伊曲康唑治疗婴儿泛发性皮肤念珠菌病1例

采用伊曲康唑治疗1例婴儿泛发性皮肤念珠菌病。患儿男,4月大,3个月时无明显诱因臀部出现红斑、丘疹、渗出、糜烂,渐波及颈部、面部,口腔内有一灰白色膜。真菌镜检口腔内芽生孢子及假菌丝阳性,颈、臀部分泌物真菌培养白念珠菌生长。予伊曲康唑20mg[5mg/(kg·d)]口服15天,皮损好转。3个月后随访,皮肤恢复正常,未见复发。查肝功能未见异常。     

系统性白念珠菌病患者血清中芽管抗体的检测

目的 探讨一种诊断深部白念珠菌病的新方法.方法 以间接免疫荧光法测定白念珠菌系统感染患者血清中芽管抗体的滴度,并与常规真菌检测结果及菌株磷脂酶活性相比较.结果 血清中芽管抗体检测与常规检测方法(镜检+培养)阳性率比较,有较好的一致性(P<0.001).磷脂酶活性测定结果显示,感染组患者分离株较定植组的磷脂酶活力差异有统计学意义(P<0.05);磷脂酶活性与芽管抗体滴度具有相关性,P<0.001.结论 检测白念珠菌芽管抗体在系统件白念珠菌感染诊断中具有一定的诊断意义.     

慢性皮肤黏膜念珠菌病

报告1例白念珠菌引起的皮肤黏膜念珠菌病，患儿女，7岁，全身散在丘疹5年，加重伴指疣状增生1年，同时出现口腔黏膜，皮肤及甲板损害，双手掌疣状赘生物，手指末节残缺，变形。口腔黏膜白斑，北部皮损组织及粪便真菌培养均为白念珠菌生长。皮肤组织病理改变为表皮角化明显，角质层中查见大量真菌菌丝。经伊曲康唑，制霉菌素等药治疗后，皮损逐渐好转。     

慢性皮肤黏膜念珠菌病1例及实验室研究

报道1例慢性皮肤黏膜念珠菌病患儿,并对其致病菌进行实验室研究.对患儿的临床情况进行分析总结,对致病菌进行分离培养、形态学鉴定、药敏试验、基因鉴定和RAPD基因型分析.患儿男,3岁,口腔、面部、双上肢慢性皮肤黏膜念珠菌病,使用伊曲康唑治疗3个月痊愈.致病菌经形态学和ITS区测序均鉴定为白念珠菌,药敏实验显示该菌对5-氟胞嘧啶、伊曲康唑、制霉菌素敏感,对特比萘芬中度敏感.经基因型分析,患儿不同部位皮损均由同一白念珠菌感染所致.本例患儿为白念珠菌引起的慢性皮肤黏膜念珠菌病,伊曲康唑等药物治疗有效.白念珠菌感染仍是引起皮肤黏膜念珠菌病的主要原因.     

阴道分离的念珠菌体外抗真菌药物敏感性分析

目的 探讨念珠菌在女性阴道黏膜所致的不同表现与其对抗真菌药物敏感性之间的关系。方法 应用NCCLSM27-A方案推荐的微量液体稀释法,测定对来自外阴阴道念珠菌健康携带者、外阴阴道念珠菌病和复发性外阴阴道念珠菌病的念珠菌对抗真菌药物的敏感性。结果 8种抗真菌药对光滑念珠菌和克柔念珠菌的MIC值几乎均比白念珠菌高。来自复发性外阴阴道念珠菌病患者的菌株MIC值较高,而健康带菌者菌株的MIC值较低。耐药菌株主要来源于复发组,健康带菌者来源的白念珠菌菌株对伊曲康唑、氟康唑、酮康唑和制霉菌素未见有耐药菌株出现。结论 外阴阴道念珠菌病治疗中应重视非白念珠菌的耐药性,长期或间断应用抗真菌药物治疗,可能诱导耐药株的产生。     

