Aspergillosis 

Updated: Jan 10, 2019
Author: Eloise M Harman, MD; Chief Editor: Guy W Soo Hoo, MD, MPH 

Overview

Practice Essentials

Aspergillus primarily affects the lungs, causing the following four main syndromes:

  • Allergic bronchopulmonary aspergillosis (ABPA)

  • Chronic necrotizing Aspergillus pneumonia (also termed chronic necrotizing pulmonary aspergillosis [CNPA])

  • Aspergilloma

  • Invasive aspergillosis

However, in patients who are severely immunocompromised, Aspergillus may hematogenously disseminate beyond the lungs.

Signs and symptoms

Allergic bronchopulmonary aspergillosis

  • Occurs in persons with asthma and those with cystic fibrosis (CF)

  • May manifest as fever and pulmonary infiltrates unresponsive to antibacterial therapy

  • Patients often have a cough and produce mucous plugs, which may form bronchial casts; they may have hemoptysis

  • Patients with asthma and ABPA may have poorly controlled disease and difficulty tapering off oral corticosteroids

  • ABPA may occur in conjunction with allergic fungal sinusitis, with symptoms including chronic sinusitis with purulent sinus drainage

  • Wheezing may be noted upon auscultation of the chest; the patient may produce mucous plugs upon coughing

Aspergilloma

  • May manifest as an asymptomatic radiographic abnormality in a patient with preexisting cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes

  • May occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia in patients with HIV infection

  • Causes hemoptysis, which may be massive and life threatening, in 40-60% of patients

  • Less commonly, may cause cough and fever

Chronic necrotizing pulmonary aspergillosis

  • Occurs in patients with underlying disease (eg, steroid-dependent chronic obstructive pulmonary disease [COPD], alcoholism)

  • Manifests as a subacute pneumonia unresponsive to antibiotic therapy, which progresses and cavitates over weeks or months

  • Symptoms may include fever, cough, night sweats, and weight loss

Invasive aspergillosis

  • Occurs in patients with prolonged neutropenia or immunosuppression

  • Typically manifests as fever, cough, dyspnea, pleuritic chest pain, and, sometimes, hemoptysis

  • Patients may be tachypneic and have rapidly progressive hypoxemia

  • Risk factors include organ transplantation, especially bone marrow but also lung, heart, and other solid organ transplants

  • In bone marrow transplant patients, invasive aspergillosis has a bimodal distribution, occurring early with prolonged neutropenia before engraftment and later during high-dose corticosteroid therapy for graft-versus-host disease

  • In patients with leukemia and lymphoma, invasive aspergillosis may occur after chemotherapy-induced bone marrow suppression

  • Invasive aspergillosis is being increasingly observed in patients with COPD on long-term corticosteroid therapy[1, 2]

See Clinical Presentation for more detail.

Diagnosis

Allergic bronchopulmonary aspergillosis

ABPA is defined by abnormalities including the following:

  • Asthma

  • Eosinophilia

  • A positive skin test result for Aspergillus fumigatus

  • Serum IgE level > 1000 IU/dL

  • Positive test results for Aspergillus precipitins (primarily IgG but also IgA and IgM)

  • Minor criteria for diagnosis include positive Aspergillus radioallergosorbent assay test results and sputum culture

Chest radiography results in ABPA may vary from fleeting pulmonary infiltrates to mucoid impaction to central bronchiectasis. Computed tomography (CT) is helpful for better defining bronchiectasis, and images may demonstrate that apparent lobulated masses are mucus-filled dilated bronchi. Areas of atelectasis related to bronchial obstruction from mucoid impaction may be present.

Diagnostic criteria for ABPA in persons with CF include the following:

  • Clinical deterioration, including coughing, wheezing, increased sputum production, diminished exercise tolerance, and diminished pulmonary function

  • Total serum IgE level higher than 1000 IU/mL or a greater than twofold rise from baseline

  • Positive Aspergillus serology (Aspergillus precipitins or Aspergillus -specific IgG or IgE)[3]

  • New infiltrates on chest radiographs or CT scans

Aspergilloma

Aspergilloma does not cause many characteristic laboratory abnormalities. Aspergillus precipitin antibody test results (ie, for IgG) are usually positive.

Imaging study results are as follows:

  • Chest radiographs show a mass in a preexisting cavity, usually in an upper lobe, manifested by a crescent of air partially outlining a solid mass

  • As the patient is moved onto his or her side or from supine to prone, the mass is observed to move within the cavity

  • CT scans provide better definition of the mass within a cavity and may demonstrate multiple aspergillomas in areas of extensive cavitary disease; CT may be performed with the patient in the supine and prone positions to demonstrate movement of the mass within the cavity

Invasive aspergillosis and CNPA

Definitive diagnosis of invasive aspergillosis or CNPA depends on the demonstration of the organism in tissue, as follows:

  • Visualization of the characteristic fungi using Gomori methenamine silver stain or Calcofluor

  • Positive culture result from sputum, needle biopsy, or bronchoalveolar lavage (BAL) fluid (however, a negative result does not exclude pulmonary aspergillosis)

Weekly monitoring of serum levels of galactomannan, a major component of the Aspergillus cell wall, can be used to screen patients who are at high risk for the development of invasive Aspergillus infection.[4, 5] An elevated galactomannan level in BAL fluid may also be helpful for early diagnosis of invasive aspergillosis.

Imaging study results in invasive aspergillosis are as follows:

  • Chest radiographic features are variable, with solitary or multiple nodules, cavitary lesions, or alveolar infiltrates that are localized or bilateral and more diffuse as disease progresses

  • In early disease, CT scans may demonstrate a characteristic halo sign (ie, an area of ground-glass infiltrate surrounding nodular densities)[6, 7]

  • In later disease, CT scans may show a crescent of air surrounding nodules, indicative of cavitation

  • Because Aspergillus is angioinvasive, infiltrates may be wedge-shaped, pleural-based, and cavitary, which is consistent with pulmonary infarction

See Workup for more detail.

