A 66-year-old woman with a 5-year history of rheumatoid arthritis was admitted with mental obtundation. Six hours before admission, headache with fever developed. She had been given 40 mg of adalimumab every other week for 22 months prior to presentation, in addition to prednisolone (10 mg/d) and methotrexate (17.5 mg/wk). Urosepsis from a renal abscess due to Enterobacter aerogenas had occurred 4 months earlier. As a result, adalimumab, which inhibits TNF-α, a component of the immune system that protects the body from infection, and methotrexate as an immunosuppressant, had been stopped to control the infection. The urosepsis had improved but her symptoms of arthritis became aggravated. So, about 6 weeks before admission, adalimumab therapy was restarted. Her clinical symptoms of rheumatoid arthritis had improved, but 1 week before admission, small erythematous papules had developed on her left gluteal region. On admission, these skin lesions were positive for the Tzanck test. On presentation, her mental state was confusional, without focal neurological deficits. Body temperature was 39°C, and there was neck stiffness and Kernig signs. No papilledema was observed. At that time, cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis (150 cells/mm3, 72% lymphocytes), a red blood cell count of 3810 cells/mm3, a glucose level of 60 mg/dL (serum glucose level, 127 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), and a protein level of 330 mg/dL. Serum biochemistry findings, urine analysis results, and chest radiograph were all normal. Brain magnetic resonance imaging, performed at admission, indicated multifocal parenchymal lesions and hemorrhage in the brainstem and supratentorial areas (Figure 1). Based on these findings, acyclovir (10 mg/kg every 8 hours) and empirical broad-spectrum antibiotics (piperacillin/tazobactam) were given immediately, and adalimumab and prednisolone were stopped. The CSF polymerase chain reaction test results were initially negative for herpes simplex viruses 1 and 2, VZV, cytomegalovirus, Epstein-Barr virus, and mycobacterium tuberculosis. The patient's neurological status continued to deteriorate to stuporous mentation, and both eyeballs started to deviate downward, with sluggish light and corneal reflexes. On the fifth day, follow-up brain magnetic resonance imaging demonstrated worsening of the multiple bilateral parenchymal involvement, with multifocal hemorrhage and hydrocephalus in addition to the preexisting lesions (Figure 2). The CSF analysis revealed aggravated pleocytosis (1130 cells/mm3, 47% lymphocytes), a red blood cell count of 12 120 cells/mm3, a glucose level of 171 mg/dL (serum glucose level, 255 mg/dL), and a protein level of 290 mg/dL. The second CSF polymerase chain reaction test results were positive for VZV but negative for herpes simplex viruses 1 and 2, Epstein-Barr virus, cytomegalovirus, and mycobacterium tuberculosis. At that time, CSF test results were positive for anti-VZV IgM antibody. Despite intensive antiviral medication, the patient's clinical status deteriorated, with serious neurological deficits. Although VZV was detected in her CSF, antibacterial agents were continued because of newly developed pneumonia. The patient died of VZV multifocal vasculopathy and sepsis, possibly aggravated by coinfection with Klebsiella pneumonia, on the 13th day.