牛痘样水疱病样皮肤淋巴瘤与慢性活动性EB病毒感染的关系

目的 报道6例牛痘样水疱病样皮肤淋巴瘤,并研究其与慢性活动性EB病毒感染的关系.方法 临床病理分析、皮损免疫组织化学染色、血清学分析、EB病毒编码RNA原位杂交、外周血EB病毒DNA测定.结果 6例患者皮损均为反复发作的丘疹、丘疱疹、坏死、痘疮样瘢痕,其中4例还伴有程度不同的颜面、手足水肿.所有患儿均有长期间断发热等症状.皮损病理可见表皮多房性水疱,真皮全层大量淋巴细胞浸润,细胞形态异形,可见病理分裂象.4例皮损病理免疫组化染色,可见大量CD56阳性细胞,散在的CD3和CD45RO阳性细胞,T细胞内抗原-1和粒酶B染色阳性,诊断为牛痘样水疱病样皮肤NK/T细胞淋巴瘤;2例组化染色CD3和CD45RO阳性,CD56阴性,诊断为牛痘样水疱病样皮肤T细胞淋巴瘤.6例皮损均可见EB病毒编码RNA原位杂交阳性肿瘤细胞,血清学检查EB病毒衣壳抗原IgG抗体滴度升高,其中2例滴度为1:5120,2例为1:2560,2例为1:1280;2例患者外周血EB病毒DNA拷贝数高于正常.6例患儿均证实患有慢性活动性EB病毒感染.结论 牛痘样水疱病样皮肤淋巴瘤主要表现为颜面手足肿胀、水疱、痘疮样瘢痕,病理表现主要为真皮异形淋巴细胞浸润和血管中心坏死,免疫表型以NK/T型多见.慢性活动性EB病毒感染与该型淋巴瘤发病密切相关.     

结缔组织病患者念珠菌深部定植的危险因素分析

目的 了解结缔组织病患者念珠菌深部定植的发生率及相关危险因素.方法 对153例结缔组织病患者和63例健康人的咽拭、中段尿、肛拭标本进行真菌培养,采用Logistic相关回归分析模型,对患者念珠菌深部定植的危险因素进行相关性分析.结果 患者组的念珠菌深部定植率35.29%显著高于健康人组7.94%,菌种分析以白念珠菌最常见.患者组血红细胞计数降低,尿蛋白增多,血清补体(CH50、C3、C4)水平降低,糖皮质激素使用每日均量较高以及广谱抗生素使用与结缔组织病患者念珠菌深部定植有显著相关性;而性别、年龄、身高、体质量、病程、有结缔组织病家族史、既往脏器损害、血白细胞及中性粒细胞计数低下、血小板计数低下、尿红细胞与白细胞异常增多、糖皮质激素使用总量与疗程、某些免疫抑制剂(环磷酰胺、硫唑嘌呤等)的使用、雷公藤的使用总量与疗程、窄谱抗生素的使用等与结缔组织病患者念珠菌深部定植无显著相关性.结论 结缔组织病患者念珠菌深部定植率显著高于健康人,控制相关危险因素将减少念珠菌深部定植的发生.     

厚壁孢子根毛霉引起深部真菌病一例

目的 报道厚壁孢子根毛霉引起深部真菌病1例.方法 了解患者的病情经过,病理检查及相关实验室检查,并作病变组织真菌镜检、培养与鉴定.结果 患者男,41岁.临床表现为右臀部、两侧腹股沟及胰头后方先后出现肿块,伴轻度疼痛,进行性加重.后期皮肤肿块处出现溃疡、坏死、黑痂,伴恶心、呕吐、肝功能异常.病理表现为真皮及皮下组织慢性肉芽肿改变,于血管内或多核巨细胞内、或组织间见分支不分隔或少数分隔的粗大菌丝,并可见少数厚壁孢子及分隔菌丝,PAS染色阳性.真菌鉴定为厚壁孢子根毛霉(Rhizomucor chlamydosporus).结论 该病例初表现为侵袭性肉芽肿,后出现坏死性溃疡,进展较快,最后导致恶液质而死亡.     

