eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Pneumonia, Fungal: Differential Diagnoses & Workup

Author: Romeo A Mandanas, MD, FACP, Director, Western Oklahoma Blood and Marrow Transplant Program, Site Research Leader, Cancer Care Associates-Oklahoma City
Contributor Information and Disclosures

Updated: Sep 17, 2009

Differential Diagnoses

Acute Respiratory Distress Syndrome
Pneumonia, Viral
Chemical Worker's Lung
Pulmonary Edema, Cardiogenic
Chlamydial Pneumonias
Pulmonary Edema, Neurogenic
Coal Worker's Pneumoconiosis
Pulmonary Fibrosis, Idiopathic
Eosinophilic Pneumonia
Pulmonary Fibrosis, Interstitial (Nonidiopathic)
Pneumocystis Carinii Pneumonia
Tuberculosis
Pneumonia, Aspiration
Pneumonia, Bacterial

Workup

Laboratory Studies

  • CBC count with differential
    • The total WBC count may be elevated in normal hosts with endemic mycoses.
    • Eosinophilia can be observed in the differentials, particularly in persons with coccidioidomycosis.
    • If the patient presents with neutropenia or leukopenia, the possibility of an opportunistic infection with Candida or Aspergillus organisms is increased.
  • Sputum examination and potassium hydroxide stain
    • This study may show fungal hyphae or yeasts, but the results must correlate with the clinical situation because saprophytic colonization occurs in the oropharyngeal or respiratory tract of some patients and may not necessarily indicate invasive infection.
    • Carefully transport, process, and culture specimens that may be contaminated by bacteria, may be saprophytic yeasts endogenous to the oral cavity, and may be airborne Conidia of saprophytic fungi.
  • Blood culture: Obtain this culture to identify Candida species (lysis centrifugation) or B dermatitidis if the patient has disseminated disease.
  • Culture of other fluids: Obtain a urine fungal culture in men after a prostatic massage to identify Cryptococcus species.
  • Nonculture methods for detecting fungal infections: These provide a more rapid and sensitive test when compared with culture methodology. Various antigen detection assays, such as galactomannan enzyme immunoassay for detection of Aspergillus invasive infections, are now in clinical use. Polymerase chain reaction (PCR)–based assays are also available for detecting various pathogens, including Aspergillus, Histoplasma, and Candida species.4
    • Comparison of these assays (antigen detection using enzyme-linked immunosorbent assay [ELISA] or latex agglutination and molecular detection with PCR) show equal specificities for all 3 assays (>97%) in the detection of Candida species. PCR-based assays are most sensitive compared with ELISA and latex agglutination (95%, 75%, and 25%, respectively).
    • For Aspergillus species antigen, galactomannan ELISA assay findings may be positive in the blood very early prior to clinical suspicion of invasive fungal infection and may be of use in monitoring and preemptive treatment in high-risk populations.5,6,7 Using a galactomannan platelia Aspergillus enzyme immunoassay approved by the US Food and Drug Administration, investigators showed that 2 consecutive samples with an optical index of 0.5 provided the highest test accuracy (specificity, 97.5%; sensitivity, 92.1%; positive predictive value, 87.5%; negative predictive value, 98.5%).8 Testing in bronchoalveolar lavage (BAL) fluid increased the sensitivity compared with serum galactomannan assay from 71-100%.9 Care should be taken, however, because false-positive results have been reported in patients taking piperacillin-tazobactam antibiotics and certain intravenous fluids such as plasmalyte.10
    • Beta-glucan testing is also available and may be comparable or more sensitive than galactomannan assays in diagnosing invasive aspergillosis; several kits are available worldwide. False-positive results have also been reported in patients receiving fungal-derived antibiotics and cross-reactions have been reported with Pseudomonas aeruginosa infections.11
    • Aspergillus PCR is most sensitive (100%) when performed on the bronchial lavage fluid of patients with invasive pulmonary aspergillosis, but it is only 40-66% sensitive when performed on the blood. No standardized protocols have been established among laboratories performing this assay.11
    • ELISA or latex agglutination is 70-80% sensitive for identifying H capsulatum and C immitis. PCR for H capsulatum from the bronchoalveolar lavage fluid aids in the rapid detection within 24 hours in a patient with AIDS, and this has been confirmed 10 days later based on the growth and culture isolation of the organism from various tissues.
  • Serology: Utility depends on the individual fungal infectious agent. Antibody detection against C immitis is highly useful, but these tests are of less utility if the pulmonary infection is due to other fungi. Serology testing for blastomycosis provides little clinical diagnostic help because of the insensitivity of testing for this fungus and the antibody cross-reactivity that occurs with other fungal infections.

Imaging Studies

  • Chest radiography
    • Patchy infiltrate, nodules, consolidation, cavitation, or pleural effusion may be observed.
    • Mediastinal adenopathy is common in patients with endemic fungal pneumonias. The adenopathy may be either unilateral or bilateral.
    • Miliary infiltration occurs in patients with disseminated disease.
Chest radiograph showing multiple pulmonary nodul...

