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PubMed1997

The histological spectrum of chronic necrotizing forms of pulmonary aspergillosis.

Chronic necrotizing pulmonary aspergillosis (CNPA) is a rare locally destructive form of chronic aspergillosis that is recognized as a clinical syndrome, but has been poorly defined histologically. In this study, 10 cases of CNPA were evaluated from a morphological perspective. Three distinct forms of CNPA emerged. One form (n = 4) resembled a necrotizing granulomatous pneumonia centered around a central zone of infarct-like necrosis of parenchyma resulting from angioinvasive aspergillus. The second pattern (n = 4) was that of a granulomatous bronchiectatic cavity with a central fungus ball and subtle tongues of necrosis and inflammation extending into and through the fibrous wall of the cavity. A final form (n = 2) had a bronchocentric granulomatosis-like appearance with a necrotizing granulomatous bronchitis/bronchiolitis associated with luminal necrotic debris and replacement of mucosa by a palisaded histiocytic reaction. Despite the varied histomorphology, all patients survived the aspergillus infection after antifungal therapy and surgical resection. The different forms of pulmonary aspergillosis are briefly discussed, and the differential diagnosis, with particular regard to mycetomas and allergic forms of bronchocentric granulomatosis, is highlighted.

Adult↗

PubMed1995

Invasive aspergillosis in systemic lupus erythematosus.

Invasive aspergillosis is seldomly described in systemic lupus erythematosus. We present two cases of aspergillosis and review 21 cases reported between 1957 and 1994. The typical clinical presentation is fever and cough in a hospitalized SLE patient previously treated with corticosteroids, immunosuppressors, and broad-spectrum antibiotics. Unlike aspergillosis in other conditions, granulocytopenia is uncommon. Chest radiographs show diffuse or patchy infiltration of lung fields. Diagnosis was suspected premortem in 2 patients. Aspergillus fumigatus was identified or isolated in sputum or parenchimal tissues in the majority of cases. Twenty-two patients died (95%). The finding of hyphae in the sputum of a systemic lupus erythematosus patient with a suggestive clinical picture should lead to bronchoscopy, bronchoalveolar lavage, and lung biopsy. Proof of diagnosis will come from the demonstration of hyphae in tissues and isolation of aspergillus from tissue cultures. Long-term therapy with amphotericin B alone or in combination with fluorocytosine or itraconazole may help improve survival.

Adult↗

PubMedDate not supplied

Pulmonary invasive aspergillosis in patients infected with the human immunodeficiency virus: report of two cases.

Patients infected with the human immunodeficiency virus (HIV) have an increased frequency of invasive aspergillosis. We report two cases of invasive pulmonary aspergillosis in patients infected with HIV. Patients had less than 10 CD4 (helper cell) cells/mm3 (2/2), presented with fever (2/2), dyspnea (1/2), and abnormal chest radiograph (2/2). Diagnosis was established by transbronchial biopsy (1/2) and autopsy (1/2). Patients died in spite of treatment with intravenous deoxycholate amphotericin B. Prognosis of invasive pulmonary aspergillosis among patients infected with HIV remains dismal, even with aggressive antifungal treatment.

AIDS-Related Opportunistic Infections↗

PubMed1996

Itraconazole in the treatment of orbital aspergillosis.

BACKGROUND: Sino-orbital aspergillosis is typically treated with surgical debridement and intravenous amphotericin B. Some authors have advocated intraorbital irrigation or injection of amphotericin B in specific cases. METHODS: An immunocompetent patient with recurrent sino-orbital aspergillosis is presented. After failing two attempts at traditional therapeutic modalities, treatment with oral itraconazole was initiated. RESULTS: The patient has had resolution of her sino-orbital disease without recurrence at 10 months of follow-up. CONCLUSION: In immunocompetent patients with orbital aspergillosis, itraconazole should be considered as a treatment option in patients who have recurrent or recalcitrant disease, or in those who cannot tolerate amphotericin B.

Administration, Oral↗

PubMed1989

Experience with itraconazole in cryptococcosis and aspergillosis.

