eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Aspergillosis: Differential Diagnoses & Workup

Author: Eloise M Harman, MD, Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Mar 7, 2008

Differential Diagnoses

Acute Respiratory Distress Syndrome
Nocardiosis
Allergic and Environmental Asthma
Nosocomial Pneumonia
Asthma
Pneumonia, Bacterial
Bronchiectasis
Pneumonia, Fungal
Eosinophilia
Pneumonia, Viral
Eosinophilic Pneumonia
Pulmonary Embolism
Granulocytopenia
Pulmonary Eosinophilia
Heart Transplantation
Renal Transplantation (Medical)
Heart-Lung Transplantation
Sarcoidosis
Hypersensitivity Pneumonitis
Tuberculosis
Liver Transplantation
Wegener Granulomatosis
Lung Abscess
Zygomycosis
Mucormycosis
Mycetoma
Myocardial Abscess

Other Problems to Be Considered

Mucoid impaction
Septic pulmonary emboli

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.

  • ABPA is defined by several abnormalities, including asthma, eosinophilia, a 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, and positive test results for Aspergillus precipitins (primarily immunoglobulin G [IgG], but also immunoglobulin A and immunoglobulin M, antibodies). 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 CF were recently revised by the Cystic Fibrosis Foundation. ABPA is considered a definite diagnosis requiring treatment if the following are noted: (1) clinical deterioration, including cough, wheeze, increased sputum production, diminished exercise tolerance, or diminished pulmonary function; (2) total serum IgE level greater than 1000 IU/mL or a greater than 2-fold rise from baseline; (3) positive serology results for Aspergillus (Aspergillus precipitins or Aspergillus -specific IgG or IgE); and (4) new infiltrates on chest radiographs or 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.4
  • 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.5 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.6 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.7
  • Aspergilloma does not cause many characteristic laboratory abnormalities. Aspergillus precipitin antibody test results (ie, for IgG) are usually positive.

Imaging Studies

  • 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 scan 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).8 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.
  • ABPA may cause variable manifestations, 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 scanning is helpful for better defining bronchiectasis, and images 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 observed to move within the cavity. CT scan 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.

Other Tests

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

Procedures

  • Procedures that may be helpful for the diagnosis of invasive aspergillosis include bronchoscopy, needle biopsy, and 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.7,9
  • For 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 bronchiolitis obliterans-organizing pneumonia (BOOP), 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.

Histologic Findings

Histopathology and silver staining for persons with invasive aspergillosis demonstrates 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 on a background of chronic eosinophilic pneumonia and bronchiolitis, granulomatous bronchitis, bronchocentric granulomatosis, and, occasionally, BOOP.

Staging

No staging protocol is used for invasive aspergillosis or aspergilloma. ABPA may be progressive, and the following 5 stages have been described10 :

  • Acute disease
  • Remission
  • Exacerbation or recurrence
  • Corticosteroid-dependent asthma
  • End-stage fibrosis

More on Aspergillosis

Overview: Aspergillosis
Differential Diagnoses & Workup: Aspergillosis
Treatment & Medication: Aspergillosis
Follow-up: Aspergillosis
References
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Further Reading

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Keywords

aspergillosis, fungus, fungal infection, inhalational fungal disease, mold infection, invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, ABPA, chronic necrotizing pulmonary aspergillosis, CNPA, chronic necrotizing Aspergillus pneumonia, aspergilloma, mycetoma, fungus ball, disseminated aspergillosis, fungal endocarditis, Aspergillus fumigatus, A fumigatus, Aspergillus niger, A niger, Aspergillus flavus, A flavus, Aspergillus clavatus, A clavatus, bronchocentric granulomatosis, malt worker's lung

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Contributor Information and Disclosures

Author

Eloise M Harman, MD, Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine
Eloise M Harman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Medical Women's Association, American Thoracic Society, Phi Beta Kappa, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Oleh Wasyl Hnatiuk, MD, Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences
Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H, Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine
Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine
Disclosure: Keck School of Medicine, USC None None

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

 
 
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