Management

Allergic bronchopulmonary aspergillosis

  • Oral corticosteroids (inhaled steroids are not effective)

  • Adding oral itraconazole to steroids in patients with recurrent or chronic ABPA may be helpful.[8, 9, 10, 11]

  • Patients who have associated allergic fungal sinusitis also benefit from surgical resection of obstructing nasal polyps and inspissated mucus; nasal washes with amphotericin or itraconazole have also been employed

Aspergilloma

  • Treatment is considered when patients become symptomatic, usually with hemoptysis

  • Oral itraconazole may provide partial or complete resolution of aspergillomas in 60% of patients

  • Intracavitary treatment, using CT-guided, percutaneously placed catheters to instill amphotericin alone or in combination with other drugs (eg, acetylcysteine, aminocaproic acid), has been successful in small numbers of patients[12]

  • Surgical resection is curative and may be considered for massive hemoptysis if pulmonary function is adequate

  • Bronchial artery embolization may be used for life-threatening hemoptysis in patients unlikely to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying bronchiectasis with or without aspergilloma)[13]

Invasive aspergillosis

  • Preventive therapy and rapid institution of therapy for suspected cases may be lifesaving

  • Prophylactic antifungal therapy and the use of laminar airflow (LAF) or high-efficiency particulate air (HEPA) filtration of patient rooms can be effective

  • Voriconazole – Drug of choice[14]

  • Posaconazole, amphotericin B, or amphotericin B lipid formulations – May be considered as empiric therapy in critically ill patients with possible mucormycosis

  • Caspofungin – In patients who are unable to tolerate, or are resistant to, other therapies[15]

  • If possible, the level of immunosuppression should be decreased

Chronic necrotizing pulmonary aspergillosis

  • Antifungal therapy is with voriconazole or with itraconazole (if expense is an issue), caspofungin, or amphotericin B or amphotericin lipid formulation

  • A prolonged course of therapy with the goal of radiographic resolution is needed

  • Reduction or elimination of immunosuppression should be attempted, if possible

  • Surgical resection may be considered when localized disease fails to respond to antifungal therapy

See Treatment and Medication for more detail.

Background

Aspergillus species are ubiquitous molds found in organic matter. Although more than 100 species have been identified, the majority of human illness is caused by Aspergillus fumigatus and Aspergillus niger and, less frequently, by Aspergillus flavus and Aspergillus clavatus. The transmission of fungal spores to the human host is via inhalation. (See also Dermatologic Manifestations of Aspergillosis, Pediatric Aspergillosis, and Thoracic Aspergillosis Imaging.)

Aspergillus may cause a broad spectrum of disease in the human host, ranging from hypersensitivity reactions to direct angioinvasion. Aspergillus primarily affects the lungs, causing the following four main syndromes:

  • Allergic bronchopulmonary aspergillosis (ABPA)

  • Chronic necrotizing Aspergillus pneumonia (or chronic necrotizing pulmonary aspergillosis [CNPA])

  • Aspergilloma

  • Invasive aspergillosis

However, in patients who are severely immunocompromised, Aspergillus may hematogenously disseminate beyond the lung, potentially causing endophthalmitis, endocarditis, and abscesses in the myocardium, kidney, liver, spleen, soft tissue, central nervous system (CNS), and bone. In addition, Aspergillus is second to Candida species as a cause of fungal endocarditis. Aspergillus -related endocarditis and wound infections occur in the context of cardiac surgery.

ABPA is a hypersensitivity reaction to A fumigatus colonization of the tracheobronchial tree and occurs in conjunction with asthma and cystic fibrosis (CF). Allergic fungal sinusitis may also occur alone or with ABPA. Bronchocentric granulomatosis and malt worker's lung are two hypersensitivity lung diseases that are caused by Aspergillus species, but they are rare.

An aspergilloma is a fungus ball (mycetoma) that develops in a preexisting cavity in the lung parenchyma. Underlying causes of the cavitary disease may include treated tuberculosis or other necrotizing infection, sarcoidosis, CF, and emphysematous bullae. The ball of fungus may move within the cavity but does not invade the cavity wall. However, it may cause hemoptysis.

CNPA is a subacute process usually found in patients with some degree of immunosuppression, most commonly that associated with underlying lung disease, alcoholism, or long-term corticosteroid therapy. Because it is uncommon, CNPA often remains unrecognized for weeks or months and can cause a progressive cavitary pulmonary infiltrate.

Invasive aspergillosis is a rapidly progressive, often fatal infection that occurs in patients who are severely immunosuppressed, including those who are profoundly neutropenic, those who have received bone marrow or solid organ transplants, and patients with advanced AIDS[16] or chronic granulomatous disease. This infectious process is characterized by invasion of blood vessels, resulting in multifocal infiltrates, which are often wedge-shaped, pleural-based, and cavitary. Dissemination to other organs, particularly the CNS, may occur.

Pathophysiology

Aspergillus causes a spectrum of disease, from colonization to hypersensitivity reactions to chronic necrotizing infections to rapidly progressive angioinvasion, often resulting in death. Rarely found in individuals who are immunocompetent, invasive Aspergillus infection almost always occurs in patients who are immunosuppressed by virtue of underlying lung disease, immunosuppressive drug therapy, or immunodeficiency.

Aspergillus hyphae are histologically distinct from other fungi in that the hyphae have frequent septae, which branch at 45° angles. The hyphae are best visualized in tissue with silver stains. Although many species of Aspergillus have been isolated in nature, A fumigatus is the most common cause of infection in humans. A flavus and A niger are less common. This difference in frequency is probably related to the ability of A fumigatus, but not most other Aspergillus species, to grow at normal human body temperature.

Human host defense against the inhaled spores begins with the mucous layer and the ciliary action in the respiratory tract. Macrophages and neutrophils encompass, engulf, and eradicate the fungus. However, many species of Aspergillus produce toxic metabolites that inhibit macrophage and neutrophil phagocytosis. Corticosteroids also impair macrophage and neutrophil function.

Underlying immunosuppression (eg, HIV disease, chronic granulomatous disease, pharmacologic immunosuppression) also contributes directly to neutrophil dysfunction or decreased numbers of neutrophils. In individuals who are immunosuppressed, vascular invasion is much more common and may lead to infarction, hemorrhage, and necrosis of lung tissue. Persons with CNPA typically have granuloma formation and alveolar consolidation. Hyphae may be observed within the granulomata.

Etiology

ABPA is found in people with asthma and/or CF who are allergic to Aspergillus. The thick mucus found in the airways of these patients may make clearing inhaled Aspergillus spores difficult. Additionally, evidence of genetic susceptibility has been reported. Patients who have certain HLA alleles, particularly HLA-DR2, have increased susceptibility to ABPA, whereas HLA-DQ2 appears to be protective.[17]

Risk factors involved in the development of CNPA include underlying pulmonary disease (including COPD, interstitial lung disease, and previous thoracic surgery) and altered immune status due to chronic corticosteroid therapy, alcoholism, collagen-vascular disease, or chronic granulomatous disease.

Aspergilloma typically develops in the context of preexisting cavitary disease. Aspergillomas may develop in patients with invasive aspergillosis or chronic necrotizing Aspergillus pneumonia.

Invasive aspergillosis occurs almost exclusively in patients who are immunocompromised. Neutropenia and corticosteroid therapy are major risk factors. In addition to patients who have undergone transplantation, patients profoundly neutropenic after receiving chemotherapy for hematologic malignancies or lymphoma, children with chronic granulomatous disease, and patients with late-stage HIV disease also are at risk.