Cryptococcosis and aspergillosis in immunocompromised patients are extremely difficult clinical conditions to manage and treatment with available antifungal drugs often fails. Itraconazole, R-51211, Janssen Pharmaceutica, a new orally absorbed triazole, is a possible alternative drug which is potentially effective and nontoxic. Preliminary experience with 28 patients, eight with cryptococcosis and 20 with aspergillosis, is reported. Of these patients, 16 were immunocompromised (seven with the acquired immune-deficiency syndrome (AIDS), five heart transplant recipients and four with leukaemia or lymphoma). Overall, results of treatment were good (18 in remission, four markedly improved, four moderately improved and two failed). Prevention of relapses of cryptococcosis was obtained in all patients with AIDS on long-term itraconazole monotherapy (3 mg/kg). Treatment of invasive aspergillosis required a higher dosage (about 5 mg/kg) and prolonged administration. Besides its efficacy this antifungal agent allowed outpatient management.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Invasive sinus aspergillosis in apparently immunocompetent hosts.

OBJECTIVES: to describe the clinical, microbiological and pathological features of invasive sinus aspergillosis affecting immunocompetent hosts, and to identify the risk factors for mortality. METHODS: we report three apparently immunocompetent patients with invasive sinus aspergillosis, and review all cases reported in the English literature since 1987, the year in which the triazole antifungal agents were introduced. RESULTS: twenty-nine patients (including three of our own) were identified. The presenting symptoms were non-specific and indistinguishable from viral, bacterial or allergic causes of sinusitis. The findings on computed tomography scan were also non-specific, and histopathology and culture of sinus tissue biopsy had low yield. These factors, along with the mistaken impression that Aspergillus can only affect immunocompromised hosts, frequently delayed the diagnosis. Fifty-nine percent of patients either failed therapy or died. The following factors were associated with a poor prognosis: delayed diagnosis, intracranial extension of infection, and histopathology demonstrating hyphal invasion of blood vessel or tissue. Complete surgical extirpation was the key element of successful therapy; antifungal agents played an adjunctive role. CONCLUSIONS: invasive sinus aspergillosis carries high morbidity and mortality, even in immunocompetent hosts. To improve outcome, the diagnosis must be recognized early, before the organism can invade the central nervous system or vascular structures. Aggressive surgical resection of the infected areas is of utmost importance in the management of this infection.

Adult↗

PubMed1986

Rapid diagnostic methods for aspergillosis.

Conventional laboratory methods are always unsatisfactory for the antemortem diagnosis of systemic mycoses, especially aspergillosis, in immunocompromised patients and those with acquired immune deficiency syndrome (AIDS), regardless of their age. There is increasing proof that aspergillosis is not limited to pulmonary, sinus or nasal regions. These facts, plus the high mortality rate, indicate a tremendous need for reliable and rapid methods of diagnosing this infection. Accordingly, refined techniques such as solid-phase radioimmunoassay (SPIRA), crossed-immunoelectrophoresis (CIE), crossed-radioimmunoelectrophoresis (CRIE), radioallergosorbent test (RAST), radioimmunoprecipitation assay (RIPA), paper radioimmunosorbent test (PRIST), computerized enzyme-linked immunosorbent assay (ELISA), biotin avidin enzyme-linked immunosorbent assay and gas-liquid chromatography (GLC) are being considered or used in clinical laboratories for diagnosing aspergillosis. The advantages and limitations of the RIA, ELISA and GLC methods are briefly discussed.

Antibodies, Fungal↗

PubMed1985

Primary cutaneous aspergillosis in six leukemic children.

We report a cluster of primary cutaneous aspergillosis in six children with hematologic malignancy. When first seen, they had hemorrhagic bullae caused by Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger at the sites of insertion of intravenous cannulas or where arm boards had been taped to the extremities. Rapid diagnosis of cutaneous aspergillosis was made by direct examination of the blister roof with potassium hydroxide before it progressed to a necrotic ulcer. Intravenous amphotericin was instituted promptly in five of six patients, and none died of disseminated aspergillosis. Epidemiologic investigation tracked the source of aspergillus to a storeroom with a false ceiling that had recently been repaired for a water leak.

Amphotericin B↗

PubMed2002

[Non-aggressive diagnostic approach to invasive pulmonary aspergillosis in a hematology unit. Retrospective analysis of a series of 16 cases].

