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PubMed2005

Hard palate perforation due to invasive aspergillosis in a patient with acute lymphoblastic leukemia.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunosuppressed patients. Primary oral invasive aspergillosis is a rare condition. We present an acute lymphoblastic leukemia (ALL) patient with hard palate perforation due to invasive aspergillosis. Two months after the appearance of the fungal lesions, perforation of the hard palate was seen despite amphotericin-b and itracanazole therapy. After debridement of necrotic tissue the patient was followed for spontaneous closure for 6 months but it was seen that the fistula persisted despite the disappearance of the infection. The patient was operated for closure of the palatal fistula and there was no recurrence in 6 months of follow up. Surgical and medical management was performed successfully. Invasive oral aspergillosis is a potentially lethal disease and it should be considered in immunosuppressed patients with oral lesions.

Aspergillosis↗
PubMed2004

A case of primary cutaneous aspergillosis in a renal transplant recipient.

UNLABELLED: Opportunistic fungal infections are life-threatening complications which are a major cause of morbidity and mortality in immunocompromized hosts such as those who have undergone organ transplantation. Aspergillosis comprises a spectrum of disease caused by a ubiquitous saprophytic mold. Invasive aspergillus is a serious life-threatening complication in immunocompromised hosts. Primary cutaneous aspergillosis occurs relatively less frequently and is poorly characterized. We report a case of cutaneous aspergillosis in a 51-year-old renal transplant recipient, which was successfully treated with local excision and concomitant antifungal therapy. CASE: A 51-year-old male renal transplant recipient presented with cutaneous nodules on the dorsum of the right hand. He underwent renal transplantation for end-stage renal disease due to adult dominant polycystic kidney disease (ADPKD) 3 years prior. Initially he suffered an acute rejection episode that was treated with steroid pulse and OKT3 therapy. Eventually he was stabilized on a combination of tacrolimus, prednisone, and mycophenolate mofetil. Three years after transplantation, he developed painless multiple (largest one 5 x 3 cm sized) nodules on the dorsum of his right hand. He was afebrile with no systemic symptoms. A skin biopsy showed a dense solid infiltration of giant cells, histiocytes, and lymphoplasma cells admixed with intra- and extracellular fungal hyphae and spores. The hyphae were septate and acute angle branching, which was consistent with aspergillosis. Oral itraconazole 200 mg/d for 5 weeks was ineffective. Treatment with liposomal amphotericin B for 4 weeks was initiated and MMF was discontinued. The medication was well tolerated with no hepatotoxic effects. Although new lesions did not appear, existing ones did not significantly improve after 4 weeks of treatment. Therefore, most lesions were excised surgically and liposomal amphotericin B continued for 2 weeks followed by treatment with oral fluconazole for 2 months. Ten moths later there was no evidence of recurrence.

Antifungal Agents↗
PubMed2001

Endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared with aspergillosis.

PURPOSE: To describe clinical and/or histopathologic features that could help distinguish endogenous Candida endophthalmitis from endogenous Aspergillus intraocular inflammation and to provide histologic documentation of intraocular spread of these agents. METHODS: Twenty-five patients who underwent enucleation, 13 with morphologic features and/or positive culture for Aspergillus and 12 with histologic evidence and/or positive culture for Candida were included in the study. Clinical information was sought from each case. Patients with AIDS were excluded. The enucleated globes were analyzed to detect location of the fungi, vascular invasion by these agents, and inflammatory response. RESULTS: Candida endophthalmitis was noted in patients with a history of gastrointestinal surgery, hyperalimentation, or diabetes mellitus, whereas aspergillosis was present in patients who had undergone organ transplantation or cardiac surgery. Histopathologically, the vitreous was the primary focus of infection for Candida, whereas subretinal/subretinal pigment epithelium infection was noted in eyes with aspergillosis. Retinal and choroidal vessel wall invasion by fungal elements was noted in cases of aspergillosis but not in cases with candidiasis. Both infectious agents induced suppurative nongranulomatous inflammation. CONCLUSIONS: Unlike Candida endophthalmitis, aspergillosis clinically presents with extensive areas of deep retinitis/choroiditis, and vitreous biopsy may not yield positive results. Histopathologically, it appears that Aspergillus grows preferentially along subretinal pigment epithelium and subretinal space. This intraocular infection is usually associated with a high rate of mortality caused by cerebral and cardiac complications.