Chest radiograph showing multiple pulmonary nodules. The patient was treated with corticosteroids for acute graft versus host disease following bone marrow transplantation for chronic myeloid leukemia. The patient smoked marijuana for 2 weeks prior to this chest radiograph being taken. Bronchoalveolar lavage revealed Aspergillus niger and other species on fungal cultures.

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Chest radiograph showing multiple pulmonary nodul...

Chest radiograph showing multiple pulmonary nodules. The patient was treated with corticosteroids for acute graft versus host disease following bone marrow transplantation for chronic myeloid leukemia. The patient smoked marijuana for 2 weeks prior to this chest radiograph being taken. Bronchoalveolar lavage revealed Aspergillus niger and other species on fungal cultures.

  • Chest CT scanning
    • This imaging study plays a role in the early diagnosis of nonspecific infiltrates in patients who are immunocompromised.
    • High-resolution chest CT scanning allows observation of the halo sign in patients with aspergillosis. This is a nodular lesion usually surrounded by a ground-glass opacity or halo. As many as 61% of 235 patients with invasive aspergillosis were found to have the halo sign in one study.12
    • Obtaining a CT scan of the abdomen and brain may reveal sites of dissemination.
CT scan of a patient with invasive aspergillosis ...

CT scan of a patient with invasive aspergillosis showing multiple lung lesions, some with cavitation.

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CT scan of a patient with invasive aspergillosis ...

CT scan of a patient with invasive aspergillosis showing multiple lung lesions, some with cavitation.


CT scan of aspergillosis of the lungs showing mul...

CT scan of aspergillosis of the lungs showing multiple pleural-based and lung parenchymal lesions. One of the parenchymal lesions on the right gives a suggestion of the halo sign.

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CT scan of aspergillosis of the lungs showing mul...

CT scan of aspergillosis of the lungs showing multiple pleural-based and lung parenchymal lesions. One of the parenchymal lesions on the right gives a suggestion of the halo sign.

  • MRI of lung lesions: This study may reveal the hemorrhagic content of Aspergillus lesions.

Procedures

  • Fiberoptic bronchoscopy (procedure of choice) is used to obtain bronchial lavage specimens for staining and culture techniques and transbronchial biopsy specimens for identification of fungal tissue invasion. This procedure reveals positive results in 75-90% of endemic mycoses, shows a 50-90% yield in cryptococcal disease, and shows varying yields in Aspergillus and Candida infections, for which clinical correlation is still important.
  • Perform transthoracic fine-needle aspiration of nodules to access lesions that are short of an open lung biopsy.
  • Occasionally, performing an open lung biopsy is the only way to prove invasive disease for Aspergillus or Candida organisms; however, this procedure may be difficult to perform in patients with severe neutropenia and thrombocytopenia who are in respiratory failure.
  • Perform a lumbar spinal puncture in patients with suspected cryptococcosis or disseminated disease with CNS symptomatology.
  • Conduct a bone marrow aspiration and biopsy if the patient has persistent fever or suspected disseminated disease or if the patient has hematologic findings such as thrombocytopenia or neutropenia.

Histologic Findings

Biopsy specimens show the following:

  • Caseating or necrotizing granulomas with intracellular organisms inside macrophages (eg, H capsulatum, C immitis)
  • Fungal hyphae in infection with Aspergillus and Mucor species
  • Intracellular yeast organisms in Candida species infections

More on Pneumonia, Fungal

Overview: Pneumonia, Fungal
Differential Diagnoses & Workup: Pneumonia, Fungal
Treatment & Medication: Pneumonia, Fungal
Follow-up: Pneumonia, Fungal
Multimedia: Pneumonia, Fungal
References
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Further Reading

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Keywords

fungal pneumonia, pulmonary mycosis, mycotic pneumonia, , endemic fungal pneumonia, aspergillosis, meningoencephalitis, cryptococcosis, acute leukemia, lymphoma, myeloablative chemotherapy, bone marrow transplantation, peripheral blood stem cell transplantation, allogeneic stem cell transplantation, unrelated donor transplantation, graft-versus-host disease, graft versus host disease, solid organ transplantation on immunosuppressive treatment, prolonged corticosteroid therapy, AIDS, congenital immune deficiency syndromes

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Contributor Information and Disclosures

Author

Romeo A Mandanas, MD, FACP, Director, Western Oklahoma Blood and Marrow Transplant Program, Site Research Leader, Cancer Care Associates-Oklahoma City
Romeo A Mandanas, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Oklahoma State Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Ryland P Byrd Jr, MD, Professor, Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University; Chief of Pulmonary Medicine, Medical Director of Respiratory Therapy, Intensive Care Unit, Program Director of Pulmonary Diseases and Critical Care Medicine Fellowship, James H Quillen Veterans Affairs Medical Center
Ryland P Byrd Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Southern Medical Association
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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