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Improved survival in central nervous system aspergillosis: a series of immunocompromised children with leukemia undergoing stereotactic resection of aspergillomas. Report of four cases.

Central nervous system (CNS) aspergillosis remains a daunting diagnosis. This opportunistic mycosis historically carries a mortality rate approaching 100% in immunocompromised patients, with death ensuing within days after the onset of neurological symptoms. From their literature review, the authors concluded that children contracting CNS aspergillosis while undergoing systemic chemotherapy for leukemias represent a particularly unfortunate prognostic group. Antifungal medications prove ineffective for treating CNS aspergillosis in patients immunocompromised because of their chemotherapy regimens. In contrast, withholding chemotherapy to reverse immunosuppression, thereby improving the efficacy of antifungal medications, allows for progression of the primary leukemic disease. The authors present a series of four immunosuppressed patients whose course of treatment for leukemia was complicated by CNS Aspergillus sp. abscesses. Multiple cerebral fungal abscesses developed in two patients and a single cerebral abscess developed in two. All four patients underwent frameless stereotactic resection of the aspergilloma. All children later experienced resolution of their CNS infections and full neurological recovery. At 2- to 4-year follow ups, one patient has died of leukemia and the other three continue to thrive without evidence of recurrent aspergillosis. Given the grave natural history cited in the literature for this disease when medical treatment is instituted alone, the authors stress the crucial role of stereotactic neurosurgery for the intelligent treatment of immunocompromised children suspected of harboring a CNS aspergilloma abscesses. The authors propose that the goal for successful treatment in these patients should be gross-total resection of the abscess, its wall, and its capsule.

Adolescent↗

Aspergillosis of the central nervous system: a catastrophic opportunistic infection.

The clinical features and outcome of the treatment of aspergillosis of the central nervous system (CNS) in Thai patients are presented. The patients who were diagnosed as having CNS aspergillosis by tissue biopsy or culture from January 1, 1991 to December 31, 2000 were retrospectively reviewed. The study variables including age, sex, underlying disease, symptoms and signs, neuro-imaging studies, pathological findings and outcome of treatment, are described. There were seven cases of aspergillosis of the central nervous system. Four patients were male. The median age was 65 years (range 36-78 years). The most common underlying disease was diabetes mellitus (4/7; 57.1%). Two patients (28.6%) had no underlying disease. The most common primary site of infection was the paranasal sinuses (6/7; 85.7%). The most common clinical presentation was headache (6/7; 85.7%). Common neurological signs included multiple cranial nerve palsies (5/7; 71.4%) and alteration of consciousness (3/7; 42.9%). The median duration of the symptoms prior to admission was 60 days (range 8-180 days). All patients were treated with intravenous antifungal agents at high doses. Extensive surgery was performed in 6 patients. The mortality rate was very high (6/7; 85.7%). The median time from diagnosis and treatment to death was 53 days (22-720 days). Aspergillosis of the CNS should be considered in those with clinical features of headache, multiple cranial nerve palsies and alteration of consciousness accompanied by sinusitis, especially in elderly and diabetic patients. It remains a catastrophic opportunistic infection in spite of the current intensive and aggressive treatment.

Adult↗

[Invasive aspergillosis in Castilla y Leon and Cantabria: years 1998 and 1999].

BACKGROUND: Invasive aspergillosis (IA) is a life-threatening mycosis showing a fast clinical course, affecting immunosupressed people particularly patients suffering leukemia or following organ transplantation programs. The aim of this work is to show epidemiologycal concerns about IA in Castilla y Leon and Cantabria: the disease's incidence, the main clinical presentations, the underlaying diseases and diagnostic rules in the laboratory. PATIENTS AND METHODS: 50 cases of IA were obtained from the countries of Castilla y Leon and Cantabria in a two-years (1998-1999) retrospective study. Epidemiology, clinical and diagnostic features including the 14 main institutions were registered and accounted in a single data base. RESULTS: The majority of IA cases were recorded in major institutions possessing haematology units or organ transplantation programs. Invasive pulmonary aspergillosis was the main feature (39/50 cases) showing serious underlying diseases (25/50 cases) or following organ transplantation programs (15/50 cases). Certain diagnosis was obtained for only ten cases of invasive pulmonary aspergillosis and eleven cases of extrapulmonary stages of IA. In a high number of cases (44/50 cases) conventional microbiological procedures (42/50 showing positive cultures) were developed. Serology investigations were undertaken in eight cases. Serological issues relying on anti-Aspergillus antibodies showed no diagnostic value. Aspergillus fumigatus was the most common species involved in IA (33/44 cases). CONCLUSIONS: A low incidence of the disease in this country was reported: with 50 cases in 14 hospital institutions during a two-year period. We observed most cases in large hospital centres performing transplant operations. Invasive pulmonary aspergillosis was the main clinical setting in immunosupressed patients. Microbiology diagnostic issues relied on conventional methods in particularly on culture.