Adult↗
PubMed1998

Surgical therapy for pulmonary aspergillosis in immunocompromised patients.

BACKGROUND: Medical management for invasive pulmonary aspergillosis (IPA) is often unsatisfactory. Antifungal therapy may be unable to eradicate IPA in the immunocompromised or neutropenic patient. METHODS: We retrospectively reviewed the surgical management of IPA in 13 immunocompromised patients at our institution. Twelve patients underwent perioperative bone marrow transplantation (4 autologous, 8 allogenic). All 13 patients received antifungal therapy. Eleven patients were neutropenic at the time of operation. RESULTS: The mean interval from diagnosis of aspergillosis to operation was 42 days (range, 3 to 135 days). Eighteen operations were performed on the 13 patients. Seven patients had resections from multiple pulmonary sites, whereas 6 had a single lesion resected. The average lesion resected was 3.7 cm in greatest diameter (range, 1 to 9 cm). After a mean follow-up of 21 months (range, 0 to 9 years), 3 patients (23%) are alive with no evidence of aspergillosis, 6 patients (46%) died without evidence of aspergillosis, and 4 patients (31%) died secondary to aspergillus infection. All 4 patients who died of aspergillus infection received an allogenic bone marrow transplantation. Two patients with direct extrapulmonic extension of IPA at time of operation died of recurrent aspergillus infections. Three of 4 patients who died of aspergillus infection had an absolute neutrophil count less than 1,300 cells/microL at time of operation. The mean absolute neutrophil count of the patients who cleared the aspergillus infection was 5,538 cells/microL. The mean survival of allogenic bone marrow transplant recipients was 5.2 months, and for recipients of autografts was 51.4 months. CONCLUSIONS: In this series, surgical resection of IPA cleared the aspergillus infection in 69% of the patients. Neutropenia, extrapulmonic extension of IPA, and allogenic bone marrow transplantation may predict a worse prognosis. Surgical resection of IPA in immunocompromised patients is an effective form of therapy in a properly selected patient population.

Adolescent↗
PubMed1994

Treatment of invasive aspergillosis.

Invasive aspergillosis is generally a life-threatening invasive opportunistic mycosis affecting principally the upper and lower respiratory tract. Therapeutic response rates vary considerably from one host group to another with particularly high mortality rates in bone marrow transplant, liver transplant and patients with aplastic anaemia or AIDS. Only two drugs are useful for therapy, amphotericin and itraconazole. Recent advances in the formulation of amphoterin B (AmBisome and Amphocil) have resulted in intravenous preparations with lower toxicity, particularly nephrotoxicity, but it has yet to be shown that they have an increased therapeutic index for the treatment of invasive aspergillosis. Itraconazole can only be used orally and in some particularly high-risk or critically ill patients adequate serum concentrations cannot be achieved. The addition of flucytosine or rifampicin to amphotericin B therapy has, at best, only a marginal benefit. Surgery is essential for some manifestations of invasive aspergillosis. This article reviews therapeutic strategies including criteria for initiation of therapy, combination and sequential therapy, duration of therapy and secondary prophylaxis and indications for surgery in invasive aspergillosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pathological features of invasive oral aspergillosis in patients with hematologic malignancies.

PURPOSE: Little is known about the characteristic macroscopic and microscopic changes that take place during the progression of oral invasive aspergillosis in immunocompromised patients. The aim of this study was to determine the relationship between the oral and histopathologic findings in these patients. Such a study would aid in understanding the early development of subsequent progression of the disease. PATIENTS AND METHODS: Twelve patients with hematologic malignancies who developed invasive oral aspergillosis were studied. The condition was divided into three stages according to the oral findings at the time biopsy procedures were performed. Tissue sections from biopsy specimens were stained with hematoxylin and eosin for histopathologic study and the findings were evaluated in relation to the oral findings. Fungal cultures of biopsy specimens were also performed to confirm the causative organisms. RESULTS: The diagnosis of oral aspergillosis was established in terms of both histologic and microbiologic evidence in all 12 patients. In the early stage (three patients), isolated areas of violaceous marginal gingiva consisted of degenerated epithelium and connective tissue infiltrated by fungal hyphae. In the advanced stage (four patients), the violaceous marginal gingiva had become transformed into gray necrotic lesions that extended to the attached gingiva. The necrotic lesions showed ulceration and were covered by a pseudomembrane containing fungal hyphae. At the base of the ulcers, connective tissue was occupied by proliferating fungal hyphae, with vascular invasion being observed. In the late stage (five patients), the ulcerated lesions had progressed, showing destruction of the alveolar bone and surrounding facial muscles, with infiltration of fungal hyphae unto the tissues. No inflammatory cellular reaction was observed until the hematologic status of the patients improved. CONCLUSION: These findings indicate that invasive oral aspergillosis has three distinctive clinicopathological stages. Recognition of the different stages of invasive Aspergillus infections is helpful for correct diagnosis of the disease.

