eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Legionnaires Disease: Differential Diagnoses & Workup

Author: 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
Coauthor(s): Lynn E Sullivan, MD, Assistant Professor of Medicine, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Feb 5, 2008

Differential Diagnoses

Other Problems to Be Considered

Typical CAPs
Atypical CAPs
Severe CAP

Patients diagnosed with Legionella pneumonia are not co-infected with other organisms (eg, pneumococcal species). The differential diagnoses include other atypical pathogens (eg, Mycoplasma, psittacosis), Chlamydophila pneumoniae, tularemia, and Coxiella burnetii. L pneumophila bacterium represents a definite pathogen; therefore, its isolation always indicates infection.

Workup

Laboratory Studies

  • While pneumonias caused by numerous pathogens share similar laboratory findings, hyponatremia (sodium <130 mEq/L) secondary to the syndrome of inappropriate antidiuretic hormone is more common in legionnaires disease (LD) than in pneumonias secondary to other pathogens; however, this is not specific for LD.
  • Additional laboratory findings in LD and in pneumonias due to other causes include the following:
    • Elevated liver enzyme levels
    • Increased creatine phosphokinase levels
    • Increased creatine phosphokinase (CPK) levels
    • Increased C-reactive protein levels (>30 mg/L)
    • Hypophosphatemia (specific to LD excluding other causes of hypophosphatemia)4
    • Microscopic hematuria
    • Proteinuria (40%)
  • Gram stain
    • Typically, many leukocytes and a paucity of organisms are observed.
    • If visible, the organisms are small, faintly staining, gram-negative bacilli.
  • Culture of respiratory secretions
    • The definitive method for diagnosing Legionella is isolation of the organism in the respiratory secretions (ie, sputum, lung fluid, pleural fluid). However, Legionella species do not grow on standard microbiologic media.
    • Legionella requires buffered CYE agar and cysteine for growth. Optimal growth occurs at 35-37°C.
    • Legionella is a slow-growing organism and can take 3-5 days to produce visible colonies. The organisms typically have a ground-glass appearance.
    • Routine sputum cultures have a sensitivity and specificity of 80% and 100%, respectively.
    • Transtracheal aspiration of secretions or bronchoscopy specimen increases the sensitivity.
    • Bronchoalveolar lavage (BAL) fluid provides a higher yield than bronchial wash specimens.
  • Blood cultures: Legionella can be isolated from blood, but it shows a much lower sensitivity.
  • Direct fluorescent antibody staining of sputum
    • Direct fluorescent antibody staining (DFA) is a rapid test that yields results in 2-4 hours but has a lower sensitivity. The specificity of DFA is 96-99% using monoclonal antibody instead of polyclonal antibody.
    • A positive result depends on finding large numbers of organisms in the specimen; therefore, the sensitivity is increased when samples from the lower respiratory tract are used.
    • DFA results rapidly become negative (in 4-6 d).
  • Serology
    • The most widely used tests include the immunofluorescent antibody (IFA) and enzyme-linked immunosorbent assay (ELISA). A single increased antibody titer confirms LD if the IFA titer is greater than or equal to 1:256.
    • While LD serologic tests are the most readily available, they require a 4-fold increase in antibody titer to 1:128 or greater, which takes 4-8 weeks. Paired measurements from both the acute and convalescent periods should be obtained, since an antibody response may not be apparent for up to 3 months. Of note, antibody levels do not increase in approximately one third of patients with LD.
  • Urinary antigen test
    • The Legionella lipopolysaccharide antigen is detected with ELISA, radioimmunoassay (RIA), and the latex agglutination test. The Legionella lipopolysaccharide antigen becomes detectable in 80% of patients on days 1-3 of clinical illness.
    • The urinary antigen assay can be used to detect only L pneumophila (serogroup 1).5
    • The advantages of this test include rapidity and simplicity. In addition, the relative ease of obtaining a urine sample compared with obtaining sputum specimens and the persistence of antigen secretion in patients who are on antibiotic therapy increase the usefulness of the urine antigen detection method.5
    • The urinary antigen result can remain positive for months after the acute episode has resolved.5
  • Amplification with polymerase chain reaction
    • Polymerase chain reaction (PCR) of urine, serum, and bronchiolar lavage fluid is very specific for the detection of legionellae, but the sensitivity is not greater than that of culture.
    • The primary benefit of this procedure, like IFA titers, is that it can be used to detect infections caused by legionellae other than L pneumophila serogroup 1.6

Imaging Studies

  • No typical LD radiographic presentation exists.7
  • Rapidly progressive asymmetrical infiltrates are characteristic of LD.
  • Approximately one quarter of patients had infiltrates that were described as interstitial. Almost half of the patients had patchy alveolar infiltrates.
  • In general, the abnormalities are typically unilateral and are found in the lower lobes.
  • Pleural effusions are found in one third of patients.
  • Cavity and abscess formation are rare and can occur in immunocompromised hosts.
  • Improvement revealed on the chest radiograph can lag behind the clinical improvement by 5-7 days. The abnormalities on chest radiograph can take up to 3-4 months to resolve completely.

Procedures

  • Bronchoscopy: While the sensitivity of specimens retrieved via bronchoscopy is comparable to that of sputum, BAL fluid gives a higher yield than bronchial wash specimens.
  • Thoracentesis: If a pleural effusion is present, fluid can be evaluated using DFA or LD culture.

Histologic Findings

Typically, legionellae histopathological lesions are found in interstitial lining and alveoli with polymorphonuclear cells and macrophages.

More on Legionnaires Disease

Overview: Legionnaires Disease
Differential Diagnoses & Workup: Legionnaires Disease
Treatment & Medication: Legionnaires Disease
Follow-up: Legionnaires Disease
References
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References

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Further Reading

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Keywords

legionnaire disease, LD, Legionella pneumonia, Legionella pneumophila, L pneumophila, legionellosis, legionnaires disease, Pontiac fever, nosocomial pneumonia, community-acquired pneumonia, Legionella micdadei, L micdadei, Legionella bozemanii, L bozemanii, Legionella dumoffii, L dumoffii, Legionella longbeachae, L longbeachae, Pittsburgh pneumonia agent

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Contributor Information and Disclosures

Author

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.

Coauthor(s)

Lynn E Sullivan, MD, Assistant Professor of Medicine, Yale University School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Fred A Lopez, MD, Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine
Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

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

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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