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A 65-Year-Old Groundskeeper With High Fever, Pulmonary Nodules, and Thoracic Lymphadenopathy FREE TO VIEW

Clayton L. Foster, MD; Jessica Badlam, MD; Mary Ann De Groote, MD; Edward D. Chan, MD
Author and Funding Information

CORRESPONDENCE TO: Edward D. Chan, MD, D509, Neustadt Building, National Jewish Health, 1400 Jackson St, Denver, CO 80206


Copyright 2016, . All Rights Reserved.


Chest. 2016;149(6):e191-e194. doi:10.1016/j.chest.2015.12.035
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Published online

A 65-year-old man with treated latent tuberculous infection presented with 1 week of fevers (up to 39.6°C), chills, headache, lightheadedness, and malaise. He reported a chronic, nonproductive cough without hemoptysis but denied other localizing symptoms, sick contacts, or recent travel. He lived in an urban area in eastern Colorado and owned one healthy dog but otherwise denied known animal exposures. He was a retired oil driller who had worked in southern Arizona, New Mexico, and northern Mexico (Sonora region). Other travel included 3 years in the early 1970s working as a military aircraft mechanic in Vietnam, Laos, and Thailand. Six weeks prior to admission, he began work as a groundskeeper on a golf course that had experienced recent flooding, using a riding mower and exposing himself to airborne dust and organic debris. He smoked a pipe daily for 30 years but quit 2 months prior to presentation, although he continued to smoke marijuana weekly. He denied intravenous drug use.

Figures in this Article

On examination, his temperature was 38.7°C; pulse, 74 beats/min; respiratory rate, 16 breaths/min; and blood pressure, 113/79 mm Hg. Examination revealed a diaphoretic, ill-appearing man with otherwise unremarkable findings.

The complete blood count was notable for a white blood cell count of 13,300/μL, with 77% neutrophils, 2% bands, 10% lymphocytes, and 11% monocytes. The serum sodium level was 131 mM, but other electrolytes and kidney and liver function test results were all within normal limits. A CT scan of the chest showed multiple bilateral pulmonary nodules with lower lung predominance (Fig 1A), as well as bilateral mediastinal and hilar lymphadenopathy (Fig 1B).

Figure 1
Figure Jump LinkFigure 1 Chest CT scans. A, Axial chest CT image on admission shows bilateral nodular opacities in the lower lobes. B, Mediastinal window of the admission chest CT scan with contrast shows prominent right hilar (arrowheads) and modest mediastinal (arrow) lymphadenopathy. Less extensive hilar lymphadenopathy (not visible in current image) was also present on the left. C, Mediastinal window of a chest CT scan on hospital day 6 revealed a new, small pleural effusion on the left, with unchanged lymphadenopathy and, also, worsening of the bilateral nodular opacities (not seen in this image).Grahic Jump Location

What is the diagnosis?

Diagnosis: Typhoidal tularemia with secondary pulmonary involvement

Francisella tularensis, a small, gram-negative aerobic coccobacillus, causes a spectrum of diseases known as tularemia. It is fastidious and typically requires cysteine or cystine for growth. While the bacterium can grow on chocolate agar, modified Thayer-Martin medium, and buffered charcoal-yeast extract agar, it is slow-growing and rarely isolated from clinical specimens. It is estimated that only 10 to 50 organisms are required to produce disease by the intradermal or inhalational route. Thus, F tularensis is a category A (high-priority) bioterrorism agent, and, if suspected in a cultured specimen, biosafety level 3 precautions must be observed. Hospital laboratories and the public health department should always be notified of possible diagnoses of tularemia. Acute- and convalescent-phase serologic testing, or polymerase chain reaction testing, of tissue samples can confirm the diagnosis when cultures are negative.

F tularensis is endemic throughout the Northern Hemisphere, although prevalence varies by country. Three subtypes cause the majority of disease: Subspecies tularensis type A1 occurs primarily in the central United States; tularensis type A2 occurs in the western United States; and subspecies holarctica (type B) is dispersed throughout the Northern Hemisphere. Lagomorphs (rabbits and hares) and rodents are the primary reservoir (including squirrels in urban areas), although arthropods such as ticks and deer flies can harbor the bacterium. Transmission to humans occurs primarily by direct contact with a contaminated animal, a bite from an infected arthropod, or inhalation of aerosolized bacteria. Tularemia has six major clinical forms: ulceroglandular, glandular, oculoglandular, pharyngeal, pneumonic, and typhoidal. The first three present with regional lymphadenopathy from intradermal inoculation (with or without an ulcerative skin lesion) or inoculation of the eye (resulting in severe conjunctivitis). Pharyngeal tularemia occurs with ingestion of contaminated food or water, causing severe, ulcerative pharyngitis. Primary pneumonic tularemia is acquired by inhalation of organisms, although pneumonic disease can also be secondary to hematogenous spread with any form of the disease. Last, typhoidal tularemia is characterized by a nonspecific febrile illness not fitting the aforementioned forms of disease, although up to 45% of patients will have lung opacities. Characteristic parenchymal abnormalities include bilateral lower zone patchy opacities, denser lobar consolidation, or a diffuse miliary pattern. Despite its virulence, human-to-human transmission of F tularensis has not been observed, and no special patient isolation precautions are required.