Adult↗
PubMed1999

Epidemiology of nosocomial fungal infections: invasive aspergillosis and the environment.

The incidence rates of invasive aspergillosis have increased dramatically during the last two decades, and, despite all diagnostic and therapeutic efforts, outcome is often fatal. Therefore, preventive measures are of major importance in the control of invasive aspergillosis, and require full understanding of the epidemiology of this devastating disease. The environment has been suggested to play a crucial role in the epidemiology of invasive aspergillosis. Aspergillus spores are released in the air and may remain airborne for prolonged periods. As a result, spores are ubiquitously found in air and contaminate anything in contact with air. It has been hypothesized that the inhalation of airborne Aspergillus spores, either directly or through intermediate nasopharyngeal colonization, is a direct cause of pulmonary infection in immunocompromised patients. Recently, water has been suggested as an additional source of "airborne" Aspergillus spp. This review summarizes the current knowledge on the role of the environment in the epidemiology of invasive aspergillosis.

Air Microbiology↗
PubMed1999

Predictive value of a positive nasal swab for Aspergillus sp. in the diagnosis of invasive aspergillosis in adult neutropenic cancer patients.

To evaluate the value of a positive nasal swab for Aspergillus in the diagnosis of invasive aspergillosis, we prospectively evaluated nasal colonization in 173 episodes of neutropenia in 92 patients with hematological malignancies. Weekly nasal swabs were taken, and the patients were followed until death or resolution of neutropenia. The outcome variables were the development of invasive aspergillosis, empirical antifungal therapy and death. In 31 episodes of neutropenia (18%) there was at least one positive nasal swab for Aspergillus sp. Only two patients developed invasive aspergillosis, both with a positive nasal swab (p = 0.03). The positive and negative predictive values of a nasal swab were 6.4% and 100%, respectively. There was no difference between patients with positive or negative swabs regarding antifungal therapy or death. In this population of patients, a nasal swab for Aspergillus sp. had a low positive predictive value and a high negative predictive value for invasive aspergillosis.

Adolescent↗
PubMed1993

[Invasive aspergillosis in surgical intensive care patients].

Aspergillosis is a rare event in intensive care patients. Three cases of invasive aspergillosis due to Aspergillus fumigatus were diagnosed in a surgical critical care unit. Risk factors for aspergillosis were found in two liver transplanted patients. One of them had a primitive cutaneous aspergillosis, and the other, treatment difficulties due to the unavailability of an injectable preparation of itraconazole, a new triazole antifungal agent efficient against Aspergillus species. The third case occurred in a patient who had had surgery for gastric carcinoma with liver metastasis. The mycological examination of the air and workbench in the patients' rooms disclosed between 2 and 13 CFU.mm-3 of different Aspergillus species. Plasma itraconazole concentrations were measured in one patient only. They were below the therapeutic range, probably because of intestinal disturbances. The oral administration of itraconazole capsules through gastro-intestinal feeding tubes results in a poor availability of the drug. Such a technique of administration should therefore be undertaken with larger doses than those commonly recommended. Moreover, itraconazole plasma concentrations should be monitored. The association with amphotericin B is recommended until normal intestinal absorption has been obtained.

Adult↗
PubMed1998

Myelopathy resulting from invasive aspergillosis.

