Chest Infections NetWork Puzzler - February 28, 2010

Case Puzzler | 02.28.10

A 55-year-old man presented with fevers, cough, and confusion. He has a history of an idiopathic dilated cardiomyopathy and had a cardiac transplant 3 years ago (cytomegalovirus status is donor-negative, recipient-positive). He has had no recent episodes of rejection and no prior infectious complications.

He developed a nonproductive cough in mid-July, which worsened over 1 week. He also complained of mild headaches and loose stools. After 1 week of coughing, he became increasingly confused, and had altered speech over the past 24 hours. His wife found him difficult to arouse and called emergency medical services.

He lives in a suburban area with his wife and adult daughter. He has not traveled internationally, has no history of TB, and has not been in contact with anyone who is sick. He is a disabled truck driver.

He had been on stable immunosuppressive therapy, including tacrolimus, 2 mg po twice daily; mycophenalate, 500 mg po qd; prednisone 12.5 mg po qd; and acyclovir orally. He was taken off sulfamethoxazole and trimethoprim.

On admission, temperature = 100.3°F, pulse = 68/min, and blood pressure = 98/56 (baseline). So₂ was 87% on room air. He was disoriented, with a depressed level of consciousness. Results were negative for the head and neck exam, with no nuchal rigidity. His lungs had extensive crackles in the right upper field and throughout the left lung. His cardiac examination was unremarkable, and his neurologic examination was limited but seemed to be nonfocal. The patient would frequently wave his hands in the air.

The following laboratories were remarkable: WBC = 2.8 x 10⁹/L(baseline 7 x 10⁹ /L- 10 x 10⁹/L), Hemoglobin = 11 g/dL. Comprehsive metabolic panel showed alanine Aminotransferase = 110 U/L; otherwise normal results.

Figure 1. Chest radiograph.

The patient was started on IV vancomycin, ceftriaxone, azithromycin, and acyclovir. Lumbar puncture showed 22 WBC/mm³(23% neutrophils, 70% lymphocytes) and 3 RBC/mm³. Cerebrospinal fluid (CSF) glucose was within normal limits and CSF protein level was elevated at 74 mg/dL. Gram stain of CSF showed no organisms, and the cryptococcal antigen screen was negative. The CSF was sent for numerous molecular tests, including herpes simplex virus and cytomegalovirus polymerase chain reaction (PCR) assays.

Results of the MRI and magnetic resonance angiogram scan of the brain with contrast were normal. Bronchoscopy showed inflamed airways and moderate secretions. Gram stain showed no organisms and many polymorphonuclear cells. Results of routine cultures were negative.

The patient improved when receiving broad spectrum antibiotics. Results of bronchoalveolar lavage (BAL) fluid stains and cultures were negative for the following: pneumocystis stain, Nocardia stain and culture, Legionella direct fluorescent antibody test, respiratory viral panel, and acid-fast bacilli, fungi, herpes simplex virus, and cytomegalovirus tests.

Results of CSF molecular studies were later negative, including PCR assay for herpes simplex virus.

The patient had a slow recovery but eventually was discharged to home receiving antibiotics. A certain diagnosis was suspected, which was later confirmed.

See the Answer

Encephalitis, secondary to Legionella infection

Discussion

Cultures from the BAL fluid were later positive for Legionella micdadei. The patient was diagnosed with encephalitis secondary to legionella infection and continued receiving macrolide therapy.

This case illustrates the differential diagnosis of pneumonia with encephalitis. The patient’s clinical presentation was remarkable for a frank encephalitis with only mild inflammation in the CSF and normal brain imaging results. Recent guidelines issued by the Infectious Diseases Society of America outline the approach to patients with encephalitis, including those with accompanying respiratory symptoms. Diagnostic considerations include mycoplasma infection (although this is somewhat controversial), histoplasmosis, Q fever, influenza, and TB. In addition, Legionnaires disease has been described with prominent CNS involvement, and this was the tentative diagnosis in the case. This is an unusual complication of Legionnaires disease, but a variety of CNS manifestations have been described, including brain stem lesions, reversible corpus callosum lesions, cerebellar dysfunction, and global encephalitis.

In the immunocompromised host, the differential diagnosis of pulmonary infiltrates with encephalitis includes all of the above-mentioned infections, along with Cryptococcus neoformans, which can cause both meningitis and/or encephalitis, cytomegalovirus, Nocardia sp, and others. It should be noted that the differential diagnosis in our case is one of pulmonary infiltrates with encehalitis rather than meningitis, which has a somewhat different set of diagnostic considerations.

In our case, encephalitis from Legionella was strongly suspected despite the initial negative result for the Legionella pneumophila direct fluorescent antibody test and urinary antigen test. Most commercially available rapid systems detect L pneumophila but not other Legionella species from both respiratory specimens and urinary specimens. The L micdadei was only detected after extended incubation on enriched agar.

L micdadei is the second most common cause of Legionnaires disease. It is a pathogen that generally infects immunocompromised hosts but can cause a respiratory syndrome indistinguishable from L pneumophila in healthy hosts. Our patient made a full recovery with treatment with a macrolide.

About 1 year later, the patient relapsed with a second episode of L micdadei pneumonia and severe encephalitis, in an almost identical presentation.

Chest Infections NetWork Puzzler - February 28, 2010

Recommended Reading

Case Puzzlers