Infectious Diseases Case of the Month Case #36

An 84 y.o. white male with chronic lymphocytic leukemia (CLL) was admitted to the hospital for fever, headache, and malaise.

The patient had been diagnosed with CLL ten years previously, and his most recent chemotherapy (three months prior) had consisted of ritxuximab and bendamustine. Before that he had been treated with fludarabine.

Fevers and night sweats had been present intermittently for several weeks, and severe headache had been present for one to two weeks prior to admission. Three weeks prior to admission PCR for CMV and aspergillus galactomannan antigen assay had been negative. Headache and fever had not appeared to benefit from a course of amoxicillin/clavulanate intended for possible sinusitis. He had not had significant cough.

The patient was born and raised in Missouri but by the time of his hospitalization had been a long term resident of the Willamette Valley of Oregon. He was a retired university professor. His past medical history was notable for pulmonary tuberculosis diagnosed shortly after his World War II service in the U.S. Navy. He was treated at the time with therapeutic pneumothorax. After his diagnosis of CLL he received a course of INH for latent TB. He also had history of colectomy for diverticular disease.

At the time of admission the patient was somewhat confused. Laboratory data were notable for pancytopenia (WBC 1.7, Hgb 10.6, Plts 63). An MRI of the brain was unremarkable. A CT scan of the chest showed left sided volume lost (history of therapeutic pneumothorax) and three pulmonary nodules, the largest of which was 2.7 cm in greatest dimension (see image upper left). Results of CSF analysis included WBC 238 (87% lymphocytes), protein 133 mg/dL, glucose 61 mg/dL. CSF gram stain is pictured at lower left. The patient underwent a percutaneous biopsy of the right lung mass.

Of the choices below what the likely the cause of this illness?

       
What was the likely cause of this illness?
   
     
Diagnosis: Cryptococcus gattii
   

CSF gram stain showed narrow based budding yeast and cultures of blood, CSF, and lung biopsy all grew Cryptococcus gattii.

The patient was begun on antifungal therapy with liposomal amphotericin B and flucytosine with close attention to his pre-existing cytopenias. Serial lumbar punctures were performed to survey for and lessen moderate increased intracranial pressure. A lumbar puncture performed one week into the patient's course of therapy continued to show so many yeast that CSF WBC counts by standard methods were made inaccurate. He developed an ileus/partial bowel obstruction, suffered an aspiration pneumonia, and developed renal insufficiency (fluconazole therapy was substituted). Ultimately, given his decline and underlying disease, comfort care measures were substituted. He succumbed to his illness on the twenty-fourth hospital day.

Cryptococcus gattii has been recognized as an emerging cause of fungal disease in the Pacific Northwest. Formerly known to be a cause of human illness primarily in tropical and subtropical regions, it was first noted as a cause of veterinary disease on Vancouver Island, British Columbia in 2000, and in retrospect was discovered to have been a cause of human disease there dating to 1999. Human cases have now also been identified in the states of Washington and Oregon in the United States (enlarged map and below left). Cases of C. gattii disease are likely underreported as specialized laboratory techniques are required to distinguish gattii from neoformans species of cryptococcus.

The ecologic niche of C. gatti in the Pacfic Northwest is incompletely understood. In British Columbia, C. gattii has been isolated from surfaces of multiple tree species, soil, air, freshwater, and seawater within the Coastal Douglas Fir and Coastal Western Hemlock biogeoclimatic zones. These zones are characterized by warm, dry summers and mild, wet winters, a climate different from that traditionally associated with C. gattii. Similar climates with comparable temperature and rainfall extend further south into Washington and Oregon.

Disease due to Cryptococcus gattii may differ in some ways to that due to Cryptococcus neoformans (Case #26) though this is still being defined. C. gattii may be more apt to cause significant disease in immunocompetent individuals than C. neoformans (typically a cause of disease in HIV infected and other individuals with immunocompromise). In addition, some reports have observed variable-to-decreased in vitro antifungal drug susceptibilities for C. gattii isolates. Clinical significance of in vitro susceptibility of cryptococcal isolates is unclear, however, because testing methods are not standardized and MIC breakpoints have not been defined.

With the likely exception of Pneumocystis jirovecii all the other choices in the preceding vignette may cause central nervous system disease. Blastomyces dermatitidis (Case #15) does so uncommonly; the patient's youth in Missouri could have exposed him to this organism. Though the patient had history of infection, the CSF gram stain clearly was inconsistent with that diagnosis. is a relatively common cause of meningitis in immunocompromised individuals and certain racial/ethnic groups. Pneumocystis jirovecii is a prominent cause of pneumonitis particularly in HIV infected patients.

Ref: Datta, K. et al, Spread of Cryptococcus gattii into Pacific Northwest Region of the United States, Emerg Inf Dis, 15:8, pgs. 1185-1191, 2009


 

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