Aspergillus, a ubiquitous mold, may cause invasive and fatal disease in immunosuppressed patients. Myelopathy is an uncommon presentation of invasive aspergillosis. This report describes three children admitted to the hospital between 1988 and 1995 who developed myelopathy as the first evidence of invasive aspergillosis. All had advanced leukemia and were profoundly immunosuppressed because of chemotherapy and broad-spectrum antibiotics. Weakness and pain presented first; then, sensation to pain and temperature was lost 2 to 6 days later, followed by complete myelopathy. Multiple brain lesions were seen on magnetic resonance imaging in one patient. Despite antifungal therapy, aspergillosis proved fatal within 1 month of onset of myelopathy in all patients. Physicians caring for immunocompromised children should be aware of myelopathy as a presentation of invasive aspergillosis.

Adolescent↗
PubMedDate not supplied

Invasive intracardiac aspergillosis with widespread embolization.

Intracardiac extension of pulmonary aspergillosis is uncommon. We report a case of a patient with chronic necrotizing pulmonary aspergillosis without clinical evidence of cardiac disease in whom transthoracic echocardiography revealed an intracardiac mass. A subsequent transesophageal examination clearly defined a large and complex mass in the left atrium and pulmonary artery. Autopsy performed after cardiopulmonary arrest confirmed the presence of direct cardiac invasion of pulmonary aspergillosis with widespread embolization. This case illustrates the possibility of direct intracardiac extension of pulmonary aspergillosis and the value of transesophageal echocardiography in establishing the diagnosis.

Aspergillosis↗
PubMed2002

Invasive pulmonary aspergillosis: effects of early resection in a neutropenic rat model.

OBJECTIVE: Invasive pulmonary aspergillosis is frequent in neutropenic patients. Usually localized in the beginning, the disease spreads and mortality is high despite antifungal treatment. The role of early adjuvant surgery is not clear. Surgery may help to confirm fungal disease, may control fungal disease locally and may prevent systemic spreading. This study examines effects of early resection on survival and dissemination in a rat model of localized invasive pulmonary aspergillosis. METHODS: Forty persistently neutropenic male albino rats were challenged with standardized conidial aspergillus inoculum injected into peripheral lung tissue of the right upper lobe under direct vision. Animals were divided into four groups. Twenty animals were treated with amphotericin B at 1 mg/kg per day beginning 48 h after inoculation, 20 animals were left untreated. In each group half the animals underwent early resection of localized invasive aspergillosis by lobectomy. Animals were checked daily and mortality was recorded up to 28 days after which surviving animals were sacrificed. RESULTS: Significantly higher survival was observed in resected animals in the non-Am B groups (survival: 10 +/- 19% without early resection and 50 +/- 32% with early resection; P = 0.044). However, early resection did not lead to improved survival in animals treated with amphotericin B (survival 70 +/- 29% without early resection and 50 +/- 32% with early resection; P = 0.316). CONCLUSIONS: In this rat model of localized invasive pulmonary aspergillosis effects of early resection on survival could be demonstrated only in animals not receiving amphotericin B treatment.

Amphotericin B↗
PubMed2006

Invasive pulmonary aspergillosis with cerebral abscess in a patient with idiopathic thrombocytopenic purpura.

Invasive aspergillosis is a devastating infection in immunocompromised hosts. The lung is the most common site of primary infection, and the central nervous system is the most common secondary site of invasive disease. Invasive aspergillosis in autoimmunopathies treated with corticosteroids has rarely been reported in the literature. Herein, we report the case of a 48-year-old female patient with idiopathic thrombocytopenic purpura complicated with fatal invasive pulmonary and cerebral aspergillosis. She had been given 1,016 g intravenous amphotericin B empirically for lung infection during a previous admission. At presentation, she had fever, cough, and shortness of breath for 4 weeks. Chest radiography revealed a huge cavity over the left upper lung field. Bronchoscopic biopsy and culture showed Aspergillus species. She was initially treated with intravenous amphotericin B (0.9 mg/kg/day), and intravenous hydrocortisone for her idiopathic thrombocytopenic purpura. However, deterioration of consciousness occurred 12 days after hospitalization. Computed tomography of the brain showed ring-like cystic mass lesions in the right side basal ganglion. Stereotactic aspiration of the brain revealed Aspergillus species. Her condition exacerbated despite combination treatment with high-dose amphotericin B (1.2 mg/kg/day) and itraconazole (400 mg/day). She died 24 days after admission. This case suggests that treatment with corticosteroids and premature discontinuation of antifungal drugs bear the risk of fatal cerebral involvement in patients with invasive pulmonary aspergillosis.

