Orofacial Manifestations of Histoplasmosis in Renal Transplanted Patient

Histoplasmosis is a fungal infection caused by the Histoplasma capsulatum. Mucosal manifestations are uncommon, but, when present, they are usually associated with pulmonary or chronic disseminated infection. The course of the disease is often related to the host immune response. The purpose of this article is to describe the clinical and microscopic findings of unusual involvement of nasal cartilage and septal destruction, and oral lesions of histoplasmosis in an immunosuppressed patient who presented an unusual form of the disease.     

A case of disseminated histoplasmosis diagnosed after oral presentation in an old HIV‐negative patient in Sweden

Histoplasmosis is an endemic disease in various regions such as North America and South‐East Asia but remains rare in Europe. Disseminated histoplasmosis is unusual in HIV‐negative patients. Here, we describe a case of disseminated histoplasmosis in an HIV‐negative patient diagnosed after oral presentation.     

How I Treat Histoplasmosis

Histoplasmosis is an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Some important manifestations of infection include acute or chronic pulmonary disease, histoplasmomas, progressive disseminated histoplasmosis, and central nervous system infection. Depending on the clinical presentation, site of infection and severity of disease, either amphotericin B preparations followed by itraconazole, or itraconazole alone have become the preferred treatments. Because prolonged therapy (6 weeks to 24 months) may be required, careful monitoring for nephrotoxicity in patients on amphotericin B preparations is necessary. In addition, in patients receiving itraconazole, vigilance for drug interactions and pharmacokinetic properties is warranted. Histoplasma antigen testing has improved rapidity of diagnosis and the ability of long-term monitoring for clinical response in patients with histoplasmosis.     

High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study

BackgroundHistoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions.MethodologyWe conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation.Principal findingsEvidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections.ConclusionsThe high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.     

Histoplasmosis in a Brazilian center: clinical forms and laboratory tests

Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic in many regions of the Americas, Asia and Africa. It has a wide spectrum of clinical manifestations, from asymptomatic infection to severe disseminated disease. A retrospective study was carried out to describe the clinical forms and assess the clinical significance of the laboratory diagnostic tests of patients with histoplasmosis during the period of July 1987 to December 2003 at Instituto de Pesquisa Clínica Evandro Chagas/ FIOCRUZ, RJ, Brazil. Seventy-four patients were included. Forty-nine percent of the cases (n = 36) occurred in HIV positive patients who presented with disseminated disease. The remaining 38 cases were classified in different clinical forms. Histoplasma capsulatum was isolated from 69.5% of the clinical specimens sent to culture. Immunodiffusion and immunoblot were positive in 72.6% and 100% of the performed tests, respectively. Histopathologic findings suggestive of H. capsulatum were found in 63.2% of the performed exams. Serology had a lower proportion of positivity amongst AIDS patients, when compared with HIV negative patients (X2 = 6.65; p lower than 0.008). Statistical differences between AIDS and non-AIDS patients were not observed with culture and histopathology. The specific role of each test varies according to the clinical form. Physicians need to know the value and limitations of the available diagnostic tests, but before that, they have to think about histoplasmosis and consider this clinical entity in their differential diagnosis.     

Coccidioidomycosis and other endemic mycoses in Mexico

The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.     

Histoplasmosis: Epidemiology in Latin America

Histoplasmosis is a frequent health problem in Latin American countries, but the fact that it is not a reportable disease prevents reliable estimates of its real incidence and impact on public health. Epidemiologic and clinical data remain patchy in general, and in some countries the information available is very limited. Histoplasmosis has a significant public health impact in susceptible populations such as immunosuppressed individuals, in whom the disease is associated with poor outcomes. Limited availability of diagnostic tools in many regions of Latin America is an additional problem, as many patients are already severely ill by the time of the diagnosis. Efforts are therefore necessary to ensure early diagnosis and appropriate treatment, limit the severity of the disease manifestations, and reduce morbidity and mortality. This paper reviews important aspects of the epidemiology of histoplasmosis, the most clinically significant endemic mycosis in Latin America.     

Diagnosis and management of histoplasmosis

Histoplasmosis occurs sporadically or during outbreaks in endemic areas. The risk for severe forms of histoplasmosis is substantially higher among the growing population of immunocompromised patients. Recent research efforts have focused on analyzing epidemics, identifying risk factors for the disease, developing improved noninvasive diagnostic assays, and assessing the roles of newer antifungal drugs. Guidelines have been published for the prevention of occupationally acquired histoplasmosis and for reducing the risk of disease in patients with HIV infection. A third-generation Histoplasma antigen assay has been developed, which has superior performance characteristics compared to other noninvasive diagnostic tests. Treatment guidelines for the various clinical forms of histoplasmosis have been formulated and updated. Two newer azoles with activity against Histoplasma capsulatum, voriconazole and posaconazole, have been released; in vitro susceptibility data and animal model results have been reported, and treatment experience with these drugs has accumulated.     

An unusual presentation of disseminated histoplasmosis in a non-HIV patient from Vietnam

BackgroundHistoplasmosis is a systemic infection caused by the dimorphic fungus Histoplasma capsulatum, naturally found in nitrogen-rich soil, whose main transmission route is the inhalation of conidia. Up to 95% of histoplasmosis cases are asymptomatic or transient, and the remaining 5% of cases have pathological manifestations in the lungs, bone marrow, liver, spleen, intestine, mucous membranes, and rarely on the skin. This mycosis has been reported from many endemic areas, mainly in immunosuppressed patients, such as HIV-positive patients, and its disseminated form is rarely reported.Case reportHistoplama capsulatum was isolated and identified by means of microscopy, culture characteristics and nested PCR from the cutaneous lesions of a non-HIV patient from Vietnam. The patient improved significantly with systemic itraconazole treatment.ConclusionsDisseminated histoplasmosis with cutaneous involvement in non-HIV patients is an extremely unusual presentation.