厚皮马拉色菌引起面部疣状增生性结节一例

目的 报道1例由厚皮马拉色菌引起的面部疣状增生性结节。方法 采用真菌直接镜检与培养、温度试验、过氧化氢酶试验、皮肤病理检查、PAS染色和扫描电镜对1例面部疣状增生性结节女性患者分离出的菌株进行鉴定。结果 皮损病理检查显示真皮内慢性炎症细胞弥漫性浸润,PAS染色见真皮内散在的孢子。皮损和宠物狗皮屑革兰氏染色,镜检发现大量革兰氏阳性酵母样孢子及芽孢。含橄榄油及不含油SDA 27℃培养2周,见乳白色酵母样菌落生长。该菌在含油SDA培养,27℃生长最佳;过氧化氢酶试验阴性。扫描电镜观察显示菌体较小,芽颈较宽,基围较厚,孢子呈球形、卵圆形、椭圆形等形态。上述结果提示该菌为厚皮马拉色菌。结论 厚皮马拉色菌引起面部疣状增生性结节为国内首例报道,氟康唑联合局部冷冻治疗获得良好疗效。     

HIV/AIDS患者口咽部念珠菌病与CD4+、CD8+T淋巴细胞分析

目的 研究HIV/AIDS患者的口咽部念珠菌病的发病特点,CD4⁺计数、CD8⁺计数、CD4⁺/CD8⁺比值的分布特点,以及抗真菌治疗的特点。方法 观察20例合并口咽部念珠菌病的HIV/AIDS患者和对照组口腔病损情况,病损部行真菌镜检和真菌培养,外周血流式细胞仪检测CD4⁺、CD8⁺计数。研究组和对照组伊曲康唑治疗第1周、第2周、疗程结束时、停药后两周真菌学疗效比较。结果 19例为白念珠菌感染,1例为近平滑念珠菌感染。20例艾滋病患者可见舌部感染6例,口腔侧壁感染14例。CD4⁺、CD8⁺计数和CD4⁺/CD8⁺比值分别在119.40±127.43、652.50±338.57和0.163±0.130范围。伊曲康唑治疗HIV/AIDS组第1周、第2周、疗程结束时、停药后两周真菌清除率分别为16.67%、50.00%、61.11%、66.67%。结论 HIV/AIDS患者口咽部念珠菌感染的最常见致病菌是白念珠菌,最常见靶部位是舌和口腔侧壁。HIV/AIDS患者的口咽部念珠菌病抗真菌疗效与免疫状态有关。     

Altered,but not diminished specific T cell response in chronic mucocutaneous candidiasis patients

Patients suffering from chronic mucocutaneous infections with the yeast Candida albicans (CMC) are discussed to have an underlying primary cellular immunodeficiency. In order to characterise cellular immunity in CMC patients, we analysed chemotaxis and myeloperoxidase (MPO) releases of neutrophils and T cell proliferation and cytokine production to Candida albicans. Patients with chronic mucocutaneous candidiasis (n = 4) and healthy volunteers of same sex and similar age (n = 14) were enrolled into the study. Neutrophil chemotaxis was assessed by transwell migration assay, and MPO release by ELISA. T cell proliferation capacity was investigated by thymidine incorporation and cytokine secretion in supernatants by ELISA. Neither neutrophil migration nor MPO release differed between CMC patients and healthy controls. The relative lymphocyte stimulation index (SI Candida/SI PHA) was heterogenous, but overall it was higher in CMC patients compared to controls. However, Candida-specific IFN-γ production was significantly reduced in CMC patients. Notably, Candida-specific T cell IL-10 production was markedly higher in CMC patients. The inability to clear the yeast Candida albicans in our CMC patients does not seem to be due to an impaired neutrophil function or reduced antigen specific proliferation of lymphocytes. In fact, our patients tended to proliferate stronger to Candida antigen relative to PHA than healthy controls. However, the impaired Th1 cytokine production with an enhanced IL-10 production could play an important role in the pathogenesis of chronic mucocutaneous Candida infections.     

