表现为皮肤溃疡和骨髓炎的播散性隐球菌病一例研究

A Case of Disseminated Cryptococcosis with Cutaneous Manifestations and Osteomyelitis: Clinical and Laboratory Investigations

目的报告一例播散性隐球菌病的临床、实验研究和治疗结果。方法和结果患者女,33岁。1年前上臂、肩、臀及大腿长结节,此间怀孕并早产。产后半个月新发结节泛发全身。3个月前诊断为“血源播散性肺结核”,但抗结核治疗无效。体检发现面部、牙龈、躯干、臀部及四肢共39个结节和溃疡,左胫、腓骨骨质破坏及窦道。脓涂片及病理活检见脓液和坏死组织内有大量真菌孢子,培养酵母样菌落生长,尿素酶及咖啡酸试验阳性。经API酵母菌反应条和血清学鉴定为新生隐球菌血清型A。将菌种接种于大小鼠后发现脑、肺、肝等易受累。临床分离株核糖体内转录间隔2区序列分析法鉴定为新生隐球菌新生变种。停抗结核药,用抗真菌药治疗。强化段用两性霉素B和氟康唑,维持段口服伊曲康唑。局部用两性霉素B。30d后结节消失,200d后溃疡和窦道全部愈合,277d时停抗真菌药,患者痊愈。

Objective To report a case of disseminated cryptococcosis with cutaneous manifestations and osteomyelitis. Methods and Results A 33 year old female was admitted due to multiple nodules and ulcers on the upper arms, shoulders, buttocks and thighs for one year. The patient was pregnant when admitted, and gave birth to a premature baby during her illness. The nodules increased half a month after delivery, which was suspected to be hematogenously disseminated pulmonary tuberculosis and was given anti tuberculous therapy for three months but failed. Physical examination showed there were 39 nodules or ulcers on the face, gum, trunk, buttocks and extre mities. The bone structure of the left tibia and fibula destroyed and a sinus developed on the left fibula. Microbiologic examination showed that lots of spores were seen in the smear of pus and necrotic tissues, which produced yeast like colonies in culture with positive urease and caffeic acid test. Cryptococcus neoformans, serotype A was identified by API yeast reaction band and serology. Inoculation with mice and rats showed that their brains, lungs and livers were involved easily. Further identification as C.neoformans var.neoformans was obtained based on sequence analysis of ribosomal internal transcribed spacer region 2. The anti tuberculous therapy was stopped and anti fungal therapy was initiated at once. Intravenous and topical amphotericin B in combination with fluconazole were chosen in the initial therapy and itraconazole for maintenance. The nodules disappeared after 30 days and the last ulcer in the left tibia healed completely after 200 days. The anti fungal therapy was discontinued after 277 days and the patient was completely cured.