非免疫缺陷患者肺隐球菌病的临床特征及疗效分析

目的 分析非免疫缺陷患者肺隐球菌病的临床特征及疗效.方法 回顾性分析陆军特色医学中心2017年1月至2020年6月确诊肺隐球菌病患者的病历资料39例,人口学资料,基础疾病,临床表现,影像学特征,病理检查结果,治疗方案和临床结局.收集患者肺组织病理学检测结果和痰液样本,分析是否存在隐球菌感染,对部分患者进行了隐球菌抗原检...     

Clinical studies of sixteen cases with pulmonary cryptococcosis mainly with respect to serum level of cryptococcal antigen

Clinical studies of sixteen cases with pulmonary cryptococcosis, during the past six years between 1998 and 2004, were peformed mainly with respect to serum cryptococcal antigen titer. Serum cryptococcal antigen was positive in twelve of 16 cases, the other three cases were diagnosed by VATS, the other one by positive culture of cryptococcus in BALF. In these twelve cases, the serum cryptococcal antigen titer was continuously tested after treatment. The serum cryptococcal antigen titer decreased from half to 6 months after treatment. And the cryptococcal Ag changed to negative in six of the 12 cases by antifungal agents from 5 to 19 months. But four cases whose pneumonia was severe tended to have a high titer level of cryptococcal antigen and were positive for a long period. In the Chest CT of four pulmonary cryptococcosis case with negative cryptococcal antigen, all of the maximum nodule size was less than or equal to 15mm in diameter.     

艾滋病合并肺隐球菌感染的影像学诊断与鉴别诊断

肺隐球菌感染是艾滋病患者重要的机会性感染,也是其重要的死因之一,早期诊断与治疗是改善预后的重要因素,影像学作为无创性检查,在隐球菌感染的早期诊断与鉴别诊断中具有重要意义。对于非艾滋病患者合并隐球菌感染的影像学改变已经有了普遍认识,但是关于艾滋病患者相关的隐球菌影像学特征,文献报道较少,至今未有特征性的影像学表现得到影像学医生的公认。笔者通过文献复习,结合我们确诊的艾滋病相关隐球菌肺部感染病例的回顾性分析,发现还是有一定特征性改变,其中单发结节合并中心空洞是最常见的征象。掌握这些特征对艾滋病合并隐球菌感染的早期诊断有很大帮助。     

Histopathology of cryptococcosis and other fungal infections in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To gain insight into the histopathologic characteristics of fungal infection in acquired immunodeficiency syndrome (AIDS). METHODS: A review was conducted of the histopathology for 162 patients with evident fungal infection. RESULTS: The microscopic appearance of esophageal candidiasis that was common in patients with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida infection. Eighteen patients had generalized cryptococcosis, representing the commonest generalized fungal disease. The essential histologic features of the disease consisted of yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from the manifestations of both Candida and Aspergillus infections. The two histologic patterns recognized in the pulmonary cryptococcal lesions could be graded with respect to the degree and type of inflammatory reaction. The milder one consisted of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which might be simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in all 18 patients.     

A case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis]

A 54-year-old woman with a 21-year history of sarcoidosis was admitted to our hospital with dyspnea on exertion, weight loss, and the appearance of consolidation in chest radiographs. The serum level of soluble IL-2 receptor was high, and CT findings demonstrated mediastinal, hilar and abdominal lymphadenopathy. The histological findings of subpleural consolidation in a transbronchial lung biopsy of the left lung showed giant cells; and those of a CT-assisted biopsy of a retroperitoneal lymph node revealed non-caseous epithelioid cell granulomas. After the biopsy, severe thrombocytopenia (6,000/microliter) developed. With prednisolone treatment, the platelet count rose to normal and the subpleural consolidation on chest radiography was improved. Five weeks later, the had a productive cough with fever, rapidly progressive cavitary lesions and consolidation on chest radiography. Aspergillus fumigatus was detected in the sputum by PCR, and Aspergillus antigen was detected in the serum. She died of progressive respiratory failure, in spite of therapy with amphotericin B and itraconazole. We report a rare case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis.     

