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Clinical Diagnosis of Legionnaire's Disease: Six Characteristic Clinical Predictors

      To the Editor:
      We read with interest the article by Dr Haubitz et al
      • Haubitz S.
      • Hitz F.
      • Graedel L.
      • et al.
      Ruling out Legionella in community-acquired pneumonia.
      on Dr Fiumefreddo's point score system for Legionnaire's disease in community-acquired pneumonia. Their study has merit and deserves comment.
      Because Legionnaire's disease is pneumonia with multisystem involvement, the clinical diagnosis of Legionnaire's disease remains problematic because no single clinical or laboratory finding identifies it. The difficulty with clinical predictors is in selecting parameters most indicative of Legionnaire's disease. We use 6 different characteristic clinical parameters to predict or rule out Legionnaire's disease that are readily available before Legionella serology and urinary antigen test results are reported.
      In our experience, we have found that some findings are highly characteristic of Legionnaire's disease, and their absence argues strongly against a Legionnaire's disease diagnosis.
      • Cunha B.A.
      Legionnaires disease: clinical differentiation from typical and other atypical pneumonias.
      In admitted adults with community-acquired pneumonia, we use hypophosphatemia and highly elevated erythrocyte sedimentation rate in our Legionnaire's disease criteria. If not obtained early, hypophosphatemia is easily missed and is transient. An otherwise unexplained elevated erythrocyte sedimentation rate >90 mm/h with community-acquired pneumonia occurs only with Legionnaire's disease and pneumococcal pneumonia.
      • Cunha B.A.
      • Strollo S.
      • Schoch P.
      Legionella pneumophila community-acquired pneumonia : incidence and intensity of microscopic hematuria.
      Because creatinine phosphokinase test levels are commonly elevated in Legionnaire's disease, we use this as a Legionnaire's disease predictor. On admission, otherwise unexplained microscopic hematuria is another characteristic finding of Legionnaire's disease.
      • Cunha B.A.
      • Strollo S.
      • Schoch P.
      Extremely elevated erythrocyte sedimentation rates (ESRs) in Legionnaire's disease.
      In our experience, an otherwise unexplained highly elevated ferritin level (>2 × normal) is the best single clinical nonspecific laboratory test predictor of Legionnaire's disease.
      • Cunha B.A.
      Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia.
      Clinical predictors of Legionnaire's disease should be considered only if otherwise unexplained by another disorder. No other community-acquired pneumonias are associated with highly elevated ferritin levels, microscopic hematuria, or hypophosphatemia. In our experience, community-acquired pneumonia with Legionnaire's disease is likely with >3 of these findings, whereas <3 argues strongly against Legionnaire's disease (Table).
      TableLegionnaire's Disease: Six Clinical Predictors and Diagnostic Eliminators in Adults Admitted with Pneumonia
      Pulmonary symptoms: shortness of breath, cough, and so forth with fever and a new focal/segmental infiltrate on chest x-ray.
      Diagnostic PredictorsDiagnostic Eliminators
      Clinical PredictorsClinical Eliminators
      • • Fever (>102°F)
      • • Sore throat
      • • Severe myalgias
      Laboratory Predictors
      Otherwise unexplained. If finding is due to an existing disorder, it should not be used as a clinical predictor.
      Laboratory Eliminators
      • • Highly elevated ESR (>90 mm/h) or CRP (>180 mg/L)
      • • Highly elevated ferritin levels (>2 × normal)
      • • Hypophosphatemia (on admission/early)
      • • Highly elevated CPK (>2 × normal)
      • • Leukopenia
      • • Thrombocytopenia
      • • Negative chest x-ray (no infiltrates)
      • Microscopic hematuria (on admission)
      Legionnaire's disease very likely if >3 predictors presentLegionnaire's disease very unlikely if <3 predictors or >3 diagnostic eliminators present
      CPK = creatinine phosphokinase test; CRP = C-reactive protein; ESR = erythrosedimentation rate.
      Pulmonary symptoms: shortness of breath, cough, and so forth with fever and a new focal/segmental infiltrate on chest x-ray.
      Otherwise unexplained. If finding is due to an existing disorder, it should not be used as a clinical predictor.
      We agree with Haubitz et al
      • Haubitz S.
      • Hitz F.
      • Graedel L.
      • et al.
      Ruling out Legionella in community-acquired pneumonia.
      that empiric Legionnaire's disease therapy is important if Legionnaire's disease is likely on the basis of clinical predictors. Unnecessary antibiotic coverage (eg, macrolides) promotes Streptococcus pneumoniae resistance. Unnecessary double drug therapy increases costs and potential adverse effects. Instead of double covering community-acquired pneumonia until Legionella test results are reported, it seems more prudent to use clinical predictors to treat Legionnaire's disease and atypical pathogens with doxycycline or respiratory quinolone or typical community-acquired pneumonia pathogens with a β-lactam.
      Clinical predictors can reduce unnecessary antibiotic use and minimize resistance. We commend the authors for their work and offer practitioners our 6 characteristic clinical predictors that are also highly effective in presumptively diagnosing or ruling out Legionnaire's disease.

      References

        • Haubitz S.
        • Hitz F.
        • Graedel L.
        • et al.
        Ruling out Legionella in community-acquired pneumonia.
        Am J Med. 2014; : 1010e18
        • Cunha B.A.
        Legionnaires disease: clinical differentiation from typical and other atypical pneumonias.
        Infect Dis Clin North Am. 2010; 24: 73-105
        • Cunha B.A.
        • Strollo S.
        • Schoch P.
        Legionella pneumophila community-acquired pneumonia : incidence and intensity of microscopic hematuria.
        J Infect. 2010; 61: 275-276
        • Cunha B.A.
        • Strollo S.
        • Schoch P.
        Extremely elevated erythrocyte sedimentation rates (ESRs) in Legionnaire's disease.
        Eur J Clin Microbiol Infect Dis. 2010; 29: 1567-1569
        • Cunha B.A.
        Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia.
        Clin Infect Dis. 2008; 46: 1789-1791

      Linked Article

      • Ruling Out Legionella in Community-acquired Pneumonia
        The American Journal of MedicineVol. 127Issue 10
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          Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort.
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      • The Reply
        The American Journal of MedicineVol. 128Issue 7
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          We thank Cunha et al for their interesting response and for proposing additional risk factors for early rule out of Legionella pneumonia on the basis of their experience. In the original derivation study, we evaluated different previously published predictors for Legionella, including C-reactive protein, creatinine kinase, hemoglobinuria, white blood count, and thrombocytopenia, among others.1 We used multivariate regression analysis and selected a parsimonious set of 6 predictors that showed a high discriminatory value in the initial cohort1 and in the recently published multinational validation cohort with an area under the curve of 0.91.
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