English Abstract↗

Ocular aspergillosis isolated in the anterior chamber.

BACKGROUND: In all cases in which ocular involvement has been reported in endogenous aspergillosis, the posterior segment of the eye was involved. METHODS: The authors examined a patient who had been intubated and treated with corticosteroid therapy for status asthmaticus and in whom a mass later developed in the anterior chamber of the right eye. RESULTS: Computed tomography showed a solitary lesion in the left lower pulmonary lobe and multiple brain lesions that enhanced with contrast. Aspergillus fumigatus was cultured from the endotracheal tube. However, ocular and blood cultures were negative, as were the results of a bone marrow biopsy, lung biopsy, and anterior chamber paracentesis. Disseminated aspergillosis was confirmed when a biopsy of the anterior chamber mass was performed, and results of histopathologic examination showed the presence of hyphae. The patient responded to a regimen of antifungal drugs. CONCLUSION: This is the first known reported case in which the diagnosis of disseminated aspergillosis was confirmed with biopsy of an anterior chamber mass. This case demonstrates that Aspergillus organisms may disseminate to the anterior chamber of the eye without involving the posterior segment.

Adult↗

Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species. METHODS: We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. RESULTS: Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received >or=1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. CONCLUSION: Caspofungin demonstrated usefulness in the salvage treatment of IA.

Adolescent↗

The rapid development of an aspergilloma secondary to allergic bronchopulmonary aspergillosis.

A patient with allergic bronchopulmonary aspergillosis who developed a cavitary lung lesion suggestive of neoplasm is presented. At thoracotomy an aspergilloma was found. Although coexistence of these two forms of aspergillosis has been reported, the brief history of preceding asthma and the rapid development of the aspergilloma in the absence of typical roentgenographic features are unusual. Aspergilloma should be considered when a patient with allergic bronchopulmonary aspergillosis develops a cavitary pulmonary lesion.

Aged↗

Itraconazole in the treatment of aspergillosis: a study of 16 cases.

Itraconazole, a new triazole antifungal agent, has marked in vitro activity against filamentous fungi, particularly Aspergillus. We studied three groups of patients suffering from aspergillosis (16 cases): six affected with aspergilloma, three with allergic bronchopulmonary aspergillosis and seven with invasive aspergillosis. The survey consisted in clinical, radiological, mycological and serological evaluations with respect to drug plasma levels. Itraconazole was given at a dosage of 200-400 mg day-1 for periods ranging from 14 to 488 days. Out of the 16 patients, nine responded to therapy (recovery or improvement) and one failed to respond. Three patients improved but experienced relapses and three others could not be evaluated because of liver function disorders, so that treatment had to be stopped prematurely.

Adolescent↗

Trial of ketoconazole in non-invasive pulmonary aspergillosis.

A one year study of the efficacy of the antifungal agent ketoconazole in non-invasive pulmonary aspergillosis was carried out. Ten patients, seven with allergic bronchopulmonary aspergillosis and three with mycetoma, were studied. They were randomly allocated to receive 400 mg daily or placebo orally in a double blind fashion. In the treated group (n = 6), concentrations of serum IgG specific for Aspergillus fumigatus fell significantly during treatment (mean reduction 42% (SEM 2.2%) compared with determinations preceding the study). This effect was evident by three months and continued for the 12 months of treatment. Patients receiving placebo (n = 4) showed no significant change in serum IgG concentration (mean change + 10% (SEM 5.3%]. Asthmatic patients treated with ketoconazole (n = 4) had significantly lower symptom scores than those receiving placebo (n = 3) (+0.45%/month (SEM 6.9%) versus +27%/month (SEM 6.5%); p less than 0.001). None of the patients treated with ketoconazole reported any adverse effects. Ketoconazole may cause serious liver damage but its use may be justified in bronchopulmonary aspergillosis if further experience confirms its ability to alter the course of a potentially serious disease.

Adult↗

Thoracic manifestations of aspergillosis.

