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
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)
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.
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)
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.
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
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)
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
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
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.