PURPOSE: Among neutropenic patients, diagnosis of invasive pulmonary aspergillosis is difficult. Computed tomographic scan, bronchoalveolar lavage and histology are considered invasive procedures, because they represent an infectious risk for these immunocompromised patients. METHODS: We describe the clinical and noninvasive paraclinical (X-rays, serology) signs of invasive pulmonary aspergillosis, from a retrospective study of 16 cases in a haematology unit. RESULTS: Outside of fever and chills, cough and polypnea are the earliest signs, followed by chest pain, dyspnea, lung auscultation changes, and haemoptysis. The sensitivity of each sign is higher than 56%. Before the onset of lung auscultation changes, the chest X-ray shows mainly unilateral alveolar infiltrates. Sensitivity of serology is weak (25%), but contributed to early diagnosis in 16.6% of cases. CONCLUSION: A better knowledge of the invasive pulmonary aspergillosis clinical, radiological and serological signs could help the practician to prescribe an 'invasive' investigation (computed tomographic scan, bronchoalveolar lavage) to confirm the diagnosis of this fungal infection.

Aspergillosis↗

PubMed1994

[Pulmonary invasive aspergillosis: value of treatment with intravenous amphotericin B administered in a triglyceride emulsion for parenteral usage].

Pulmonary invasive aspergillosis is a frequent and poor prognosis complication of immuno-deficiency and prolonged neutropenia. Its treatment is usually based on amphotericin B (0.7 to 1 mg/kg/d) given as intravenous infusions for at least 2 months. This therapy is limited by the side-effects of the drug including renal failure, myelosuppression, chills and fever. We present here the case of women with pulmonary invasive aspergillosis treated with a different modality of administration. The amphotericin B was given as a continuous infection at 2 mg/kg/d diluted in Intralipid, a triglyceridic mixture used in parenteral nutrition. Given by this way amphotericin B seems to have a good therapeutic efficiency and a mild toxicity limited to transient reduction in creatinine clearance with increased kaliuria. Other current approaches of invasive aspergillosis include the amphotericin B in liposomes, combination of amphotericin B with 5-fluorouracil and the triazolated compounds.

Amphotericin B↗

PubMed2003

[Invasive pulmonary aspergillosis in immunocompromized children: diagnosis and classification].

Invasive aspergillosis is an opportunistic infection, with frequent lung involvement. High-risk children are allogenic bone marrow recipients, and those with hematological malignancies, aplastic anemia or chronic granulomatous disease. Profound and prolonged neutropenia, and corticosteroid therapy are the most important predisposing factors. Building and demolition works represent the major environmental risk factor. The diagnosis of invasive aspergillosis remains difficult to establish. Clinical manifestations are non-specific. Early thoracic computed tomographic scan shows halo sign in most cases. Subsequently appears the air crescent sign. Galactomannan research by sandwich ELISA can be useful in serum and in bronchoalveolar lavage fluid. Aspergillus DNA detection by PCR is still not standardized. Culture of the organism allows species identification. Aspergillus hyphae can be found at cytological examination, but a biopsy specimen is usually required to affirm tissue damage. A new classification of invasive fungal infections in immunocompromised patients was recently proposed by experts from the European Organization for Research and Treatment of Cancer and from the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. On the basis of host linked criteria, microbiological, clinical and radiological features, invasive aspergillosis is classified as proven, probable or possible. These definitions should not be used to guide clinical practice in therapy, but they will improve the quality of epidemiological data, and help the comparison of clinical trial results.

Aspergillosis↗

PubMed1997

Surgery for pulmonary aspergillosis.

OBJECTIVE: Surgery of pulmonary aspergillosis followed by higher incidence of post-operative complications. This was the purpose to evaluate our material. METHODS: Between January 1983 and December 1995, the operation was carried out on a total of 84 patients for pulmonary aspergillosis. The patients were comprised of 71 males and 13 females, with a mean age of 49 years (range, 24-71). Previous lung disorders were observed in about half of the cases (most frequently tuberculosis), while in the other half aspergillosis was developed on the basis of (sub)-acute infections. Haemoptysis was present in 48% of patients. The diagnosis was suspected in 47 cases by chest X-ray. Aspergilloma was diagnosed in 50 patients pre-operatively (excluding 12 typical aspergillomas for cavernostomies), with the other pre-operative diagnoses being tuberculosis, lung cancer, pyoscelrosis, etc. RESULTS: In 71 cases pulmonary resection was carried out (52 lobectomies, 13 wedge resections and six pulmonectomies). A total of 12 cavities were opened by cavernostomy and one lung biopsy was performed for disseminated lung disease. The post-operative mortality rate was 9.5%. The most common complications were bleeding, empyema, bronchial fistula and wound infection. In 23 patients with developed prolonged air leak and/or residual air space, complications were observed more frequently in patients with greater cavitation near the chest wall. CONCLUSIONS: In most cases of pulmonary aspergilloma surgical intervention remains the only effective therapy. The operation has a lower risk factor in asymptomatic patients and in patients without pleural or chest wall involvement. In some cases, cavernostomy may be the only remaining surgical choice.