The fungus Aspergillus can cause a variety of pulmonary disorders. Allergic bronchopulmonary aspergillosis is characterized by eosinophilic pulmonary infiltrates, bronchiectasis and bronchial mucus plugs, and can progress to chronic pulmonary fibrosis. There are four additional variant forms of allergic bronchopulmonary aspergillosis, which may or may not be associated with aspergillus hypersensitivity. They are mucoid impaction of bronchi, pulmonary infiltrates with eosinophilia, bronchocentric granulomatosis, and extrinsic allergic alveolitis. Intracavitary aspergilloma (mycetoma, or fungus ball) is a noninvasive Aspergillus colonization of virtually any type of preexisting pulmonary cavity or cystic space. Invasive pulmonary aspergillosis is a serious, usually fatal infection in patients being treated with immunosuppressions or who have chronic (malignant or nonmalignant) debilitating disease. Diagnosis of Aspergillus-caused pulmonary disorders is based on a combination of clinical, laboratory, and radiographic findings, all of which should be known to the radiologist.

Aspergillosis↗

Pulmonary aspergillosis: imaging findings with pathologic correlation.

Pulmonary involvement with Aspergillus fumigatus is varied and largely dependent on the patient's underlying pulmonary and immune status. Hypersensitivity reactions from inhalation of spores can cause acute allergic alveolitis, and bronchial colonization can cause allergic bronchopulmonary aspergillosis (ABPA). The latter is found mainly in patients with asthma or cystic fibrosis. Mycetomas develop from secondary colonization of preexisting lung cavities. Invasive and semi-invasive aspergillosis affect mostly patients with altered immune status. This essay illustrates the radiologic findings of pulmonary aspergillosis and shows the correlation between the imaging and pathologic findings.

Aspergillosis↗

[Pulmonary aspergillosis: variable appearances (pictorial essay)].

Pulmonary aspergillosis can present in different clinical, pathological and radiological forms depending on the patient's immunological status and underlying pulmonary disease. Allergic bronchopulmonary aspergillosis, aspergilloma, invasive and semi-invasive forms can be recognized. In this article, we review the radiological findings of different forms of pulmonary aspergillosis.

Aspergillosis↗

[Clinical pictures of pulmonary aspergillosis].

Pulmonary infection with Aspergillus can present a variety of clinical manifestations. Essentially, allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis are the three main forms. The coexistence of more than one of these entities is not unusual. Predisposing factors for such mycotic infections include previous lung-structure damage, immunodeficiency, and disturbances in the equilibrium of the resident flora of the respiratory tract. The radiological changes in pulmonary aspergillosis are described in association with clinical presentations and laboratory findings and are demonstrated by actual examples.

Aspergillosis↗

High-resolution computed tomography and pathologic findings in pulmonary aspergillosis: a pictorial essay.

Aspergillus can cause a wide spectrum of pulmonary complications. It may colonize pre-existing cavities to form mycetomas. In asthmatic patients it may lead to a hypersensitivity reaction involving eosinophilic infiltration of the bronchial wall and mucoid impaction (a condition called allergic bronchopulmonary aspergillosis) or granulomatous inflammation (bronchocentric granulomatosis). In the immunocompromised host, Aspergillus may invade blood vessels, causing hemorrhagic infarction (angioinvasive aspergillosis), or it may cause tracheobronchitis, bronchiolitis or pneumonia (airway invasive aspergillosis), as well as abscess formation with or without adjacent tissue invasion. Each of the manifestations of Aspergillus infection has a distinct histologic and high-resolution computed tomography (CT) appearance. This pictorial essay reviews the characteristic high-resolution CT and corresponding pathologic findings of pulmonary complications due to Aspergillus fumigatus.

Adolescent↗

Cutaneous aspergillosis and acquired immunodeficiency syndrome.

BACKGROUND: Primary cutaneous aspergillosis is an uncommon finding in patients with acquired immunodeficiency syndrome (AIDS); only 13 cases have been reported in the literature. OBSERVATIONS: We describe 11 patients with primary cutaneous aspergillosis and AIDS. There does not seem to be an age, sex, race, or human immunodeficiency virus risk factor predisposition. This is a late manifestation of AIDS; patients typically have low CD4 counts (<0.050 x 10(9)/L [<50/microL]) and other AIDS-defining illnesses. The most frequent presentation is in patients with cytomegalovirus disease and neutropenia caused by ganciclovir therapy. Lesions developed at the site of occlusive dressings for an indwelling intravenous catheter site in 10 patients. Neutrophil counts may be normal at the time of diagnosis. A minor presentation is in the patient without neutropenia as a result of traumatic inoculation. Histological findings and/or culture results are required for diagnosis. Patients develop cutaneous lesions despite prophylactic therapy with fluconazole. Lesions can be treated with excision and lifelong therapy with itraconazole. CONCLUSION: Because of the potential morbidity and mortality of cutaneous aspergillosis, a high level of suspicion and prompt institution of therapy is required.