Specific risk factors for invasive aspergillosis after bone marrow transplantation include prolonged neutropenia, graft versus host disease, high-dose corticosteroid therapy, disruption of normal mucosal barriers, mismatched or unrelated donor transplants, and the presence of central venous catheters.

Invasive Aspergillus infection in patients without malignancy or prior chemotherapy (who probably are nevertheless not immunocompetent) is most commonly seen in those with critical illness and COPD who are taking long-term corticosteroid therapy.[18]

Epidemiology

United States

Although allergy to Aspergillus, as manifested by a positive skin test reaction to Aspergillus antigen, is present in approximately 25% of people with asthma and 50% of patients with CF, ABPA is much less common. From surveys and an ABPA registry, 0.25-0.8% of people with asthma and approximately 7% of patients with CF are estimated to have ABPA. The incidence of ABPA in people with asthma who are steroid-dependent or have associated central bronchiectasis is higher, estimated at 7-10%.

CNPA is rare. Frequently undetected in life and found at autopsy, the frequency of chronic necrotizing Aspergillus pneumonia may be underestimated.

The frequency of invasive aspergillosis reflects disease states and treatments that result in prolonged neutropenia and immunosuppression. Invasive aspergillosis is estimated to occur in 5-13% of recipients of bone marrow transplants, 5-25% of patients who have received heart or lung transplants, and 10-20% of patients who are receiving intensive chemotherapy for leukemia. Although it has been described in individuals who are immunocompetent, invasive aspergillosis is exceedingly uncommon in this population.

Aspergilloma is not rare in patients with chronic cavitary lung disease and CF. In one survey of patients with cavitary lung disease due to tuberculosis, 17% developed aspergilloma.

International

The incidence of ABPA among people with asthma appears to be higher in Great Britain than in the United States.

Age

The age distribution of aspergillosis is consistent with that of the various comorbid conditions with which it is associated.

Prognosis

The prognosis for ABPA is fairly good in patients with mildly abnormal pulmonary function. However, patients may remain steroid-dependent. If ABPA is detected late, after the establishment of fibrosis, the response to steroids frequently is poor.

The prognosis for patients with invasive pulmonary aspergillosis is poor. Of these patients, 25-60% may respond to antifungal therapy, but the mortality remains high because of the severity of the underlying disease and the need for continued immunosuppressives and steroids in many patients. If patients respond, at least a 50% chance of relapse exists with subsequent courses of immunosuppression. Disease disseminated to the central nervous system carries a mortality of 100%, as does fungal endocarditis without surgery.[19]

Development of triazole resistance has been blamed for eventual loss of control of the disease in patients receiving long-term triazole therapy. Detection of resistance is made difficult by the high frequency of negative cultures, a problem addressed by a study using hypersensitive real-time PCR assays to assess fungal load in BAL and sputum samples. In culture-negative specimens that were PCR-positive, the CYP51A gene (responsible for most triazole resistance) was amplified to reveal resistance markers in 55% of patients with ABPA or chronic pulmonary aspergillosis. The authors suggest a connection between this "remarkably high" rate and limitations to the effectiveness of azole therapy.[20]

Mortality and morbidity

Invasive aspergillosis is associated with significant mortality, with a rate of 30-95%.

Chronic necrotizing Aspergillus pneumonia has a reported mortality rate of 10-40%, but rates as high as 100% have been noted because it often remains unrecognized for prolonged periods.

Aspergilloma is associated with hemoptysis, which may be severe and life threatening.

ABPA may cause problems with asthma control. Repeated episodes of ABPA may cause widespread bronchiectasis and resultant chronic fibrotic lung disease.

 

Presentation

History

The four most common manifestations of Aspergillus lung disease (ie, allergic bronchopulmonary aspergillosis [ABPA], aspergilloma, chronic necrotizing pulmonary aspergillosis [CNPA], and invasive aspergillosis) have quite different clinical manifestations.

Allergic bronchopulmonary aspergillosis

ABPA is a syndrome occurring in asthmatic persons and patients with cystic fibrosis (CF) that results from a hypersensitivity reaction to Aspergillus colonization of the tracheobronchial tree. This syndrome may cause fever and pulmonary infiltrates that are unresponsive to antibacterial therapy.

Patients often have a cough and produce mucous plugs, which may form bronchial casts. They may have hemoptysis. People with asthma who have ABPA may have poorly controlled disease and difficulty tapering off oral corticosteroids. ABPA may occur in conjunction with allergic fungal sinusitis, with symptoms including chronic sinusitis with purulent sinus drainage.

Aspergilloma

Aspergilloma may manifest as an asymptomatic radiographic abnormality in a patient with preexisting cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes. In patients with HIV disease, aspergilloma may occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia. Of patients with aspergilloma, 40-60% experience hemoptysis, which may be massive and life threatening. Less commonly, aspergilloma may cause cough and fever.

Chronic necrotizing pulmonary aspergillosis

CNPA manifests as a subacute pneumonia unresponsive to antibiotic therapy, which progresses and cavitates over weeks or months. Patients with CNPA have underlying disease, such as steroid-dependent chronic obstructive pulmonary disease (COPD) or alcoholism, with symptoms that may include fever, cough, night sweats, and weight loss. Usually, patients have received prolonged courses of antibiotic therapy and sometimes empiric antituberculous therapy without response prior to diagnosis via biopsy or culture.

Invasive aspergillosis

Invasive aspergillosis typically manifests as fever, cough, dyspnea, pleuritic chest pain, and sometimes hemoptysis in patients with prolonged neutropenia or immunosuppression.

Aspergillus infection after organ transplantation most often occurs in bone marrow recipients. However, invasive aspergillosis may be observed in patients who have received lung, heart, and other solid organ transplants. Of these solid organ transplants, lung transplant recipients are at significant risk. In bone marrow transplant recipients, invasive aspergillosis has a bimodal distribution, occurring early with prolonged neutropenia before engraftment and later in the context of high-dose corticosteroid therapy for graft versus host disease.[21] It has also been observed in heart transplant recipients.[7]

In patients with leukemia and lymphoma, aspergillosis may occur after chemotherapy-induced bone marrow suppression, with resultant prolonged neutropenia, manifesting with persistent fever and pulmonary infiltrates despite broad-spectrum antibiotic therapy. Radiographic and CT scan images may reveal characteristic patterns, including nodules, cavitary infiltrates, and focal infiltrates.

Invasive aspergillosis is being increasingly observed in patients with COPD on long-term corticosteroid therapy.[1, 2]

Physical Examination

Physical findings in patients with aspergillosis are nonspecific.

