Ophthalmic manifestations of Cryptococcus gattii species complex: a case series and review of the literature

AIM:To report 4 cases of Cryptococcus gattii(C.gattii)species complex infection with diverse ophthalmic manifestations,and to review the literature to examine pathobiology of disease,classical ophthalmic presentations and outcomes,and treatment modalities for this emerging pathogen.METHODS:Cases of C.gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series.Additionally,a MEDLINE literature review was conducted to identify all reported cases of C.gattii with ophthalmic manifestations from 1990-2020.Cases were reviewed and tabulated,together with our series of patients,in this report.RESULTS:Four cases of C.gattii with ophthalmic manifestations are presented;three from Australia and one from the USA.A literature review identified a total of 331 cases of C.gattii with visual sequelae.The majority of cases occurred in immunocompetent individuals.Blurred vision and diplopia were the most common presenting symptoms,with papilloedema the most common sign,reported in 10%-50%of cases.Visual loss was reported in 10%-53%of cases,as compared to rates of visual loss of 1%-9%in C.neoformans infection.Elevated intracranial pressure,cerebrospinal fluid(CSF)fungal burden,and abnormal neurological exam at presentation correlated with poor visual outcomes.The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures.CSF diversion procedures should be considered for refractory cases.Acetazolamide and mannitol are associated with high complication rates,and adjuvant corticosteroids have demonstrated higher mortality rates;these treatments should be avoided.CONCLUSION:Permanent visual loss represents a devastating yet potentially preventable sequelae of C.gattii infection.Intracranial hypertension needs to be recognised early and aggressively managed.Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended.     

肾移植患者播散性隐球菌病致广泛皮下结节1例

患者女性34岁，行肾移植术后6年，一直使用免疫抑制剂治疗。不明原因发热7天入院。体检：体温38℃，患者背部皮肤广泛3cm至6cm大小不等皮下结节，表面皮肤未见破损，呈红色、偏硬、有压痛。皮肤组织活检见深达赵皮层急性肉芽肿性炎，炎症组织中弥漫酵母样细胞。经培养鉴定并查血、脑脊液培养鉴定均可见新生隐球菌生长，诊断为播散性隐球菌病。予氟康唑200mg每日静脉滴注治疗。患者体温消退，皮疹也逐步消退。     

Cryptococcal cellulitis in a renal transplant patient.

A 54-year-old male patient was admitted due to fever and cellulitisof the left leg (Figure 1). Three years before, he had undergonerenal transplantation, and his immunosuppressive regimen was     

Examination of a Chinese-made cryptococcal glucuronoxylomannan antigen test in serum and bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients

BackgroundWe presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population.MethodsBetween February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples.ResultsHere, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p < 0.001) with pulmonary lesion size, while the BALF value showed no correlation (r: 0.253, p: 0.13). The positivity rate of BALF was higher than that of serum when the diameter of the pulmonary lesion was small (diameter less than 20 mm). Moreover, the serum cryptococcal GXM antigen levels showed an overall decreasing trend with the decrease in pulmonary lesion size after antifungal therapy in patient follow-up.ConclusionsThe Chinese-made cryptococcal GXM antigen test has better sensitivity and specificity for diagnosing pulmonary cryptococcosis in the HIV-negative Chinese population, and it could be used to diagnose and to monitor this disease.     

肺隐球菌病35例临床分析

目的探讨肺隐球菌病的临床特点,提高医务人员对肺隐球菌病的临床诊疗能力。方法回顾性分析东莞市人民医院35例确诊为肺隐球菌病患者的临床症状、胸部影像和治疗情况。结果 35例肺隐球菌患者中,19例(54.3%)无明显基础疾病;29例(82.9%)的临床症状主要表现为咳嗽、咳痰等;影像学表现为肺单发或多发结节肿块影(11例,31.4%),或渗出实变影(12例,34.3%),或两种病灶混合存在(12例,34.3%);19例患者红细胞沉降率升高;13例患者白细胞轻度增高;2例患者无法判断疗效,其余病情均有好转。结论肺隐球菌病的临床症状与影像学表现无特征性,确诊需依靠病理活检,经皮肺穿刺活检是有效的诊断手段。     

