Case report: A 30-year-old man underwent small bowel transplantation for severe short bowel syndrome (SBS) in December 2010. He had no history of hypertension and diabetes mellitus. Serum anti-virus IgG and IgM examinations for CMV, RU, HSV, TOX, EB and COX were all negative before the transplantation surgery. He was given corticosteroid-tacromilus (FK506)-mycophenolate mofetil (MMF) treatment to suppress rejection. High-dose Methylprednisolone (400mg/day for 1 day and 200mg/day for 2 days) was given in the first three days after transplantation, than change to oral prednisone 20mg/day and reduced to 10mg/day after 1 week. MMF started from 1gtwo times per day since the first day after surgery and the dose was slowly reduced and stopped in about 2 months because of the bone marrow suppression. The patient was receiving FK506 since the first day after surgery. The starting dose was 2mg three times per day and the drug concentration in blood was monitoring. The dose of FK506 was changed according to the drug concentration and the graft immunological rejection status which was investigated by enteroscopy and biopsy. At the second month after transplantation, the patient began to have abnormal renal function. Dosage of FK506 was controlled to balance the acute rejection treatment and nephrotoxity. In the first three months after the transplantation, the blood drug concentration of FK506 fluctuated from 3.7ng/ml to 16.6ng/ml and the average level was around 10ng/ml.
Three months after the transplantation, the patient complained for the decreased vision. At the day before the ocular defect, the drug concentration reached 13.9ng/ml. Ophthalmological examinations than were practiced for him. The visual acuity was HM/BE bilaterally. Pupil reactions to light were slowly and weak in both eye and there was no relative afferent papillary defect detected. Introcular pressure and anterior segment slit-lamp exam were normal. In fundus examination, swollen optic disks with blurred edge and pre-retinal hemorrhage beside the optic disks were detected in both eyes (figure1a). Fluorescein angiography demonstrated that delayed filling of fluorescein in the optic disc in both eyes, from early phase to artery-venous phase (figure 1b). The patient was too weak to finish the perimetry and visual electrophysiology exams. MRI of head was normal. Diagnose was given as bilateral anterior ischemic optic neuropathy and neurotoxicity of calcineurin inhibitors FK506 was suspected. Topical compound anisodine hydrobromide injection was applied as vasodilator, Mecobalamin and Vit B1 was given as neuroprotective agent. The enteroscopy and biopsy of the graft still showed an acute rejection condition. The FK506 was a very effective immunosuppressive agent. The surgery department decided to use FK506 continuously but reduce the dose to 2mg two times per day. Three weeks after the treatment changes, the drug concentration of FK506 reduced to 8ng/ml and the visual acuity of the patient improved to 4/200 inright eye and 2/200 inleft eye. Both optic discs had a clear edge but their colors were pallor and the left one was nearly white. The hemorrhages had been resolved. The patient had got optic atrophy in both eyes. Although the surgery continuously reduced the dose of FK506 to 1mg three times per day, the visual acuity had no future improvement.
Five months after the transplantation, the patient complained for severe headache and vision loss. Ten minutes after that, he had a sudden-onset generalized tonic seizure with impairment of consciousness. Blood pressure was 167/100mmHg and heart beat was 140bpm. He then had repetitive onset 3 times in 2 hours. Dexamethasone, luminal, mannitol, Furosemide and Clonazepam were used for emergency rescue.Cranial CTand MRI were practiced. MRI demonstrated abnormal hyperintensities in the cortex and subcortex of occipital lobe bilaterally (figure2a). 2 hours and 20 minutes after the first onset, the patient stopped seizure and kept in coma condition for two days until came back to clear at the third day after seizure onset. Suspecting for the neurotoxity of FK506, surgery department further decreased FK506 to 1mg three times per day and combined used rapamycin for immunosupression. At the same time, the dose of prednisone was elevated to 20mg per day. At the sixth day after seizure, drug concentration of FK506 was down to 1.6ng/ml and repeated cranial MRI revealed a smaller lesion with decreased signal intense at the same region (figure 2b). The visual acuity was counting fingers before the eye bilaterally. Both optic disks were atrophic. After that, the drug concentrations were controlled around 5-7ng/ml, the visual acuity had no serious deterioration. |
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