In ABPA, the patient may have fever. Wheezing may be noted upon auscultation of the chest. The patient may produce mucous plugs upon coughing.

In patients with aspergilloma, signs of the underlying lung disease may be noted, including clubbing in patients with CF. Hemoptysis is frequently present.

In CNPA and invasive aspergillosis, the patient is febrile and may have evidence of lung consolidation. Patients may have hemoptysis. Patients with invasive aspergillosis may be tachypneic and have rapidly progressive worsening hypoxemia.

Complications

ABPA may cause atelectasis, asthma exacerbation, and steroid dependence. Recurrent ABPA episodes may result in widespread bronchiectasis and fibrosis.

Hemoptysis is a frequent complication of aspergilloma.

Invasive aspergillosis may result in respiratory failure and death. Massive hemoptysis may occur. Aspergillus may disseminate to other organs, including the central nervous system, kidneys, and heart, and result in multisystem organ failure.

 

DDx

 

Workup

Laboratory Studies

Because Aspergillus infection may cause colonization, allergy, or invasive infection, its manifestations are quite variable and are best considered based on the disease process.

Allergic bronchopulmonary aspergillosis (ABPA) is defined by several abnormalities, including the following:

  • Asthma

  • Eosinophilia

  • Positive skin test result for A fumigatus

  • Marked elevation of the serum immunoglobulin E (IgE) level to greater than 1000 IU/dL

  • Fleeting pulmonary infiltrates

  • Central bronchiectasis

  • Mucoid impaction

  • Positive test results for Aspergillus precipitins (primarily immunoglobulin G [IgG], but also immunoglobulin A [IgA] and immunoglobulin M [IgM])

Minor criteria for diagnosis include positive Aspergillus radioallergosorbent assay test results and culture findings for Aspergillus in sputum.

Diagnostic criteria for ABPA in persons with cystic fibrosis (CF) were revised by the Cystic Fibrosis Foundation. ABPA is considered a definite diagnosis requiring treatment if the following are noted[23] :

  • Clinical deterioration, including cough, wheeze, increased sputum production, diminished exercise tolerance, or diminished pulmonary function

  • Total serum IgE level greater than 1000 IU/mL or a greater than twofold rise from baseline

  • Positive serology results for Aspergillus (Aspergillus precipitins or Aspergillus -specific IgG or IgE)

  • New infiltrates on chest radiographs or computed tomography (CT) scans

Treatment for ABPA is also recommended in patients with CF who have new radiographic findings and symptoms and a change in baseline IgE level to greater than 500 IU/mL.[23]

Definitive diagnosis of invasive aspergillosis or chronic necrotizing Aspergillus pneumonia depends on the demonstration of the organism in tissue.

In the appropriate clinical setting of pulmonary infiltrates in a patient who is neutropenic or immunosuppressed, visualization of the characteristic fungi using Gomori methenamine silver stain or Calcofluor or a positive culture result from sputum, needle biopsy, or bronchoalveolar lavage (BAL) fluid should result in the prompt institution of therapy.

This is especially important after bone marrow transplantation because a positive Aspergillus culture result from sputum has a 95% positive predictive value for invasive disease. However, a negative fungus result from culture of sputum or BAL fluid does not exclude pulmonary aspergillosis because Aspergillus is cultured from sputum in 8-34% of patients and from BAL fluid in 45-62% of patients eventually found by biopsy or autopsy to have invasive disease.

An assay to detect galactomannan, a major component of the Aspergillus cell wall, is available.[4] Patients who are at high risk, such as those who have received stem cell transplants or who have prolonged neutropenia, may be screened for the development of invasive Aspergillus infection by monitoring serum galactomannan levels weekly.[5]

One study of serum galactomannan index (GMI) found that charting early GMI trends during the first two weeks of antifungal therapy can be helpful in predicting clinical outcomes. A reduction in GMI between baseline and week 1 predicted a good clinical response.[24]

The presence of an elevated galactomannan level in BAL fluid may also be helpful in the diagnosis of pulmonary aspergillosis in patients in whom compatible radiographic changes are present and BAL testing is performed in the suspicious area.[25] A meta-analysis and systematic review determined that the measurement of BAL-galactomannan levels may help in diagnosing invasive aspergillosis early.[26]

A study by Luong et al of 150 BAL samples from lung transplant recipients concluded that real-time polymerase chain reaction (PCR) assays could be useful in diagnosis of invasive aspergillosis in high-risk populations. Pan-Aspergillus PCR combined with BAL galactomannan testing was 97% specific and 93% sensitive for invasive pulmonary aspergillosis. Species-specific real-time PCR assays for A fumigatus and for A terreus could be used to rule out or identify the common A fumigatus and the amphotericin B-resistant A terreus.[27]

Aspergilloma does not cause many characteristic laboratory abnormalities. Aspergillus precipitin antibody test results (ie, for IgG) are usually positive.[3]

Imaging Studies

ABPA may cause variable manifestations on chest radiographs, from fleeting pulmonary infiltrates to mucoid impaction to central bronchiectasis. Mucoid impaction of bronchiectatic areas may cause a lobulated infiltrate, which has been likened to a cluster of grapes or a hand in a mitten. CT is helpful for better defining bronchiectasis, and scans may show that apparent lobulated masses are mucus-filled dilated bronchi. Areas of atelectasis related to bronchial obstruction from mucoid impaction may be present.

In aspergilloma, chest radiography reveals a mass in a preexisting cavity, usually in an upper lobe, manifested by a crescent of air partially outlining a solid mass. As the patient is moved onto his or her side or from supine to prone, the mass is typically observed to move within the cavity. CT images provide better definition of the mass within a cavity and may demonstrate multiple aspergillomas in areas of extensive cavitary disease. The scanning may be performed with the patient in the supine and prone positions to demonstrate movement of the mass within the cavity.

In invasive aspergillosis, chest radiographic features are variable, with solitary or multiple nodules, cavitary lesions, or alveolar infiltrates that are localized or bilateral and more diffuse as disease progresses. CT images may be very helpful in the early diagnosis of aspergillosis because they may demonstrate a characteristic halo sign (ie, an area of ground-glass infiltrate surrounding nodular densities).[6, 7] Later disease may show a crescent of air surrounding nodules, indicative of cavitation. Because Aspergillus is angioinvasive, infiltrates may be wedge-shaped, pleural-based, and cavitary, which is consistent with pulmonary infarction.

Other Tests

With ABPA, prick or intradermal skin testing with Aspergillus antigen results in a positive reaction manifested by wheal and flare.

Procedures

In ABPA, mucoid impaction of dilated bronchi can cause a masslike appearance, and patients with ABPA sometimes undergo transthoracic needle aspiration in an effort to obtain diagnostic information.