Autopsy case of pulmonary aspergillosis soon after convalescence from pulmonary tuberculosis

A 70-year-old man with liver cirrhosis and previous gastrectomy admitted for fever, coughing, and bloody sputum soon after convalescing from pulmonary tuberculosis had a peripheral white blood cell count of 9,900/microL, C-reactive protein of 14.1mg/dL, serum albumin of 2.0g/dL, and serum positive for antiaspergillus and beta-D glucan antibodies. Chest radiography showed thickening of the walls of the large residual cavities with previous tuberculosis lesions and infiltrates around them. On day 2 of hospitalization, Aspergillus fumigatus without other bacillus was detected in sputum culture taken on admission. Despite immediate treatment with intravenous micafungin and oral itraconazole and improved brief initial improvement, his general condition abruptly deteriorated into frequent massive hemoptysis and he developed of shock, respiratory failure, and severe malnutrition, dying 30 days later. Autopsy findings showed pulmonary aspergillosis in and around the large cavities and on the other side of the lungs. Pulmonary aspergillosis without hematological malignanciy and immunosuppression can thus be abruptly severe and fatal due to malnourishment stemming from pre-existing conditions such as chronic hepatitis despite prompt, ordinarily adequate medical treatment.     

Voriconazole as an effective therapy against pulmonary aspergillosis in a man with immunodeficiency virus-infection: a case report

A 45-year-old homosexual man with pneumocystis pneumonia and esophageal candidiasis tested positive in ELISA and Western blot analysis for HIV-1. His CD4+ T cell count was 43/microL and his HIV-RNA load was 250,000 copies/mL. He was treated with Trimetoprim-Sulfamethoxazole, Prednisolone and Fluconazole. Valganciclovir was added to treat CMV retinitis. During the clinical course, 21 days after admission, the patient presented with a temperature of 39 degrees C and blood analysis showed neutropenia. Cefepime and G-CSF were initiated, but new consolidation was observed in the upper left lobe in chest radiography. He underwent bronchoscopy and lavage culture was positive for Aspergillus fumigatus. Serum testing of galactomannan was also positive and pulmonary aspergillosis was diagnosed. The patient was initially treated with Micafungin but switched to Voriconazole when clinical symptoms worsened. An eventual clinical response was observed and pulmonary aspergillosis was controlled. Unfortunately, he died of sepsis due to MRSA 2 months later. Pulmonary aspergillosis is a devastating complication with poor prognosis in patients with HIV infection. Amphotericin-B has been the mainstay of pulmonary aspergillosis treatment, but reports indicate mortality exceeding 80%. Use of Voriconazole, a relatively new antifungal agent, may lower mortality with fewer adverse effects than conventional antifungal therapy.     

Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome

Cryptococcosis is a common opportunistic infection in patients with AIDS. Meningitis is the most frequent manifestation of infection with Cryptococcus neoformans; pneumonia due to this organism, though less frequently recognized, is also a significant entity. A retrospective review was performed of all patients seen at Duke University Medical Center between January 1981 and July 1989 who were infected with both human immunodeficiency virus type 1 and C. neoformans. Of 31 patients with these concomitant infections, 12 had cryptococcal pneumonia (10 definite and two presumptive cases). Eleven of these 12 patients had evidence of extrapulmonary cryptococcal disease as well. Chest radiography showed interstitial infiltrates in 11 instances. For ten of the 12 patients, pulmonary cultures were positive for C. neoformans. Bronchoalveolar lavage fluid from all five patients who underwent bronchoscopy yielded the organism. Acute-phase mortality from cryptococcosis was 42% among patients with pneumonia. Cryptococcal pneumonia in patients with AIDS is probably more common than has previously been recognized and typically presents as interstitial disease that may mimic other opportunistic infections.     

Effect of fluconazole on Aspergillus infection associated with chronic granulomatous disease]