胶体金免疫层析法检测CrAg对非HIV感染肺隐球菌病患者疗效的评估价值

目的 探究非人类免疫缺陷病毒（HIV）感染肺隐球菌病患者临床特点及胶体金免疫层析法（LFA）检测隐球菌荚膜多糖抗原（CrAg）对其疗效的评估价值。方法 选取2019年1月—2020年12月在重庆医科大学附属永川医院就诊的114例非HIV感染肺隐球菌病患者。所有患者行CrAg-LFA检测,以组织病理检查结果为金标准,记录患者治疗后不同时间点（1个月、3个月、6个月、1年）的CrAg滴度和疗效,比较不同CrAg-LFA检测结果患者的临床资料及不同CrAg滴度患者的疗效。结果 不同性别、年龄、C反应蛋白、白细胞计数患者的CrAg阳性率比较,差异无统计学意义（P >0.05）;不同临床症状患者的CrAg阳性率比较,差异有统计学意义（P <0.05）。不同胸部CT表现、病灶分布、累及肺叶、病变范围患者的CrAg阳性率比较,差异无统计学意义（P >0.05）。LFA的敏感性为95%（95% CI：0.818,0.991）,特异性为100%（95% CI：0.939,1.000）,阳性预测值为100%（95% CI：0.886,1.000）,阴性预测值为97.37%（95% CI：0.900,0.995）。随着治疗时间推移,CrAg的滴度呈下降趋势（P <0.05）。CrAg阳性患者不同时间点的疗效比较,差异有统计学意义（P <0.05）,11例患者治疗过程中CrAg检测逐渐转阴,其余患者治愈或好转。治疗1年后,CrAg低滴度患者疗效好于高滴度患者（P <0.05）。结论 非HIV感染肺隐球菌病患者影像学表征缺乏特异性,CrAg-LFA检测可有效评估非HIV感染肺隐球菌病患者疗效及预后,具有较好的临床指导意义。     

肺隐球菌病的临床分析

目的了解肺隐球菌病的发病特点。方法报告1例肺隐球菌病患者的临床资料,复习了74篇相关文献,总结其临床表现、影像学特点、诊断方法及治疗手段。结果肺隐球菌病的临床表现无特异,诊断依赖病理学,易并发隐球菌性脑膜炎。治疗包括抗真菌药物治疗和手术切除。结论提高对该病的认识可提高确诊率。抗真菌药物治疗,尤其术前术后应用,可减少隐球菌的播散和隐球菌性脑膜炎的发生。     

Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host

Understanding the uses and limitations of methods for rapid diagnosis of fungal disease is essential in order to diagnose and treat these infections early in their course. Antigen detection methods are useful for diagnosis of aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and penicilliosis marneffei. The accuracy of the beta-glucan assay for diagnosis of aspergillosis and candidiasis and its role in fungal diagnosis remains unclear, in part because the few published studies report widely varying specificity. Serologic tests for antibodies are also useful for diagnosis of histoplasmosis and coccidioidomycosis, but their sensitivity may be reduced by immunosuppression. While molecular diagnostic methods have been described and are available at some reference and university laboratories, their role in patient care remains uncertain, largely because of the lack of well-characterized assays and studies establishing their accuracy. Culture methods, although essential for establishing the diagnosis in some cases, have limitations for rapid diagnosis, namely insensitivity, need for invasive procedures, and delayed growth.     

Fungal panniculitis in renal transplant recipients

Abstract: Panniculitis may result due to various etiologies. In post-transplant immunosuppressed patients infection is the foremost cause of panniculitis. We present 2 cases of fungal panniculitis in renal transplant recipients. The first patient presented with non-tender firm erythematous plaques on the left thigh. Biopsy showed panniculitis with cryptococci. Subsequent investigations revealed the presence of cryptococcal antigens in the blood, urine, and bronchoalveolar lavage fluid. There was no evidence of cryptococcal meningitis. The second patient complained of subcutaneous nodules on the trunk and right thigh. Biopsy of one of the nodules showed panniculitis with histoplasma. This patient had been treated earlier (inadequately) for disseminated histoplasmosis. Both the cases responded well to conventional amphotericin B therapy. Their renal functions remained stable.