ABPA may be observed in association with chronic eosinophilic pneumonia or cryptogenic organizing pneumonia (COP), and patients may require transbronchial or open biopsy for diagnosis of unresolving pulmonary infiltrates with or without mucoid impaction. In the proper context, prick or intradermal skin testing to confirm immediate hypersensitivity to Aspergillus should be performed first because a negative skin test result excludes the diagnosis of ABPA.[28]

Procedures that may be helpful for the diagnosis of invasive aspergillosis include the following:

  • Bronchoscopy

  • Needle biopsy

  • Open lung biopsy

At bronchoscopy, BAL in areas of pneumonia may provide evidence for the diagnosis. Transbronchial biopsy may be helpful, but it may not be possible, because patients are often thrombocytopenic because of bone marrow suppression. Peripheral lesions may be amenable to transthoracic needle aspiration and biopsy. Open lung biopsy through a small thoracotomy or by video-assisted thoracoscopy may be the only way to obtain tissue samples large enough to confirm the presence of Aspergillus organisms in tissue.[25, 29]

Histologic Findings

Histopathology and silver staining for persons with invasive aspergillosis demonstrate the characteristic septate hyphae, branching at acute angles, and acute inflammatory infiltrate and tissue necrosis with occasional granulomata and blood vessel invasion. The airways of patients with ABPA contain mucus filled with degenerating eosinophils and typical fungal hyphae. ABPA may occur against a background of chronic eosinophilic pneumonia and bronchiolitis, granulomatous bronchitis, bronchocentric granulomatosis, and, occasionally, COP.

Staging

No staging protocol is used for invasive aspergillosis or aspergilloma. ABPA may be progressive, and the following five stages have been described[30] :

  • Acute disease

  • Remission

  • Exacerbation or recurrence

  • Corticosteroid-dependent asthma

  • End-stage fibrosis

 

Treatment

Medical Care

Treatment of chronic necrotizing pulmonary aspergillosis (CNPA) and invasive aspergillosis differs significantly from treatment of allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma.

Allergic bronchopulmonary aspergillosis

ABPA is a hypersensitivity reaction that requires treatment with oral corticosteroids. Inhaled steroids are not effective.

Adding oral itraconazole to steroids in patients with recurrent or chronic ABPA may be helpful.[8, 9, 10, 11] This may allow more rapid resolution of infiltrates and symptoms, facilitating steroid tapering or lowering the needed maintenance corticosteroid dosage. In CF patients with ABPA, the concomitant use of itraconazole and inhaled corticosteroids may increase the risk of adrenal insufficiency.

Patients who have associated allergic fungal sinusitis benefit from surgical resection of obstructing nasal polyps and inspissated mucus in addition to corticosteroid therapy. Nasal washes with amphotericin or itraconazole have also been employed.

Case reports have described the beneficial use of the anti-immunoglobulin E (IgE) monoclonal antibody omalizumab (Xolair) in patients with ABPA.[31]

Aspergilloma

Treatment of aspergilloma is considered when patients become symptomatic, usually with hemoptysis. Surgical resection is curative but may not be possible in patients with limited pulmonary function. Oral itraconazole may provide partial or complete resolution of aspergillomas in 60% of patients. Successful intracavitary treatment using computed tomography (CT)-guided, percutaneously placed catheters to instill amphotericin (alone or with other drugs, including acetylcysteine and aminocaproic acid) has been reported in small numbers of patients.[12]

Bronchial artery embolization may be used for life-threatening hemoptysis in patients thought to have insufficient pulmonary reserve to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying bronchiectasis with or without aspergilloma).[13] Bronchial artery embolization requires a skilled and experienced radiologist because localizing the abnormal vessel(s) may be challenging. Because the anterior spinal arteries may originate from the bronchial vessels, serious neurologic complications, although rare, may occur.

Chronic necrotizing pulmonary aspergillosis

Treatment of CNPA consists of administration of voriconazole, or, in some cases, itraconazole (if expense is an issue), caspofungin, or amphotericin B or amphotericin lipid formulation. A prolonged course of therapy with the goal of radiographic resolution is required. In addition, reduction or elimination of immunosuppression should be attempted, if possible.

Surgical resection may be considered when localized disease fails to respond to antifungal therapy.

Invasive aspergillosis

Invasive aspergillosis[32, 33] is often rapidly progressive and has a high mortality. Therefore, preventive therapy and rapid institution of therapy in patients in whom invasive aspergillosis is suggested may be lifesaving.

Prophylactic antifungal therapy and the use of laminar airflow (LAF) or high-efficiency particulate air (HEPA) filtration of patient rooms in patients who receive bone marrow transplants and other high-risk patients may prevent invasive aspergillosis. In patients with solid organ transplants, especially lung, in whom Aspergillus is cultured from sputum without evidence of pneumonia (colonization), inhaled amphotericin B may be administered.

When high-risk patients develop a compatible clinical picture, empiric treatment for aspergillosis should be initiated as diagnostic testing is undertaken. Voriconazole is now considered the drug of choice for invasive aspergillosis because of better tolerance and improved survival in comparison with amphotericin.[14]

Posaconazole, amphotericin B, or amphotericin B lipid formulations may be considered as empiric therapy in critically ill patients if the clinical picture, particularly the presence of sinusitis, could be compatible with mucormycosis, because voriconazole is ineffective for Zygomycetes infection. Caspofungin has also been approved for treatment of invasive aspergillosis in patients who are unable to tolerate or are resistant to other therapies.[15] Initial combination therapy is usually not indicated and should generally be reserved for treatment failures.[34, 35]

If possible, the level of immunosuppression should be decreased. For example, patients who are neutropenic may receive growth factors (ie, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor), and patients with certain types of transplants, in which transplanted organ dysfunction will not be life threatening (eg, renal transplant), may have immunosuppressive medications, including corticosteroids, reduced or discontinued.

Combination antifungal therapy is sometimes used for patients whose disease progresses while on single-drug therapy. Concomitant therapy with azole antifungals and amphotericin is controversial because the azole antifungals decrease amphotericin-binding sites and may therefore diminish its effectiveness. Be alert to the possibility of diminished effectiveness of amphotericin in any patient who has received prior treatment with an azole antifungal, including voriconazole, itraconazole, fluconazole, or ketoconazole. Newer antifungal azoles are under study (eg, ravuconazole) and may be available for compassionate use in patients in whom other therapies have failed.