Aspergillus infection is the most frequent fungal infection associated with chronic granulomatous disease (CGD), and often results in a life-threatening situation. This report describes the use of high-dose fluconazole, a new antifungal agent, for invasive Aspergillus infection in a patient with CGD. A 27-month-old boy was sent to our hospital because of unknown fever in October, 1988. He was then admitted for pneumonia and pleural effusion of the right lung in February, 1989. Treatment with antibiotics was ineffective, and cultures of throat and pleural fluid were negative. In May, 1989, Aspergillus fumigatus was cultured from a subcutaneous abscess at the point of pleural puncture. Therefore we speculated that Aspergillus might have been the cause of pneumonia. The patient was diagnosed as having CGD by NBT test. Treatment with miconazole, flucitocin and amphotericin-B syrup was ineffective. From July, 1989, he was given 100 mg/day fluconazole d.i.v., but the drug did not reach an effective serum concentration to combat Aspergillus. However, an effective concentration of fluconazole was reached at a dose of 250 mg/day, and the chest X-ray findings subsequently improved, despite occasional high fever and continued high CRP. In July, 1990, the route of fluconazole administration was changed from d.i.v. to p.o. at the same dose, resulting in a serum concentration of fluconazole higher than that achieved with d.i.v. treatment. Both the clinical and laboratory findings showed improvement thereafter. Therapy for Aspergillus infection associated with CGD was found to necessitate high doses of anti-fungal drugs over a long period, although treatment with previously employed anti-fungal drugs could not be continued due to their adverse side effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary cryptococcosis combined with pulmonary tuberculosis]

We report a rare combination of pulmonary cryptococcosis and pulmonary tuberculosis in a diabetic patient. A 63-year-old man was admitted to our hospital in January 2002 for evaluation of an abnormal chest radiograph. In 1999, the abnormality had first been detected by mass screening radiography. In 2000, an abnormality in a chest radiograph was again detected in a mass screening, and he visited another hospital. A chest CT scan revealed a cavitating lesion and several nodules in the left lower lobe. Fiberoptic bronchoscopy was performed, but was not diagnostic. The patient was referred to our hospital. He had a history of diabetes mellitus starting in 1984. The chest CT scan revealed solid nodules in the left lower lobe and several micronodules in both upper lobes. Video-assisted thoracoscopic surgery was performed and specimens were obtained from the left S8 and left S1 + 2. Histologically, cryptococci were detected in the resected left S8. In addition, mycobacterium tuberculosis was cultured from the resected left S1 + 2. A diagnosis of combined pulmonary cryptococcal and tuberculous infections was made and treatment with itraconazole, isoniazid sodium methansulfonate, rifampicin, and ethambutol hydrochloride was given.     

Usefulness of tumor marker CA-125 serum levels for the follow-up of therapeutic responses in tuberculosis patients with and without serositis

The aim of this study was to determine the usefulness of cancer antigen 125 (CA-125) serum levels in patients with tuberculosis (TB) with and without tuberculous serositis. A total of 64 TB patients with a mean age of 58.17 ± 19.05 years were enrolled in this observational case series study. All patients underwent blood sampling for the measurement of CA-125 serum levels before treatment. If the CA-125 serum levels were found to be elevated, the patients underwent blood sampling in the initial treatment phase, continuation treatment phase, and every 6 months thereafter for 2 years. The treatment outcomes of the pulmonary TB group were evaluated using chest radiography and sputum examinations, and those of the tuberculous serositis group were evaluated on the basis of the amounts of fluid determined by ultrasound. All patients in the tuberculous serositis group and 45% of the patients in the pulmonary TB group had elevated CA-125 serum levels before treatment. The pretreatment mean CA-125 serum level was significantly higher in the tuberculous serositis group than in the pulmonary TB group. CA-125 serum levels decreased along with improvement in anti-TB treatment outcomes in both the groups. In conclusion, the CA-125 serum levels in combination with clinical responses, chest radiography, and sputum examinations, can offer better monitoring of therapeutic responses in anti-TB treatment.     

Analysis of cases of central nervous system fungal infections reported in Japan between January 1979 and June 1989.

Data from 129 cases of central nervous systemic fungal infections reported in Japan between January 1979 and June 1989 were analyzed. Of 129 cases, 116 were cryptococcal meningitis, 6 candidal meningitis (including meningitis due to Trichosporon cutaneum) and 7 Aspergillus meningoencephalitis. Fifty-six of the patients with cryptococcal meningitis had an underlying systemic disease or condition. The overall survival rate was 72.4%, which was a markedly improved rate compared to earlier reports. Cryptococcal meningitis was treated most often with the combination of intravenous amphotericin B and 5-fluorocytosine and was associated with a survival rate of 81.8%. All 7 patients treated with fluconazole alone survived. Candidal meningitis occurred secondary to a shunt infection; some patients with candidemia did well when adequate therapy was instituted. Aspergillus meningoencephalitis is most often diagnosed at autopsy or in surgical specimens and the prognosis of Aspergillus meningoencephalitis is generally poor.     

