P084 Development of Creutzfeldt-Jakob disease during infliximab and ustekinumab therapy for refractory Crohn's colitis
Authors: Timothy Zaki , Vineet Rolston , Hana Yu , Susan Cohen , Lisa Malter 
Published: July 2019

BACKGROUND:
Infliximab and ustekinumab are used to treat Crohn's disease (CD). Neurologic side effects have rarely been described with either agent. We report a case of a 75-year-old female with fibromyalgia and inflammatory bowel disease with subsequent development of sporadic Creutzfeldt-Jakob disease (sCJD) after initiation of biologic therapy.

CASE:
The patient was diagnosed with ulcerative colitis (UC) in 1992 and treated with 5-ASA, 6-MP, and steroids. She stopped medication shortly thereafter but symptoms returned in November 2016 requiring hospitalization. She was treated with IV steroids, but transitioned to infliximab due to suboptimal response. In February 2017, she exhibited flushing, dizziness, and muscle spasms after an infusion. Infliximab antibody levels were >100 U/mL. Prior to transitioning therapies, a colonoscopy was performed and noted improved colitis, but biopsies showed granulomas and her diagnosis was changed to CD. A CT enterography revealed disease limited to the colon. A plan to treat the patient with ustekinumab was made in July 2017. Of note, during several office visits, the patient demonstrated hand tremor, imbalance, and widened gait she believed to have started around the time of her adverse reaction to infliximab in February 2017. The symptoms were initially thought to be related to steroid exposure, however tapering of steroids did not lead to improvement. Despite many attempts, the patient declined neurological evaluation. The symptoms worsened throughout the duration of ustekinumab therapy, and in February 2018, the patient sustained a left distal radius fracture after a fall. She agreed to a neurological evaluation in May 2018 and was found to have several focal cerebellar deficits. EEG was nonspecific. Brain MRI was notable for symmetrically increased signal within the caudate nucleus, putamen, and thalami, and prominent ventricles compatible with cerebral and cerebellar volume loss—findings suggestive of sCJD. A lumbar puncture revealed normal 14-3-3 protein in the CSF, but real-time quaking induced conversion was found to be positive. Following a goals of care discussion the patient was transitioned to home hospice.

DISCUSSION:
Trials demonstrating the efficacy of infliximab report an excellent safety profile, with rare reports of neurologic side effects. These include optic neuritis, confusion, paresthesias, and gait instability thought to be due to TNF-α blockade leading to extensive demyelination throughout the central and peripheral nervous system. Trials demonstrating the efficacy of ustekinumab also report a positive safety profile with rare neurologic side effects. We found 4 case reports of severe neurologic diseases including one case of primary progressive multiple sclerosis, amyotrophic lateral sclerosis, and 2 cases of reversible posterior leukoencephalopathy syndrome throughout treatment. These occurred in patients receiving treatment doses for either psoriasis or CD. To our knowledge, there have been no preceding case reports of sCJD development following either infliximab or ustekinumab. With respect to the onset of sCJD in our reported case, the temporal onset of symptoms succeeding the patient's infusion reaction to infliximab and commencement of ustekinumab therapy does raise the possibility of an association, however it may be a mere coincidence. Further research into the possible long-term neurologic effects of infliximab and ustekinumab is warranted.