Adult↗

PubMed2000

Topical amphotericin B application in severe bronchial aspergillosis after lung transplantation: report of experiences in 3 cases.

Ulcerative tracheobronchial aspergillosis after lung transplantation (ltx) may lead to bronchial-pulmonary artery fistula that results in fatal bleeding. We report our early experience with combined systemic, aerolized and topical application of amphotericin B in 3 cases of bronchial aspergillosis after ltx. Two patients are still alive, but 1 died of bleeding from a fistula between the left upper lobe bronchus and the pulmonary artery. Aspergillosis in the second patient resolved with minimal stenosis of the left main and the left upper lobe bronchus, and the third patient developed an anastomotic stenosis that was successfully dilated.

Administration, Inhalation↗

PubMed1999

Native lung pneumonectomy for invasive pulmonary aspergillosis following lung transplantation: a case report.

Pulmonary aspergillosis occurs most commonly as a consequence of immunosuppression in recipients of pulmonary transplantation and is associated with a high mortality. It affects the native lung more commonly than the transplanted lung in single lung transplant patients. Infection often progresses despite aggressive medical therapy. The cornerstone of treatment of acute, semi-invasive, and invasive pulmonary aspergillosis (IPA) is medical, with intravenous amphotericin B, and oral itraconazole either as isolated or combined therapy. While newer, and more expensive liposomal forms of amphotericin B have been used to enhance tissue penetration and minimize renal toxicity, an appreciable improvement in clinical outcome has not been reported. The role of surgery in localized pulmonary aspergillus infection is well recognized, but remains undefined in immunosuppressed patients. We report a case where a pneumonectomy was performed for progressive, refractory angioinvasive aspergillosis in a lung transplant recipient whose disease progressed despite conventional antifungal therapy.

Aspergillosis↗

PubMed2002

Imaging findings in intracranial aspergillosis.

RATIONALE AND OBJECTIVES: The authors' purpose was to elucidate the various computed tomographic (CT) and magnetic resonance (MR) imaging findings in intracranial aspergillosis. MATERIALS AND METHODS: Retrospective analysis of cranial imaging findings was performed in eight proved cases of central nervous system aspergillosis. The patients ranged in age from 17 to 75 years. Four patients were immunocompromised, and four were immunocompetent. CT was performed in all eight patients, and MR imaging in five. RESULTS: Six patients (75%) had multiple lesions seen on the imaging studies, with a total of 27 focal brain lesions demonstrated. The lesions were most commonly seen in the cerebral hemispheres (n = 21), with lesser involvement of the basal ganglia (n = 2) and the posterior fossa (n = 4). Seven lesions were hemorrhagic on CT and/or MR images. There was a correlation between lesion size and hemorrhage, with hemorrhage more likely in larger lesions (>15 mm). At pathologic examination, foci of hemorrhage were noted within both infarcts and abscesses. Enhancement was noted in five lesions, four of which were confirmed abscesses. Contrast enhancement of the lesions was vague and week in immunocompromised patients but solid and strong in immunocompetent patients. There were 18 lesions without hemorrhage or enhancement; they were either infarcts or abscesses at pathologic examination. Some of these small nonhemorrhagic nonenhancing brain lesions in the subcortical white matter mimicked lacunar infarcts. CONCLUSION: Typical imaging findings of intracranial aspergillosis include multifocal lesions involving the cerebral hemispheres, with hemorrhage in approximately 25% of lesions. Lesional contrast enhancement tends to be stronger in immunocompetent hosts.

Adolescent↗

PubMedDate not supplied

Value of antigen and antibody detection, and blood evaluation parameters in diagnosis of avian invasive aspergillosis.