Immunological studies in chronic mucocutaneous candidiasis before and after ketoconazole treatment

Immune functions were studied in eight patients with chronic mucocutaneous candidiasis representing a broad clinical spectrum of this disease. Clinical improvement after ketoconazole for 6 months was not associated with amelioration of cutaneous delayed hypersensitivity to Candida antigen or the in vitro lymphocyte responses to Candida antigen of T-cell mitogens.     

气相色谱诊断播散性念珠菌病的研究

本文报告用气相色谱法检测血清甘露糖醋酸醛糖腈乙酯衍生物诊断深部念珠菌病.实验显示播散性念珠菌病血清甘露糖浓度最高,平均为925.24±73.64μg/ml.系统性(非播散性)病例较低,平均为654.58±31,19μg/ml.而健康人最低,平均502.76±76.83μg/ml.3者有显著差异(P<0.01).兔感染白念珠菌一天后血清甘露糖浓度迅速增高(267.36-1053.57μg/ml).而新型隐球菌、烟曲霉、裴氏着色霉菌及几种常见细菌培养标本均未检测到甘露糖.此法对诊断系统性和播散性念珠菌病有实用价值,特别对后者的早期感染提供了有效方法.     

A case of candidal umbilical granuloma

A case is reported of a 14-year-old boy with a mass arising from the umbilicus, which was a large, well-organized candidal granuloma. Cell markers showed normal numbers and distribution of peripheral T and B lymphocytes but there was no reaction to intradermal injection of Candida, suggesting a specific T-cell defect such as occurs in chronic mucocutaneous candidiasis.     

Ketoconazole treatment of 13 patients with chronic mucocutaneous candidiasis. A prospective 3-year trial

Long-term results of initial ketoconazole treatment were evaluated in 13 patients with chronic mucocutaneous candidiasis followed up for 3 years. Six of them shared 11 endocrine or autoimmune disorders. All patients responded well to treatment but 1 dropped out owing to anxiety. Clinical and mycological clearing was achieved in 1-2 months for the mouth, 2 months for the skin, 3-4 months for paronychiae and 4-14 months for the nails. Bacterial infections persisted in 2 cases. After withdrawal of ketoconazole, 2 patients have remained in remission. Continuous therapy was required in 2 cases and the others were treated intermittently owing to recurrences of Candida stomatitis. Ketoconazole was well tolerated. An asymptomatic reversible increase of serum hepatic enzymes occurred in 1 case. Oral ketoconazole is the drug of choice for treatment of chronic mucocutaneous candidiasis but long-term observation is required.     

阴道念珠菌病患者阴道分泌物总RNA提取方法的研究

目的 探索一种简单有效的人体阴道分泌物标本总RNA提取方法并验证其可行性。方法 采用人体上皮细胞与念珠菌标准菌株的混合物（106 ∶ 106）,对匀浆、玻璃珠和液氮研磨三种破壁方法,纯化柱、酚两种提取方法组合产生的5种不同RNA提取方法进行比较。并将提取效果最好的方法应用于临床标本。结果 5种方法均可提取出总RNA,其中,热酚法提取质量浓度最高,达到0.6546 g/L,其次为RNeasy试剂盒提取方法为0.6010 g/L,玻璃珠法为0.2678 g/L,匀浆后TRIzol法为0.2284 g/L,液氮研磨后TRIzol法为0.2115 g/L。但电泳结果显示,以液氮研磨后TRIzol提取质量最好,而且标准菌株及培养细胞混合物两种细胞成分RNA均被提取,RT-PCR以及荧光定量PCR验证结果显示,该方法可以应用于临床标本RNA提取。结论 液氮研磨后TRIzol法是一种简单而有效的阴道分泌物临床标本RNA提取方法,而且提取物可以满足常规下游实验的需求。     

Familial chronic mucocutaneous candidiasis associated with autoimmune polyendocrinopathy. Treatment with fluconazole: 3 cases