With its protean manifestations, the diagnosis of tularemia warrants consideration in the appropriate setting. Patients with pneumonic tularemia are less likely to recall a potential source of exposure than those with other forms of disease, but they are more likely to require hospitalization and die of their illness. Radiographic findings can include lobar, peribronchial, nodular, miliary, or, less commonly, rounded opacities. Indeed, initial suspicion for primary bronchogenic carcinoma or metastatic disease has been reported. Cavitation of pulmonary lesions occurs infrequently. Hilar lymphadenopathy has been described in 30% to 45% of patients with pneumonic tularemia. The prevalence of pleural effusions in pneumonic tularemia varies widely, from 20% to 80%. Pleural fluid is typically exudative and lymphocytic but can have many neutrophils, as well as high-level lactate dehydrogenase, glucose in the normal range, and elevated adenosine deaminase—features that overlap with tuberculosis. In North America, empiric treatment for tularemia is recommended for community-acquired pneumonia with thoracic lymphadenopathy and/or at-risk exposure history. Clinical outcomes vary widely from self-limiting illness with minor radiographic abnormalities but no symptoms of pneumonia to mortality rates of 60% with untreated primary pneumonic tularemia. This range of outcomes may be due in part to the various subtypes of F tularensis, as mortality rates among patients with A1 infection are consistently higher than with other types.

There are no prospective, randomized controlled trials examining antibiotic efficacy in the treatment of tularemia. Streptomycin or gentamicin is considered the first-line treatment, although with meningitis, chloramphenicol or doxycycline may be added for optimal penetration into the subarachnoid space. For milder disease, oral ciprofloxacin or doxycycline is effective, although fluoroquinolones are associated with lower rates of relapse. While many β-lactams are effective in vitro, their clinical use yields unacceptably high rates of treatment failure. Optimal treatment duration is unclear, but suggested regimens range from 7 days with aminoglycoside monotherapy and good clinical response to 21 days with tularemic meningitis or initial clinical failure.

Clinical Course

The patient received 7 days of ceftriaxone and azithromycin for presumed community-acquired pneumonia, but fever and malaise persisted. A transesophageal echocardiogram revealed no vegetations, and multiple blood culture results were negative. A sputum culture was not processed because of oropharyngeal contamination. A repeat CT scan of the chest on hospital day 6 showed unchanged lymphadenopathy, an increase in size of the pulmonary nodules, and a new left pleural effusion (Fig 1C), which was not sampled because of its small size. He was given oral moxifloxacin monotherapy for several days, and his fever subsided. However, he was discharged on hospital day 9 without antibiotics since the leading diagnostic consideration at that time was a noninfectious but yet-to-be-identified process. Although his occupational history of mowing lawns, obtained on hospital day 6, prompted collection of serum to determine F tularensis antibody titers, he was not given a full course of empiric treatment for tularemia. In retrospect, he should have received empiric tularemia treatment on admission in light of his community-acquired pneumonia with hilar lymphadenopathy in an endemic region. His defervescence with a brief course of moxifloxacin was an additional missed clue to the diagnosis. Five days after discharge, F tularensis IgM test results indicated 42 units/mL (cutoff for positivity, 16 units/mL). His fever and malaise returned, and he was prescribed 3 weeks of ciprofloxacin as an outpatient. Repeat serologic testing 3 weeks after initial presentation showed an increase in F tularensis IgM to 68 units/mL. Symptoms rapidly resolved on administration of ciprofloxacin, and follow-up imaging 6 weeks after admission showed resolution of pleural fluid and lymphadenopathy with a significant decrease in the size of all pulmonary nodules.

  • 1.

    There are six major clinical forms of tularemia: ulceroglandular, glandular, oculoglandular, pharyngeal, pneumonic, and typhoidal. The chest radiographic manifestations of pneumonic and typhoidal tularemia include bilateral patchy opacities, dense lobar consolidation, and a miliary pattern as well as thoracic lymphadenopathy and pleural effusions.

  • 2.

    F tularensis is endemic throughout the Northern Hemisphere, but the most severe disease is produced by type A1 in the central United States. Transmission to humans occurs primarily by direct contact with a contaminated animal, a bite from an infected arthropod, or inhalation of aerosolized bacteria. Interestingly, landscaping activities such as mowing lawns—this patient’s occupation—are considered to be risk factors for pneumonic tularemia.

  • 3.

    Patients with tularemic pneumonia are less likely to recall a specific source of exposure, but they tend to have higher morbidity and mortality compared with patients with other forms of the disease.

  • 4.

    Given the widespread endemicity of F tularensis in North America, tularemia should be considered in the differential diagnosis of community-acquired pneumonia in someone with at-risk recreational or occupational exposure and/or the presence of hilar lymphadenopathy. In this setting, empiric treatment with an aminoglycoside is warranted for moderate to severe disease and oral ciprofloxacin or doxycycline for mild disease.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 Chest CT scans. A, Axial chest CT image on admission shows bilateral nodular opacities in the lower lobes. B, Mediastinal window of the admission chest CT scan with contrast shows prominent right hilar (arrowheads) and modest mediastinal (arrow) lymphadenopathy. Less extensive hilar lymphadenopathy (not visible in current image) was also present on the left. C, Mediastinal window of a chest CT scan on hospital day 6 revealed a new, small pleural effusion on the left, with unchanged lymphadenopathy and, also, worsening of the bilateral nodular opacities (not seen in this image).Grahic Jump Location

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