The 100-mg delayed-release formulation of the triazole antifungal posaconazole (Noxafil) is indicated for the prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised patients aged 13 years and older who are at high risk of developing these infections. The tablets are administered as a loading dose of 300 mg twice daily on day 1, followed by a once-daily maintenance dose of 300 mg.[36]

The FDA has approved an intravenous formulation of posaconazole (Noxafil), which is indicated for the prophylaxis of invasive Aspergillus and Candida infections in severely immunocompromised adults who are at high risk of developing these infections. Posaconazole injection is administered as a loading dose of 300 mg twice on the first day of treatment, followed by 300 mg once daily thereafter. Posaconazole is also available as a 100-mg delayed-release tablet and in a 40 mg/mL oral suspension.[37]

In March 2015, the FDA approved isavuconazole (Cresemba) for invasive aspergillosis. It has activity against most strains of the following microorganisms, both in vitro and in clinical infection: Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger. Approval was based on the SECURE study (n = 516) that demonstrated isavuconazole was noninferior voriconazole on the primary endpoint of all-cause mortality at day 42 for the treatment of adult patients with invasive aspergillosis or other filamentous fungi (isavuconazole 18.6% vs voriconazole 20.2%).[38]

Further inpatient care and transfer

Further inpatient care

For invasive aspergillosis, monitor the patient for resolution of fever, hypoxemia, and pulmonary infiltrates. Patients who do not respond to therapy with voriconazole or combination therapy with voriconazole and caspofungin should be seen in consultation by an infectious disease specialist. Monitoring of serum voriconazole levels may be considered in nonresponders.[39] Consider reducing immunosuppression if possible based on the underlying disease. Other considerations include surgical resection for localized disease and the addition of other antifungal agents.

Transfer

Transfer to a tertiary care center may be warranted in patients with aspergilloma or invasive aspergillosis with massive hemoptysis if bronchial artery embolization or surgical resection is considered. Patients with invasive aspergillosis who do not respond to initial antifungal therapy may also benefit from transfer to a center where infectious disease expertise in the management of fungal infections is available.

Surgical Care

Allergic bronchopulmonary aspergillosis

Areas of mucoid impaction in ABPA may have a masslike appearance and are sometimes resected as an undiagnosed lung mass; however, steroid therapy and oral itraconazole therapy are preferred. Allergic fungal sinusitis usually requires endoscopic sinus surgery to improve drainage.

Aspergilloma

Surgical resection may be considered for massive hemoptysis in patients with aspergilloma if pulmonary function is sufficient for this sort of intervention. Assessment of operative risk necessitates obtaining pulmonary function studies, arterial blood gas determinations, and, possibly, split lung function studies (eg, quantitative perfusion lung scanning). Because aspergilloma occurs in cavitary areas, the affected lung may not be functional. Surgical resection may be difficult because of scarring, pleural adhesion, and the presence of abnormal vasculature.

Chronic necrotizing pulmonary aspergillosis and invasive aspergillosis

Surgical resection is a consideration for localized CNPA that has failed to respond to prolonged antifungal therapy.[40] Aspergillomas may occasionally form in areas of necrotizing pneumonia. These necrotic areas may bleed, sometimes massively, necessitating consideration of surgical resection. Patients may be high-risk surgical candidates because of underlying disease, coagulopathy, or thrombocytopenia and limited pulmonary reserve.[19] Age is also a factor.[41] The UK National Aspergillosis Centre noted the need to raise awareness of this disease to encourage drug trials and studies that will result in more effective treatment.[42]

Consultations

Consultation with a pulmonologist may be helpful for patients suggested to have invasive aspergillosis or chronic necrotizing Aspergillus pneumonia in order to establish a definitive diagnosis. Once the diagnosis is established, consultation with an infectious diseases specialist is usually helpful in management, especially if patients do not respond to initial fungal therapy.

Patients with ABPA or allergic fungal sinusitis should be treated by a pulmonologist or allergist familiar with the management of these conditions. Consultation with a pulmonologist is also indicated in patients with aspergilloma. Input from a thoracic surgeon may also be needed if surgical resection is feasible. In selected patients, consultation with an invasive radiologist may be indicated for CT-directed catheter placement to allow intracavitary therapy or bronchial artery embolization.

Prevention

Invasive aspergillosis is frequently fatal, and prevention is the best way to decrease its associated morbidity and mortality. The use of LAF rooms or HEPA filters decreases the concentration of fungi and bacteria in hospital rooms. Use of LAF rooms has been shown to decrease the incidence of invasive Aspergillus infection in patients undergoing bone marrow transplantation.

Prophylactic antifungal therapy indications in high-risk patients

Although fluconazole is not effective against Aspergillus, it significantly decreases the incidence of fungal infections after bone marrow transplantation and is the most frequently used oral prophylactic antifungal therapy[43]

Oral itraconazole has been found to be less effective than fluconazole, probably because of poor bioavailability of the drug in capsule form

Voriconazole is effective as secondary prophylaxis in patients who have been successfully treated for Aspergillus infection and who again require chemotherapy for consolidation or relapse[44] ; however, the use of voriconazole may increase the risk of the patient developing zygomycosis[45]

Posaconazole has been shown to be more effective than fluconazole for preventing invasive Aspergillus infection in patients with graft-versus-host disease (GVHD), though the overall incidence of fungal infections is similar for the two drugs.[23] ; posaconazole is approved for prophylaxis of invasive Aspergillus and Candida infections in high-risk patients, including those with GVHD and prolonged neutropenia from chemotherapy; because posaconazole is a broad-spectrum antifungal agent and widespread use would promote resistance, posaconazole prophylaxis should be limited to patients at highest risk or those with known resistance to other antifungals[46]

Inhaled amphotericin has also been used for prophylaxis, particularly in lung transplant recipients colonized with Aspergillus[47] ; however, results are variable, and concerns have been raised about its effect on lung function[48]

Oral itraconazole appears to be a safe and effective prophylactic antifungal for children with chronic granulomatous disease

Long-Term Monitoring

ABPA is usually managed in an outpatient setting. Serial measurement of the serum IgE level is a useful way to monitor response to therapy and to predict relapse after initial management. Levels are measured every 1-2 months during an exacerbation and every 3 months during remission. The rationale for repeat measurements of IgE levels during clinical remission is that 35% of exacerbations are asymptomatic but may result in lung damage. Elevated IgE levels should be evaluated further with a chest radiograph and institution of therapy with prednisone and possibly itraconazole.

Patients with invasive aspergillosis or CNPA who respond to initial inpatient treatment may require several weeks of antifungal therapy. Oral voriconazole or itraconazole (sometimes chosen because of cost) is administered until clinical and radiographic resolution.