The applicability of ELISA detection of circulating Aspergillus spp. antigen (Ag) and systemic antibody (Ab) of IgG class, and the blood parameter values were evaluated for diagnosis of invasive aspergillosis in Aspergillus spp.-challenged Peking ducks (Anas platyrhynchos). The protective role of Aspergillus spp. IgG was evaluated in Cape shelducks (Tadorna cana) immunized with Aspergillus spp. Ag. Challenged but non-immunized A. platyrhynchos developed invasive aspergillosis on day 21 as demonstrated histopathologically by the presence of fungal micro-granuloma in air sacs and lung tissue, with serum antigenemia fluctuating from 65 to 270 ng of 55-kD basic protein Ag per ml. Immunized A. platyrhynchos did not demonstrate Aspergillus spp. serum antigenemia but did show rare histopathological changes in some air sacs associated with fungal inflammation. Although the differences between immunized and non-immunized T. cana in blood evaluation parameters did not differ significantly, immunized birds mounted high Aspergillus spp.-specific IgG titer. There was no correlation between the blood parameter values and post-immunization timepoints in T. cana and in A. Platyrhynchos. Intramuscular immunization with Aspergillus spp. mycelial phase cultures Ag provided protection against the pathogens. The lack of relations between blood parameter values and increasing Aspergillus spp. IgG titers (in T. cana and A. platyrhynchos) indicate low applicability of these parameters in evaluation of a bird Aspergillus spp. status. Detection of circulating 55-kDa Aspergillus spp. Ag has high early predictive values for invasive aspergillosis in birds.

Animals↗

PubMed2000

Improved outcome of pulmonary aspergillosis in heart transplant recipients with early diagnosis and itraconazole treatment.

Pulmonary aspergillosis is a severe complication in heart transplant recipients. The drug of choice for this infection is amphotericin B, but its use is limited because of its side effects. We observed six cases of pulmonary aspergillosis in a group of 200 patients who had received heart transplants from January 1988 to January 1999. Predisposing factors such as previous rejection, neutropenia and/or cytomegalovirus reactivation were present in all patients. The clinical presentation was characterized by fever and a non-productive cough. X-rays showed monolateral or diffuse infiltrate with or without nodular lesions. The median interval between symptoms and diagnosis was 5 d (range 4-7). Diagnosis was made by culturing trans-tracheal aspirate samples. Aspergillus fumigatus was isolated in 3 patients and A. niger in the other 3. All patients were treated with itraconazole at 200-400 mg/day for 20-60 d and all recovered. One patient treated with the lowest dosage for the shortest term had a recurrence after 1 month and needed a second 30-day course of itraconazole at a higher dosage. No significant side effects were registered. Itraconazole is effective in the therapy of pulmonary aspergillosis, particularly when an early diagnosis is made.

Adult↗

PubMed2000

Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from a hypersensitivity response to Aspergillus fumigatus, although the pathogenesis of the disease is unknown and its prevalence in cystic fibrosis (CF) is still poorly defined. Data from the Epidemiologic Registry of Cystic Fibrosis (ERCF) on 12,447 CF patients gathered from 224 CF centres in nine European countries were analysed. The ERCF definition of ABPA diagnosis is a positive skin test and serum precipitins to A. fumigatus, together with serum immunoglobulin (Ig)E levels >1,000 U x mL(-1) and additional clinical or laboratory parameters. The overall prevalence of ABPA in the ERCF population was 7.8% (range: 2.1% in Sweden to 13.6% in Belgium). Prevalence was low <6 yrs of age but was almost constant approximately 10% thereafter. No sex differences were observed. ABPA affected 8.0% of patients with a deltaF508/deltaF508 genotype and 5-6% with deltaF508/G551D, deltaF508/G542X and deltaF508/N1303K genotypes. ABPA patients presented a lower forced expiratory volume in one second (FEV1) than those without ABPA at any age and the prevalence ranged from 6.6% in patients with FEV1 > or =20-12.9% in those with FEV1 <40%. ABPA was associated with higher rates of microbial colonization, pneumothorax and massive haemoptysis, and with higher IgG serum levels and poorer nutritional status. A mixed model regression analysis of lung function showed that FEVI decline during the follow-up period was not substantially different in ABPA patients compared with non-ABPA patients for any subgroups based on age or disease severity at enrollment. To conclude, allergic bronchopulmonary aspergillosis is a frequent complication in cystic fibrosis patients, particularly after the age of 6 yrs, and it is generally associated with a poorer clinical condition. However, any clear independent influence of allergic bronchopulmonary aspergillosis on the rate of lung function decline in the short term was not shown.

Adolescent↗