Tacrolimus

Abstract

Optic neuropathy, acute kidney injury and posterior reversible encephalopathy syndrome: 3 case reports In a case series, involving 2 women and a man aged 23–65 years were described, who developed optic neuropathy, acute kidney injury or posterior reversible encephalopathy syndrome during immunosuppressant treatment with tacrolimus [time to reactions onsets and routes not stated; not all outcomes stated] Case 1: A 33-year-old woman developed optic neuropathy during immunosuppressant treatment with tacrolimus. The woman presented to the neurology department with complaints of non-specific headache, vision loss (blurriness, darkness, loss of peripheral vision), weakness and lethargy. Her past medical history was significant for diabetes and cystic fibrosis. She underwent double lung transplantation 11 years prior to the presentation. She had been receiving immunosuppressant treatment with tacrolimus 0.5 mg/day. Several prior admissions for headache, neck pain and subjective fever were also noted. Previous MRI also revealed new T2/flair abnormalities along the optic chiasm and proximal optic tracks, hypothalamus and cerebellum. On the basis of above findings tacrolimus was discontinued although tacrolimus levels remained within therapeutic range (5-20 ng/mL). Acute kidney injury of 2.51 was also noted at that time. On presentation at another institution three months later, she reported continued worsening of her visual symptoms over the course of 2 to 3 months. On examination, visual acuity was found to be 20/300 in the right eye and 20/200 in the left eye. Hardy-RandRittler color plates (0/12 in both the eyes) revealed severe dyschromatopsia. A 24-2 visual field demonstrated poor reliability, but suggested bitemporal field loss with significant field constriction. Dilated fundus examination revealed optic nerve pallor and atrophy. Optical coherence tomography confirmed diffuse ganglion cell layer loss. At this admission superficial cellulitis of the hand was noted, which was treated with vancomycin. However, broader infectious examination was unremarkable. Kidney function also improved with respect to previous admission. Repeat brain, orbit and spinal MRI showed unchanged MRI abnormalities, with persistent hyperintensity of the optic chiasm. Her visual symptoms continued even after treatment for cellulitis along with neuroradiologic findings. Therefore, tacrolimus-induced optic neuropathy was diagnosed. Case 2: A 65-year-old man developed optic neuropathy during immunosuppressant treatment with tacrolimus. The man, who had history of idiopathic pulmonary fibrosis complicated by pulmonary hypertension underwent single left lung transplantation 2 years prior to the admission. His post-transplant course was complicated by cryptococcal meningitis, which resolved after treatment. He had been receiving immunosuppressive treatment with tacrolimus at an alternating dose of 0.5mg and 0.25mg twice daily along with prednisone and mycophenolate-mofetil [cellcept]. On admission, he presented with acute changes in mental status and slurring of speech. Varicella zoster virus infection in the trigeminal V1 distribution was suspected. At that time, he also complained of blurry vision in the left eye. On ophthalmology consultation, vision was found to be 20/50 in both the eyes without any other significant changes except tilted optic discs, which was a benign finding. Later, varicella zoster virus infection was noted, and treated with aciclovir [acyclovir]. Mild acute kidney injury was also noted. Subsequently, his condition improved and returned to baseline. One month later, he was again examined for worsening of the vision in the right eye. On evaluation, decrease in right eye vision from 20/50 to 20/70 was noted. A novel right afferent pupilary defect and new temporal vision deficit was also noted. Optic nerve examination revealed pallor in both the eyes, consistent with subacute to chronic process. Ishihara colour plates revealed decrease in colour vision (1.5/14 in the right eye and 11.5/14 in the left eye). Optic coherence tomography revealed diffuse asymmetric nerve fiber loss, which was greater in right eye then left eye, consistent with optic nerve atrophy. MRI was free from any leptomeningial spread. His kidney function normalised and he was on treatment with aciclovir. On the basis of above findings, tacrolimus-induced optic-neuropathy was diagnosed. The man stopped receiving tacrolimus. Case 3: A 23-year-old woman developed acute kidney injury, posterior reversible encephalopathy syndrome and optic neuropathy during immunosuppressant treatment with tacrolimus. The woman, who had cystic fibrosis, underwent bilateral lung transplantation, one year prior to the admission. She was transferred to the ICU due to respiratory failure. Prior to the admission he had been receiving tacrolimus 0.5mg daily along with prednisone. At the time of admission, she was intubated for acute respiratory distress. On evaluation, acute cellular rejection was diagnosed, and tacrolimus level rose from 17 ng/mL to 53 ng/mL. Tacrolimus was held. A previous admission was also noted one year ago due to tacrolimus-induced acute kidney injury, which had resolved. At current presentation, creatinine was found to be 2.37, which was consistent with acute kidney injury. She was treated with unspecified pulse dose steroids, IV immune-globulin [immunoglobulin], plasma exchange and antithymocyte globulin [thymoglobulin]. Clinical improvement was noted. Five days later, she was extubated. At one month, she reported a new right temporal visual field deficit. On examination, her vision was found to be 20/20 in both the eyes. Visual field was found to be full. Dilated examination revealed temporal nerve pallor in the right eye and diffuse optic atrophy in the left eye. Optical coherence tomography revealed asymmetric nerve loss greater in left eye then right eye which was consistent with tacrolimus-induced optic neuropathy. Wider visual field test was scheduled. However, she was admitted to the neuro-intensive care unit due to bifrontal seizures and altered mental status. Brain MRI revealed changes which were consistent with posterior reversible encephalopathy syndrome. Tacrolimus treatment was stopped, which led to improvement in her symptoms and brain lesions. However, she remained in hospital for a month due to redevelopment of acute cellular rejection, which required further medication management.