Acquired Immunodeficiency Syndrome↗

Sino-orbital aspergillosis in acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical features, causes, imaging characteristics, treatment, and outcome of patients with the acquired immunodeficiency syndrome (AIDS) and sino-orbital aspergillosis. DESIGN: Records of 5 patients were reviewed. Results of imaging and histopathologic examinations and clinical courses of the patients were studied. RESULTS: There were 3 women and 2 men (mean age, 34.0 years). All had received a diagnosis of AIDS, and mean CD4+ cell count was 0.014 x 10(9)/L (14 cells/mm3). Computed tomographic scanning exhibited heterogeneous, enhancing sino-orbital soft tissue lesions with bony erosion, and magnetic resonance imaging disclosed soft tissue masses hypointense on T1- and T2-weighted images. The infection involved 1 or more paranasal sinuses, with extension into the right orbit in 3 patients and into the left orbit in 2. Patients were treated with aggressive surgical debridement and intravenous antifungal agents. In addition, local irrigation of amphotericin B was performed in 3 patients. Aspergillus fumigatus was found to be the cause in all 5 patients. Intracranial extension developed in 4 patients, and all subsequently died. The 2 longest surviving patients were the only ones being treated with protease inhibitors. Three patients had a history of frequent marijuana smoking. CONCLUSIONS: Sino-orbital aspergillosis is a progressive, relentless, and usually fatal opportunistic infection of advanced AIDS. Patients are first seen with long-standing headache and proptosis with minimal external inflammatory signs. Marijuana smoking may increase the risk for development of sino-orbital aspergillosis in these patients. Aggressive surgical and medical treatment, combined with newer combination therapies using protease inhibitors, may improve the longevity of these patients.

AIDS-Related Opportunistic Infections↗

Left vocal cord paralysis as a primary manifestation of invasive pulmonary aspergillosis in a nonimmunocompromised host.

We report the first case (to our knowledge) of vocal cord paralysis as a primary manifestation of invasive pulmonary aspergillosis, which occurred in a 69-year-old woman without immunodeficiency. Her chest radiograph showed left upper lobe infiltration with pleural thickening, and a computed tomogram of her chest showed a thick pleural reaction and fibrosis around the arch of the aorta. A transbronchial biopsy specimen revealed Aspergillus infection. The patient was treated with oral itraconazole. However, since vocal cord paralysis persisted, the patient underwent type I thyroplasty to improve vocal function. A review of the literature showed that the incidence of invasive pulmonary aspergillosis has increased, even in nonimmunocompromised subjects, and that the disease has a potential for recurrent laryngeal nerve palsy. Therefore, invasive pulmonary aspergillosis should be considered in patients with vocal cord paralysis.

Administration, Oral↗

Successful treatment of invasive aspergillosis complicating prolonged treatment-related neutropenia in acute myelogenous leukemia with amphotericin B lipid complex.

Herein we report the successful treatment of invasive aspergillosis with the liposomal amphotericin B (AMB) formulation, Amphotericin B Lipid Complex (ABLC). This investigational compound was employed in a 50-year-old patient with acute myelomonocytic leukemia complicated by prolonged, treatment-induced granulocytopenia and documented Aspergillus flavus sinusitis with signs of disseminated aspergillosis. The patient demonstrated radiographic signs of pulmonary aspergillosis and biochemical signs of hepatic involvement that were resistant to a 23 day course of conventional AMB (Fungizone) therapy. Following therapy with ABLC her fever abated, her chest X-ray findings improved, and her hepatic function tests improved with eventual resolution.

Adult↗

A case of chronic necrotizing pulmonary aspergillosis due to Aspergillus nidulans.

A 55-year old man without immunosuppression clinically showed a coin lesion in the right lower lung on the chest radiographs. Aspergillus nidulans was isolated and identified in both trans-bronchial lung biopsy specimen and resected tissue. The specimens revealed characteristics of chronic necrotizing pulmonary aspergillosis pathologically. Very few reports on cases of pulmonary aspergillosis due to A. nidulans exist, and we were not able to find any reports of similar cases. This case may be the first reported case of chronic necrotizing pulmonary aspergillosis due to A. nidulans.

Adenocarcinoma↗