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Pneumocystis (carinii) jiroveci Pneumonia: Differential Diagnoses & Workup

Author: Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Coauthor(s): Shelley A Gilroy, MD, Clinical Professor of Medicine, State University of New York Upstate; Medical Director, Infection Control, University Hospital and Crouse Hospital, Syracuse; Frederick Burton Rose, MD, FACP, Professor, Department of Medicine, University Hospital Epidemiologist, State University of New York Upstate Medical University; Joseph C McLean, MD, Staff Physician, Department of Internal Medicine, William Beaumont Army Medical Center; Clinton Murray, MD, Program Director, Infectious Disease Fellowship, San Antonio Uniformed Services Health Education Consortium; Tanya S Schreibman, MD, Consulting Staff, Department of Internal Medicine, Bach and Godofsky; Michael Rigsby, MD, Director of HIV Care Program, VA Connecticut Healthcare System, West Haven Campus; Associate Professor, Department of Internal Medicine, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Nov 20, 2009

Differential Diagnoses

Acute Respiratory Distress Syndrome
Cytomegalovirus
Lymphocytic Interstitial Pneumonia
Mycoplasma Infections
Pneumonia, Viral
Pulmonary Embolism

Other Problems to Be Considered

Legionellosis
Tuberculosis
Mycobacterium avium complex (MAC) infection

Workup

Laboratory Studies

  • Lactic dehydrogenase study as part of the initial workup
    • Lactic dehydrogenase (LDH) levels are usually elevated (>220 U/L) in patients with P carinii pneumonia (PCP).
    • This study has a high sensitivity (78-100%).
    • The LDH level is elevated in 90% of patients with PCP who are infected with HIV.
    • This study has a much lower specificity because other disease processes result in an elevated LDH level.
    • LDH levels appear to reflect the degree of lung injury.
    • Consistently elevated LDH levels during treatment may indicate therapy failure and a worse prognosis.
    • LDH levels should decline with successful treatment.

Imaging Studies

  • Chest radiography should be obtained in any immunocompromised patient with fever and/or respiratory signs or symptoms. Findings include the following:
    • The chest radiographic findings may be normal in patients with early mild disease.
    • Diffuse bilateral infiltrates extending from the perihilar region are visible in most patients with PCP.
    • Less-common findings include patchy asymmetric infiltrates and pneumatoceles.
    • Pleural effusions and intrathoracic adenopathy are rare.
    • Pneumothorax may develop in patients using aerosolized pentamidine.
    • Apical disease may also be found in patients using aerosolized pentamidine for prophylaxis.

    • Chest radiograph demonstrating diffuse bilateral ...

      Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.

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      Chest radiograph demonstrating diffuse bilateral ...

      Chest radiograph demonstrating diffuse bilateral infiltrates in a patient with Pneumocystis carinii pneumonia.

  • High-resolution CT scanning of the chest
    • High-resolution CT scanning of chest (HRCT) is helpful when the chest radiography findings are equivocal.
    • The typical appearance is patchy areas of ground-glass attenuation with a background of interlobular septal thickening.
    • HRCT yields a high sensitivity for PCP in patients with HIV infection.
    • Negative (normal or unchanged) CT scan findings alone do not rule out PCP.

    • CT scan of chest, with classic patchy areas of gr...

      CT scan of chest, with classic patchy areas of ground-glass attenuation.

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      CT scan of chest, with classic patchy areas of gr...

      CT scan of chest, with classic patchy areas of ground-glass attenuation.

  • Gallium 67 scanning
    • Gallium 67 scan demonstrates an increased diffuse symmetrical pulmonary uptake in patients with PCP.
    • This study is highly sensitive (nearly 100%).
    • The specificity is low (some studies report as low as 20%).
    • The high cost and 2-day time delay in obtaining results have limited its use.
    • A gallium 67 scan is potentially more useful in patients with suspected relapse, as bronchoalveolar lavage (BAL; see Procedures) may be less diagnostic in such cases.

Other Tests

  • Pulmonary function tests should be obtained as part of the initial noninvasive workup in patients with suspected PCP.
    • Results may demonstrate a decreased diffusion capacity of carbon monoxide (DLCO) of less than 75% predicted.
    • Decreased DLCO has a high sensitivity (89-100%) but poor specificity (53%).
    • PCP is unlikely if DLCO is normal.
    • When combined with normal or unchanged HRCT findings, pulmonary function tests may be used to identify patients unlikely to have PCP; such patients may be managed with observation alone.
  • Pulse oximetry on room air should be measured in all patients. The oxygen saturation should be measured both at rest and with exertion. If any hypoxemia is found (O2 saturation <90%), then an arterial blood gas (ABG) level should be obtained to evaluate the need for possible adjunctive corticosteroids (see Medications).