Cryptococcal pneumonia in African miners at autopsy.

SETTING: Deceased miners from South Africa whose cardiorespiratory organs were submitted for autopsy for compensation for occupational lung diseases from 1996 to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in 8421 autopsied miners, a population with a high prevalence of human immunodeficiency virus (HIV) infection; 2) document the association of cryptococcal pneumonia with other pulmonary infection; 3) document the association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal meningitis; and 4) determine the accuracy of the clinical diagnosis of cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological evidence of cryptococcal pneumonia at autopsy, defined as the presence of cryptococcal organisms in the lung parenchyma, identified by staining of the mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was 7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although tuberculosis remains the most common HIV-associated respiratory disease in Africa, it is important to consider the diagnosis of cryptococcal pneumonia in acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the possibility of dual pathology.     

Immune reconstitution inflammatory syndrome producing atypical presentations of cryptococcal meningitis: case report and a review of immune reconstitution-associated cryptococcal infections

Atypical presentations of cryptococcal infection have been described as manifestations of immune reconstitution in HIV-infected patients following introduction of antiretroviral therapy. We describe a patient presenting with cryptococcal meningitis as an immune reconstitution reaction 10 weeks after initiation of anti-retroviral therapy. Subclinical CSF cryptococcal infection was demonstrated and the serum cryptococcal antigen was negative.     

A suspected case of voriconazole-induced lung injury]

A 71-year-old man was initially given a diagnosis of pulmonary nontuberculous mycobacterial infection due to Mycobacterium intracellulare (M. intracellulare). The patient was admitted because chest roentgenogram and CT scanning showed a progression of infiltrating shadows in the bilateral upper lung fields. Aspergillus fumigatus was identified by bronchial lavage. The patient was found to have chronic necrotizing pulmonary aspergillosis with M. intracellulare and treated with voriconazole (VRCZ). After fifteen days of treatment, he complained of dyspnea and cough. A chest CT showed new diffuse ground glass opacity in the left lower lobe. Arterial blood gas analysis demonstrated severe hypoxemia. Due to concerns about drug-induced lung injury, voriconazole was discontinued and corticosteroid therapy was started. VRCZ was replaced by micafungin. Thereafter, symptoms and left lower shadows resolved. Although the lymphocyte stimulation test for voriconazole was negative, we considered that this pulmonary lesion may have been an adverse reaction to voriconazole.     

A case of secondary pulmonary cryptococcosis showing various radiographic changes during its natural course without antifungal treatment]

A 58-year-old man who had been prescribed corticosteroids for rheumatoid arthritis in another hospital was admitted to our hospital for examination of an abnormal chest shadow. We obtained a positive result for cryptococcal antigen in the serum, in a measurement done as a screening test for abnormal chest shadows. We diagnosed secondary pulmonary cryptococcosis through a transbronchial biopsy. He showed various radiographic changes, including multiple nodular shadows, cavities and partial resolution during the natural course without antifungal treatment. This case taught us that secondary pulmonary cryptococcosis causes a more varied range of radiographic changes than its primary form, that measurement of cryptococcal antigen in serum is useful as a screening test of pulmonary cryptococcosis, and that it is important to consider whether a particular patient should be treated or not.     

Asymptomatic pulmonary cryptococcosis in solid organ transplantation: report of four cases and review of the literature