Amphotericin B↗
PubMed1985

An outbreak of invasive aspergillosis among allogeneic bone marrow transplants: a case-control study.

Between April 1982 and March 1983, 10 of 26 (38.4%) allogeneic bone marrow transplant recipients housed on a newly opened bone marrow transplant unit developed invasive aspergillosis. By contrast, between September 1977 and March 1982, only 3 of 46 (6%) transplant recipients developed invasive aspergillosis. A case-control study to identify host factors related to Aspergillus infection found that aspergillosis was more common in patients with chronic myelogenous leukemia and aplastic anemia, older patients, patients having cytomegalovirus disease, patients who experienced prolonged granulocytopenia, patients conditioned with ara-C (100-200 mg/day), and patients who received longer duration of antimicrobial therapy. A series of logistic regression analyses revealed that underlying disease was the single best predictor of Aspergillus infection. This study demonstrates that underlying disease is an important risk factor for aspergillosis and that special measures may be warranted when transplanting certain patients.

Adult↗
PubMed1999

Concomitant renal and prostatic aspergillosis.

Aspergillosis limited to the urinary tract is a rare disease seen most often in patients with altered immune status. Only 19 cases of renal aspergillosis including 3 with AIDS and 4 cases of isolated prostatic aspergillosis have been reported. We report the first case of concomitant renal and prostatic aspergillosis in a non-immunocompromised patient who presented with pyrexia of unknown origin and with dysuria. The diagnosis was based on the demonstration of characteristic hyphal elements on direct microscopy and isolation of the fungus in the culture of pus from the kidney. In view of obstructive prostatic enlargement and left non-functioning renal mass, transurethral resection of the prostate and left nephrectomy were performed in a single session with successful outcome. The aetiopathogenesis and brief review of the literature are discussed.

Aspergillosis↗
PubMed2001

Aspergillosis in lung transplantation: incidence, risk factors, and prophylactic strategies.

Invasive aspergillosis remains a significant cause of morbidity and mortality in transplantation, especially lung and allogeneic bone marrow transplant recipients. The epidemiology, classic and newly recognized risk factors, and incidence of aspergillosis are reviewed. Risk factors include environmental exposures, airway colonization, profound immunosuppression, neutropenia, prior cytomegalovirus infection, and renal dysfunction. Clinical and radiographic presentations of invasive aspergillosis are discussed, including some unusual manifestations in lung transplant recipients. Early and accurate diagnosis of aspergillosis remains a challenge, and diagnostic strategies are reviewed, with an emphasis on the chest computerized tomography scan and on transbronchial or open lung biopsy. Recent advances include prophylactic and pre-emptive antifungal strategies, newer therapeutic agents, and improved risk stratification.

Antibiotic Prophylaxis↗
PubMed2003

Primary aspergillosis affecting the tongue of a leukemic patient.

We describe a case of primary aspergillosis involving the tongue of a patient with acute myeloid leukemia. Intraoral aspergillosis is very rare and we found only 23 cases reported in the English literature. Clinically it was a 2-cm, ulcerated, grayish lesion on the dorsum of the tongue. Microscopically there was invasion of the epithelium, connective tissue and muscle of the tongue by fungal hyphae branching at 45 degrees angle. The large hyphae were easily seen by H & E stain, and were strongly positive for periodic acid-Schiff and Grocott methenamine. The patient was successfully treated with intravenous amphotericin B. Based on clinical, microscopic and culture data, the diagnosis of primary aspergillosis of the tongue was established. Invasive oral aspergillosis is a potentially lethal disease and it should be considered in immunosuppressed patients.

Acute Disease↗
PubMed1997

Esophageal aspergillosis after bone marrow transplant.

The prolonged immune suppression associated with bone marrow transplants predisposes to fungal infections including Aspergillus. Disseminated aspergillosis occurs in up to 60% of patients with invasive pulmonary aspergillosis; sites of involvement include the brain, gastrointestinal tract, kidney, liver, thyroid, heart, and spleen. There is only one report of isolated esophageal aspergillosis. A recent acute myelogenous leukemia patient had isolated esophageal aspergillosis after bone marrow transplantation which was successfully treated with amphotericin B.

Adult↗