BACKGROUND: Familial candidiasis endocrinopathy is a hereditary disease variably associated with i) a dysfunction of the parthyroid, adrenal, thyroid, pituitary or ovarian glands as well as the pancreas (diabetes), liver (hepatitis) and gastric wall cells (Biermer's disease); ii) chronic mucocutaneous candidiasis; iii) autoimmune manifestations: chronic keratitis, pelade, vitiligo, hemolytic anemia. CASE REPORTS: We cared for three pediatric patients with chronic mucocutaneous candidiasis associated with an autoimmune polyendocrinopathy. There was a familial context in all cases with an autosomal dominant inheritance in the first case and an autosomal recessive inheritance in the two others who were siblings. In all three cases, the chronic mucocutaneous candidiasis began before the age of 5 years and had preceded the development of the endocrinopathy. Fluconazole was effective in all three cases. DISCUSSION: Chronic mucocutaneous candidiasis may appear as the inaugural symptom of an autoimmune polyendocrinopathy and should lead to a familial study with an andocrinology work-up to determine any clinical manifestations and biological evidence of autoimmunity. Fluconazole does not have marketing approval for children, but provides good control of the fungal infection, particularly in the ungueal localization, and is well tolerated.     

Autoimmune polyendocrinopathy and chronic mucocutaneous candidiasis

The authors report the case of a child who, at the age of 18 months showed signs of hypoparathyroidism together with gastrointestinal, then buccal, then ungual candidiasis. Acute adrenal failure occurred when he was 5 1/2 years' old. At the age of 10, the patient developed alopecia areata and interstitial keratitis. Immunological investigations yielded normal results, except that serum was weakly positive for anti-adrenal antibodies at 1/10th. The mucosal and ungual candidiasis infection was cured by ketoconazole, and the various endocrine abnormalities were corrected with the appropriate replacement therapies. This case prompted the authors to review the candidiasis/"polyglandular autoimmune disease" association. Whitaker's triad consists of candidiasis, hypoparathyroidism and chronic renal failure, 2 or these 3 elements being sufficient to make the diagnosis. Numerous other associations have been described; they are presented here in table form in descending order of frequency, with candidiasis/hypoparathyroidism coming on top of the list (70 p. 100). The fairly constant chronological order in which these different pathologies appear is one of the peculiarities of the syndrome: candidiasis often precedes hypoparathyroidism and adrenal insufficiency. Alopecia areata does not seem to be frequent, but its true incidence is difficult to quantify since lesions of the scalp and/or skin appendages are poorly documented in the literature. Alopecia and keratopathy seem to be of autoimmune origin. Mucocutaneous candidiasis too is specific, the mucosae and nails being constantly involved. This type of candidiasis does not exist in other forms of hypoparathyroidism. Chronic mucocutaneous candidiasis is found in many different diseases and is due to immunodeficiency against Candida spp.(ABSTRACT TRUNCATED AT 250 WORDS)     

Necrolytic migratory erythema. Distinctive dermatosis of the glucagonoma syndrome.

Glucagon-secreting tumors of the pancreatic islets (glucagonomas) produce a distinctive syndrome in which weight loss, diabetes mellitus, anemia,and prominent mucocutaneous findings occur. The cutaneous component-necrolytic migratory erythema--may be polymorphous, but most commonly manifests as erosions and crusts of the groin, perineum, buttocks, distal part of the extremities, and central area of the face. Alternatively, scaly papules and plaques may predominate in these areas. The eruption may resemble such dermatoses as pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, and severe seborrheic dermatitis. Two patients with chronic, previously undiagnosed dermatoses had necrolytic migratory erythemia, which led to the discovery of glucagonomas present in each. In one patient surgical resection of the tumor resulted in total clearing of the rash within 48 hours. Awareness of this distinctive entity may lead to early diagnosis and, possibly, cure.     

DIFFUSE CHRONIC GRANULOMATOUS MUCOCUTANEOUS CANDIDIASIS

A 3-year-old Thai boy with diffuse chronic granulomatous mucocutaneous candidiasis, recurrent bacterial skin infection and adrenal insufficiency is reported. Candida albicans was demonstrated in the dermal granuloma. He had a defect in cell-mediated immunity and was anemic. Although therapy with topical clotrimazole, oral iron, systemic antibiotic and low-dose of prednisone gave a dramatic result, he died of disseminated cryptococcosis.