Abstract: Cryptococcus neoformans is the third most common cause of invasive fungal infections in solid organ transplantation. The infection generally presents as disseminated disease, involving multiple sites including the central nervous system, lungs, and skin. An increase in the incidence of primary pulmonary cryptococcal infections has been reported recently in solid organ recipients; these infections were generally symptomatic with an accelerated clinical course. We report four cases of asymptomatic pulmonary cryptococcosis in solid organ recipients (kidney, n=2, heart, n=2). In each case, an incidental finding on a routine chest radiograph led to the microbiological or histopathological diagnosis of invasive pulmonary C. neoformans infection. In these patients, cryptococcosis occurred a median of 25 months (range 7–36 months) after organ transplantation. All patients had a calcineurin inhibitor, prednisone, and azathioprine or mycophenolate mofetil as part of their immunosuppressive therapy at the time of diagnosis. Serum cryptococcal antigen was available and positive in the three patients studied; assessment of cerebrospinal fluid (CSF) of all four patients revealed no organisms by smear or culture. Therapy consisted of oral fluconazole in all cases, with flucytosine in one case, combined with resection of lung tissue in two individuals. All patients have remained free of cryptococcal disease (follow‐up median 42 months, from 18 to 88 months). Cryptococcal disease in solid organ recipients may present as asymptomatic, localized pulmonary disease. The natural history of such infections is unknown. New pulmonary radiographic findings should prompt an aggressive diagnostic evaluation including serum and CSF cryptococcal antigen assays, and a biopsy of pulmonary lesions. Prolonged therapy may be used to reduce the risk of progression and dissemination during periods of intensified immune suppression.     

Sequestration of active Cryptococcus neoformans infection in the parathyroid gland despite prolonged therapy in a renal transplant recipient

Abstract: Disseminated cryptococcal infection occurs mainly in the immunocompromised host, particularly in those with impaired cellular immunity. The treatment outcome depends not only on the duration and choice of antifungal therapy, but also on the activity of the organism to persist in different parts of the body despite therapy. We present a case of persistence of cryptococcal infection in the parathyroid gland in a kidney transplant recipient. A 38-year-old male renal transplant recipient diagnosed to have disseminated cryptococcosis was treated with discontinuation of immunosuppression, amphotericin B, and flucytosine for 2 weeks, and fluconazole subsequently. Dialysis was initiated when graft function deteriorated after discontinuation of immunosuppression. The patient showed no clinical signs of active cryptococcal infection on fluconazole therapy. One year after the diagnosis of cryptococcosis, and still on fluconazole, he underwent parathyroidectomy, for severe secondary hyperparathyroidism. Surprisingly, active cryptococcal infection with necrotizing granulomatous inflammation was demonstrated in the parathyroid, despite being on therapy. This patient illustrates that persistence of fungal infection despite prolonged therapy can occur in unusual sites such as the parathyroid and may be a source for future recurrence and dissemination.     

Pulmonary Cryptococcosis: Atypical Results in the Serum Test for Cryptococcal Antigen

Abstract: Pulmonary cryptococcosis: atypical results in the serum test for cryptococcal antigen. C. Jenkins and A. B. X. Breslin. Aust. N.Z. J. Med., 1982, 12 , pp. 527–530.
Two cases of pulmonary infection with Cryptococcus neoformans are reported. In both patients the cryptococcal antigen titres remained positive following initiation of effective therapy, and despite clinical evidence of resolution of disease. The possible causes for these findings are discussed and it is suggested why this atypical serological response does not necessarily indicate dissemination or active infection.     

Enhanced allergic inflammation and airway responsiveness in rats with chronic Cryptococcus neoformans infection: potential role for fungal pulmonary infection in the pathogenesis of asthma

Although Cryptococcus neoformans is recognized for its ability to cause meningoencephalitis and pneumonia among immunocompromised persons, subclinical pulmonary infection is also common among immunocompetent persons. The significance of this infection is unknown. Using a rat model, we explored the potential for pulmonary cryptococcosis to modify allergic responses and airway reactivity. Our findings indicate that localized pulmonary cryptococcal infection (but not disseminated infection) can exacerbate allergic responses to respiratory challenge with ovalbumin, as measured by total immunoglobulin E levels, ovalbumin-specific immunoglobulin E titers, and eosinophil content of bronchoalveolar lavage fluid. Infection-associated enhancement of allergic responses was not dependent on cryptococcal encapsulation and was partially ameliorated by the administration of fluconazole. Increases in both the number of goblet cells and airway responsiveness, which are also features of reactive airway disease, were also present with pulmonary infection. An examination of lung cytokine levels in the context of active pulmonary infection revealed increased expression of interleukin (IL)-10, tumor necrosis factor- alpha , and IL-13, but not IL-12 or interferon- gamma . In contrast, systemic infection was associated with higher levels of interferon- gamma but lower levels of IL-13. Our studies highlight the potential for localized pulmonary C. neoformans infection to potentiate allergic responses and airway reactivity and suggest a potential role for subclinical pulmonary cryptococcosis in the pathogenesis of asthma.