 

Guidelines

Guidelines Summary

Guidelines on the management of aspergillosis by the Infectious Diseases Society of America are as follows[49, 50] :

  • Submit tissue and fluid specimens for histopathologic, cytologic, and culture examination to diagnose invasive aspergillosis. However, molecular techniques, such as DNA sequencing, should be used to identify Aspergillus species in cases that involve either isolates with atypical growth or concern for resistance.
  • If invasive pulmonary aspergillosis is suspected, the guidelines recommend performing CT scanning of the chest, regardless of chest radiography findings. Bronchoscopy with bronchoalveolar lavage is also recommended in such cases, unless significant comorbidities (eg, bleeding, severe hypoxemia) preclude it.
  • Detection of galactomannan (a component of the Aspergillus cell wall) in serum or bronchoalveolar lavage fluid is recommended as an accurate marker for the diagnosis of invasive aspergillosis in adults and children, when used in certain patient subpopulations, such as hematopoietic stem cell transplant recipients or patients with hematologic malignancies.
  • Serum assays for (1 → 3)-β-D-glucan are recommended for diagnosing invasive aspergillosis in high-risk patients (hematologic malignancy, allogeneic hematopoietic stem cell transplant), but are not specific for Aspergillus.
  • If invasive pulmonary aspergillosis is suspected, antifungal therapy should be initiated while diagnostic evaluation is ongoing. Voriconazole is recommended for primary treatment of invasive pulmonary aspergillosis, although combination therapy with voriconazole and echinocandin may be warranted for some high-risk patients.
  • Antifungal therapy for invasive pulmonary aspergillosis should continue for at least 6-12 weeks. Antifungal prophylaxis should also be instituted for patients with prolonged neutropenia who are at high risk for invasive aspergillosis. Prophylactic regimens with posaconazole, voriconazole, and/or micafungin are considered to be most effective.
  • Amphotericin B deoxycholate and its lipid derivatives are appropriate options for initial and salvage therapy of Aspergillus infections when voriconazole cannot be administered. However, amphotericin B deoxycholate should be reserved for use in resource-limited settings in which no alternative agents are available. Lipid formulations of amphotericin B should be considered in settings in which azoles are contraindicated or not tolerated.
  • Aerosolized formulations of amphotericin B may be considered as prophylaxis in patients with prolonged neutropenia (patients receiving induction/reinduction therapy for acute leukemia and allogeneic hematopoietic stem cell transplant recipients following conditioning or during treatment of graft versus host disease) and in lung transplant recipients.
  • Echinocandins are effective in salvage therapy (either alone or in combination) against invasive aspergillosis, but they are not recommended for routine use as monotherapy for the primary treatment of invasive aspergillosis.
  • Triazoles are preferred agents for the treatment and prevention of invasive aspergillosis in most patients.
  • Surgery for aspergillosis should be considered for localized disease that is easily accessible to debridement (eg, invasive fungal sinusitis, localized cutaneous disease).
  • The guidelines recommend that both surgery and either systemic voriconazole or a lipid formulation of amphotericin B be used in invasive Aspergillus fungal sinusitis, but surgical removal alone can be used to treat an Aspergillus fungal ball of the paranasal sinus. Enlargement of the sinus ostomy may be needed to improve drainage and prevent recurrence.
  • Recommend prophylaxis with posaconazole, voriconazole, and/or micafungin during prolonged neutropenia for those who are at high risk for invasive aspergillosis.
  • The guidelines do not recommend routine antifungal susceptibility testing. Instead, it should be reserved for cases in which infection with an azole-resistant isolate is suspected, or in which a patient is unresponsive to antifungal agents.
  • The guideline recommends using the same antifungal agents for the treatment of aspergillosis in children as are used in adults. However, dosing of many of these agents may be different for children. The authors also note that although voriconazole is only approved by the US Food and Drug Administration for children aged 12 years and older, it is the cornerstone of aspergillosis treatment in children of all ages.
  • Suggest a follow-up chest CT scan to assess the response of invasive pulmonary aspergillosis to treatment after a minimum of 2 weeks of treatment; earlier assessment is indicated if the patient clinically deteriorates . When a nodule is close to a large vessel, more frequent monitoring may be required.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology, and the European Respiratory Society Joint Clinical Guidelines are summarized below.[51]

Strongly recommended diagnostic methods are as follows:

  • Chest CT and bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis
  • Direct microscopy, preferably using optical brighteners, histopathology, and culture
  • Pathogen identification to species complex level for all clinically relevant Aspergillus isolates; antifungal susceptibility testing in patients with invasive disease in regions with resistance found in contemporary surveillance programs

Recommended and other diagnostic methods are as follows:

  • Serum and BAL galactomannan measures as markers for the diagnosis of invasive aspergillosis
  • Polymerase chain reaction should be considered in conjunction with other diagnostic tests

Treatment guidance is as follows:

  • Preferred agents for first-line treatment of pulmonary invasive aspergillosis: Isavuconazole and voriconazole
  • Moderately support agent: Liposomal amphotericin B
  • Not recommended: Combinations of antifungal agents as primary treatment option
  • Strongly recommended practice: Therapeutic drug monitoring for patients receiving posaconazole suspension or any form of voriconazole for invasive aspergillosis treatment
  • Strongly recommended practice: In refractory disease, where a personalized approach may consider reversal of predisposing factors, switch drug classes and implement surgical intervention

Prophylaxis recommendations are as follows:

  • Primary prophylaxis with posaconazole strongly recommended in patients with acute myelogenous leukemia or myelodysplastic syndrome receiving induction chemotherapy
  • Secondary prophylaxis strongly recommended in high-risk patients
 

Medication

Medication Summary

The treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) requires intravenous antifungal therapy. Voriconazole is usually first-line therapy, sometimes in combination with other agents, such as caspofungin. Another triazole antifungal agent, isavuconazole, is also indicated for invasive aspergillosis. Amphotericin may sometimes be prescribed in treatment failures.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction treated with corticosteroids. The addition of oral antifungal therapy with itraconazole may be beneficial in the management of ABPA. Aspergillomas may respond to prolonged oral itraconazole therapy. Intracavitary therapy with amphotericin has also been used in small numbers of patients.

Further inpatient and outpatient medications

ABPA therapy includes oral prednisone and, in selected cases, oral itraconazole, usually for several months. As the patient is tapered off oral steroids, inhaled corticosteroids should be added for control of underlying asthma. The concomitant use of inhaled budesonide and oral itraconazole has been found to cause adrenal suppression in a significant proportion of patients with cystic fibrosis (CF) and ABPA.

For aspergilloma, oral itraconazole therapy may be beneficial. A Japanese study found that 60% of patients with aspergilloma had some response to oral itraconazole. In patients with bilateral aspergillomas or severe underlying disease preventing surgical resection, oral itraconazole therapy may be continued for several months.

For invasive aspergillosis and CNPA, specific antifungal therapy with oral or intravenous voriconazole is the usual initial therapy. Response to therapy may be poor. In patients who respond, prolonged therapy may be required.

Antifungal agents

Class Summary

Their mechanism of action may involve increasing the permeability of the cell membrane, which, in turn, causes intracellular components to leak.

