Disseminated Cryptococcal Infection in a Patient on Ruxolitinib

1University of Michigan Health System, Ann Arbor, MI

Meeting: Hospital Medicine 2015, March 29-April 1, National Harbor, Md.

Abstract number: 514

Keywords:

Case Presentation:

A 74 year old male with a history of cerebral vascular disease as well essential thrombocythemia that had progressed to myelofibrosis maintained on ruloxitinib for 13 months presented with four months of intermittent somnolence, confusion and failure to thrive.  His symptoms were first noted during a hospitalization for health care associated pneumonia and initially attributed to delirium. 

            On admission, he was occasionally responsive to verbal stimuli and always responsive to tactile and painful stimuli. His vital signs were normal and he was afebrile.  His neurologic exam was notable for mild bilateral cogwheel rigidity in his upper extremities, but was otherwise non-focal without meningeal signs.  His initial labs showed an elevated WBC count of 11.4 with 80% neutrophils without immature granulocytes and 6% peripheral blasts. Complete metabolic panel was within normal limits and blood cultures showed no growth.  Non-contrast head CT on admission was consistent with prior ischemic events. 

            On day 2, the patient became unresponsiveness for three minutes. He did not respond to verbal, tactile or painful stimuli and he appeared to have right-sided neglect.  A non-contrast head CT showed no acute changes.  His symptoms resolved spontaneously over the course of hours.   An EEG was negative for subclinical seizures and a lumbar puncture was performed.

            CSF studies were remarkable for an elevated protein(79 mg/dL), low glucose(34 mg/dL) and 75 WBC/cmm with differential showing 46% neutrophils, 4% lymphocytes, 11% histiocytes, and 2% blasts. Initial gram stain showed no bacterial organisms, but did note yeast.  Cryptococcal antigen testing was performed and was found to be present both in the cerebrospinal fluid(titer 1:640) and peripheral blood(titer 1:2560.) Fungal culture was performed on the CSF and blood cultures were obtained which both grew Cryptococcus neoformans.  The patient was started on amphotericin and flucytosine with frequent large volume lumbar punctures with significant improvement in mental status.  

Discussion:

Our patient presented with disseminated Cryptococcus neoformans infection while treated with ruxolitinib, a JAK1&2 inhibitor, for the treatment of myelofibrosis with no other underlying immune-compromising conditions.  Numerous case reports have reported opportunisitic infections arising while on ruxolitinib (2,3,4,5). 

Conclusions:

With an increasing number of cases being reported clinicians should remain aware of the possibility of immunosuppression and atypical infections in association with ruxolitnib use.

  1. Levine RL, Wadleigh M, Gilliland DG. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7(4):387-397
  2. Wysham, NG, Sullivan DR, Allada G. An Opportunistic Infection associated with Ruxolitinib a Novel Janus Kinase 1,2 Inhibitor. Chest 2013; 143(5):1478-1479
  3. Lee SC, Feenstra J, Georghiou PR. Pneumocysitis jiroveci pneumonitis complicating ruxolitinib therapy. BMJ Case Rep Publisehd Online: 2014 doi 1.1136/bcr-2014-204950.
  4. Caocci G,  Murgia F, Podda L, La Nasa G. Reactivation of Hepatitis B virus Infection Following Ruxolitinib Treatment in a Patient With Myelofirbrosis. Leukemia (2014) 28, 225–227; doi:10.1038/leu.2013.235.
  5. Goldberg, RA, Reichel E, Oshry LJ. Bilateral Toxoplasmosis Retinitis Associated with Ruxolitinib. N Engl J Med 369;7:681-683.

To cite this abstract:

Sakr F, Greenberg J, McQuillan M. Disseminated Cryptococcal Infection in a Patient on Ruxolitinib. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 514. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/disseminated-cryptococcal-infection-in-a-patient-on-ruxolitinib/. Accessed November 22, 2019.

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