Procedures

  • Obtain sputum sample by sputum-induction for histopathologic testing if PCP is strongly suspected. Pneumocystis organisms are frequently found in sputum induced by inhalation of a hypertonic saline solution.
    • Expectorated sputum has a very low sensitivity and should not be submitted for diagnosis.
    • Sputum induction is the quickest and least-invasive method for definitively diagnosing PCP.8
    • Sensitivity varies widely (<50% to >90%) and depends on proficiency in using the technique and the experience of the laboratory.
    • Specificity is high (99-100%).
    • This study may be less sensitive in patients without HIV infection, as the immunodeficiency caused by HIV infection typically leads to a greater alveolar load of Pneumocystis organisms.
    • It may also be less sensitive in patients receiving aerosolized pentamidine for prophylaxis.
  • BAL is the most common invasive procedure used to diagnose PCP.
    • BAL has a diagnostic yield that exceeds 90% (may be increased if multiple lobes are sampled).9
    • Obtain BAL if PCP is strongly suspected and the induced sputum sample findings are negative.
    • BAL yields a lower sensitivity in patients receiving aerosolized pentamidine, in which case a transbronchial biopsy may be performed in conjunction with BAL.10
    • BAL may be used in patients who are unable to cooperate with an induced sputum sample (eg, because of altered mental status).
    • BAL may be less useful in cases of suspected PCP relapse (see Imaging Studies).
  • Open lung biopsy is the most invasive procedure and yields 100% sensitivity and specificity because it provides the greatest amount of tissue for diagnosis. However, this procedure is reserved for rare cases when bronchoscopy findings are nondiagnostic.

Histologic Findings

Because clinical and radiologic findings are not specific for PCP and because P jiroveci cannot be grown in vitro, histopathologic demonstration is necessary before a definitive diagnosis is established. The following are the staining techniques available for respiratory tract secretions:

  • Cresyl violet, Giemsa, Diff-Quik, and Wright stain are used to detect both the trophozoite and cyst forms but not the cyst wall (see Image 1).

  • Diff-Quik stain demonstrating <em>Pneumocystis ji...

    Diff-Quik stain demonstrating Pneumocystis jiroveci.

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    Diff-Quik stain demonstrating <em>Pneumocystis ji...

    Diff-Quik stain demonstrating Pneumocystis jiroveci.

  • Methenamine silver, toluidine blue, and Gram-Weigert selectively stain the wall of Pneumocystis cysts (see Image 2).

  • Silver Gram stain showing <em>Pneumocystis jirove...

    Silver Gram stain showing Pneumocystis jiroveci.

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    Silver Gram stain showing <em>Pneumocystis jirove...

    Silver Gram stain showing Pneumocystis jiroveci.

  • Papanicolaou smear may demonstrate a foamy-appearing eosinophilic material surrounding Pneumocystis organisms (see Image 3).

  • Papanicolaou smear of <em>Pneumocystis jiroveci.<...

    Papanicolaou smear of Pneumocystis jiroveci.

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    Papanicolaou smear of <em>Pneumocystis jiroveci.<...

    Papanicolaou smear of Pneumocystis jiroveci.

Some facilities prefer to use direct immunofluorescence using monoclonal antibodies to detect Pneumocystis organisms because it may be more sensitive than histologic staining.

More on Pneumocystis (carinii) jiroveci Pneumonia

Overview: Pneumocystis (carinii) jiroveci Pneumonia
Differential Diagnoses & Workup: Pneumocystis (carinii) jiroveci Pneumonia
Treatment & Medication: Pneumocystis (carinii) jiroveci Pneumonia
Follow-up: Pneumocystis (carinii) jiroveci Pneumonia
Multimedia: Pneumocystis (carinii) jiroveci Pneumonia
References
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Further Reading

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Keywords

Pneumocystis carinii pneumonia, PCP, P carinii pneumonia, Pneumocystis jiroveci pneumonia, P jiroveci pneumonia, Pneumocystis pneumonia, PCP prophylaxis, PCP prevention, opportunistic respiratory infection, opportunistic pneumonia, HIV, AIDS

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Contributor Information and Disclosures

Author

Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Nicholas John Bennett, MB, BCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Shelley A Gilroy, MD, Clinical Professor of Medicine, State University of New York Upstate; Medical Director, Infection Control, University Hospital and Crouse Hospital, Syracuse
Shelley A Gilroy, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Frederick Burton Rose, MD, FACP, Professor, Department of Medicine, University Hospital Epidemiologist, State University of New York Upstate Medical University
Frederick Burton Rose, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Joseph C McLean, MD, Staff Physician, Department of Internal Medicine, William Beaumont Army Medical Center
Joseph C McLean, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Clinton Murray, MD, Program Director, Infectious Disease Fellowship, San Antonio Uniformed Services Health Education Consortium
Clinton Murray, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Association of Military Surgeons of the US, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Tanya S Schreibman, MD, Consulting Staff, Department of Internal Medicine, Bach and Godofsky
Disclosure: Nothing to disclose.

Michael Rigsby, MD, Director of HIV Care Program, VA Connecticut Healthcare System, West Haven Campus; Associate Professor, Department of Internal Medicine, Yale University School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Pharmacy Editor

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

Managing Editor

Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School
Harold L Manning, 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.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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