Amphotericin B (Abelcet, AmBisome)

Amphotericin B is a polyene antibiotic produced by a strain of Streptomyces nodosus. It can be fungistatic or fungicidal. It binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. Newer lipid formulations are as effective as the original formulation and have less nephrotoxicity. Use may be associated with fever, rigors, and nausea (premedication with hydrocortisone and meperidine may be beneficial). Adequate hydration may decrease nephrotoxicity, and patients who can tolerate fluid should be administered prehydration and posthydration.

Itraconazole (Sporanox, Onmel, Tolsura)

Itraconazole is a synthetic triazole antifungal agent with greater activity against Aspergillus than fluconazole or ketoconazole. It has fungistatic activity. Itraconazole slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

It is available in oral formulations (eg, capsule, suspension) and is useful for prolonged antifungal therapy. A new oral formulation of itraconazole is also available that uses SUBA (SUper-BioAvailable) technology to improve the bioavailability of poorly soluble drugs.

Caspofungin (Cancidas)

Caspofungin is an antifungal with efficacy against A fumigatus,A flavus, and Aspergillus terreus. It is the first of a new class of antifungals called echinocandins. It works on a component of fungal cell walls that is not present in mammalian cells. Caspofungin is indicated for Aspergillus infection in patients who are refractory to or cannot tolerate other therapies. It has not been studied for primary therapy.

Voriconazole (VFEND)

Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. It is a triazole antifungal agent that inhibits fungal cytochrome P-450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Posaconazole (Noxafil)

Posaconazole is a triazole antifungal agent. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

It is available as an oral suspension (200 mg/5 mL), 100-mg delayed-release tablet, and injection. Posaconazole injection is administered as a loading dose of 300 mg twice on the first day of treatment, followed by 300 mg once daily thereafter. The tablets are administered as a loading dose of 300 mg twice daily on day 1, followed by a once-daily maintenance dose of 300 mg.

Isavuconazonium sulfate (Cresemba)

Isavuconazole is a triazole antifungal agent. Isavuconazole is the active moiety of the prodrug isavuconazonium sulfate. It is indicated for invasive aspergillosis and has activity against most strains of the following microorganisms, both in vitro and in clinical infection: Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger.

Corticosteroids

Class Summary

Corticosteroids are useful in the management of allergic reactions. These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

 

Questions & Answers

Overview

What are the main syndromes of aspergillosis?

What are the signs and symptoms of allergic bronchopulmonary aspergillosis (ABPA)?

What are the signs and symptoms of aspergilloma?

What are the signs and symptoms of chronic necrotizing pulmonary aspergillosis (CNPA)?

What are the signs and symptoms of invasive aspergillosis?

How is allergic bronchopulmonary aspergillosis (ABPA) diagnosed?

What are the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in persons with cystic fibrosis (CF)?

How is aspergilloma diagnosed?

How is invasive aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) diagnosed?

Which findings on imaging studies suggest invasive aspergillosis?

What are the treatment options for allergic bronchopulmonary aspergillosis (ABPA)?

What are treatment options for aspergilloma?

What are the treatment options for invasive aspergillosis?

What are the treatment options for chronic necrotizing pulmonary aspergillosis (CNPA)?

What is aspergillosis?

What are complications resulting from aspergillosis?

What is allergic bronchopulmonary aspergillosis (ABPA)?

What is aspergilloma?

What is chronic necrotizing pulmonary aspergillosis (CNPA)?

What is invasive aspergillosis?

What is the pathophysiology of aspergillosis?

What causes aspergillosis?

What is the prevalence of aspergillosis in the US?

What is the global incidence of aspergillosis?

Which factors affect the age distribution of aspergillosis?

What is the prognosis of aspergillosis?

What are the mortality rates for aspergillosis?

Presentation

What is the common clinical manifestation of aspergillosis?

What are the clinical manifestations of allergic bronchopulmonary aspergillosis (ABPA)?

What are the clinical manifestations of aspergilloma?

What are the clinical manifestations of chronic necrotizing pulmonary aspergillosis (CNPA)?

What are the clinical manifestations of invasive aspergillosis?

Which physical findings suggest aspergillosis?

What are the complications of aspergillosis?

DDX

What other conditions should be included in the differential diagnoses of aspergillosis?

What are the differential diagnoses for Aspergillosis?

Workup

What is the basis for lab test selection in the diagnosis of aspergillosis?

Which abnormal lab findings suggest allergic bronchopulmonary aspergillosis (ABPA)?

What are the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in persons with cystic fibrosis (CF)?

Which lab studies are performed in the diagnosis of invasive aspergillosis or chronic necrotizing pulmonary aspergillosis (CNPA)?

What is the role of galactomannan measurement in the diagnosis of invasive aspergillosis?

What is the role of imaging studies in the workup of aspergillosis?

What is the role of skin testing in the workup of aspergillosis?

What is the role of transthoracic needle aspiration in the workup of aspergillosis?

Which procedures may be helpful for the diagnosis of invasive aspergillosis?

Which histologic findings are characteristic of aspergillosis?

How is aspergillosis staged?

Treatment

How is aspergillosis treated?

What are the treatment options for allergic bronchopulmonary aspergillosis (ABPA)?

What are the treatment options for aspergilloma?

What are the treatment options for chronic necrotizing pulmonary aspergillosis (CNPA)?

What are the treatment options for invasive aspergillosis?

Which drugs are used in the treatment of invasive aspergillosis?

What is included in inpatient care of invasive aspergillosis?

When is transfer indicated for the management of aspergillosis?

What is the role of surgery in the treatment of allergic bronchopulmonary aspergillosis (ABPA)?

What is the role of surgery in the treatment of aspergilloma?

What is the role of surgery in the treatment of chronic necrotizing pulmonary aspergillosis (CNPA) and invasive aspergillosis?

Which medical personnel provide consultation to patients with aspergillosis?

How is invasive aspergillosis prevented?

What are the indications of prophylactic antifungal therapy for the prevention of aspergillosis?

What is included in long-term monitoring of patients with aspergillosis?

Guidelines

What are the Infectious Diseases Society of America (IDSA) treatment guidelines for aspergillosis?

What are the ESCMID, ECMM, and ERS joint clinical guidelines for the diagnosis of aspergillosis?

What are the ESCMID, ECMM, and ERS joint clinical guidelines for the treatment of aspergillosis?

What are the ESCMID, ECMM, and ERS joint clinical guidelines for prophylaxis against aspergillosis?

Medications

What is the role of medications in the treatment of aspergillosis?

Which medications in the drug class Corticosteroids are used in the treatment of Aspergillosis?

Which medications in the drug class Antifungal agents are used in the treatment of Aspergillosis?