Everolimus-Induced Posterior Reversible Encephalopathy Syndrome and Bilateral Optic Neuropathy After Kidney Transplantation

Touhami, Sara; Arzouk, Nadia; Darugar, Adil; Héron, Emmanuel; Clarençon, Frédéric; Bodaghi, Bahram; LeHoang, Phuc; Barrou, B.

doi:10.1097/tp.0000000000000551

Cited by 17 publications

(10 citation statements)

References 14 publications

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“…Alkylating agent/platinum Blurred vision, retinotoxicity (retinal ischaemia and neovascularization), optic neuropathy [33] Doxorubicin anthracyline drug conjunctivitis (m/c), periorbital edema, lacrimation, blepharospasm, keratitis, and decreased visual acuity [34] Everolimus mTOR inhibitor posterior reversible encephalopathy syndrome,bilateral optic neuropathy [35] Geftinib EGFR-inhibitor Dry eye, corneal ulcer [36,37] Gemcitabine antimetabolite agent uveal effusion and outer retinal disruption or Purtscher-like retinopathy with combination of docetaxel [25,38] Irinotecan topoisomerase I inhibitor None [39], none in combination regimen with 5-fluorouracil, oxaliplatin and bevacizumab [40] Oxaliplatin platinum dry eye, lacrimation, conjunctivitis, damage of the retinal pigment epithelium and the optic nerve, visual field defect [30,41] Paclitaxel Antimicrotubule agent epiphora, eye pain, conjunctivitis, blepharitis, blurred vision [24,42] Pemetrexed Antimetabolite /antifolate AION [1], eyelid edema [24,43] Ramucirumab monoclonal Ab of VEGFR-2 none [28] Sorafenib anti-VEGF agent blurred vision, periocular edema, retinal detachment, ptosis, optic neuropathy, macular edema [27,44] Temozolomide alkylating/methylating agent blurred vision with concurrent radiation therapy [45].…”

Section: Cisplatinmentioning

confidence: 99%

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

et al. 2020

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Background: We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials: Retrospective chart review. Results: Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions: EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops.

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Section: Cisplatinmentioning

confidence: 99%

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

et al. 2020

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“…Neurotoxicity with mTOR inhibitors is relatively low, however PRES associated with mTOR inhibitors was reported [134,162,202]. Sirolimus rarely causes neurotoxicity since it can alter cell metabolism of astrocytes, thus resulting in similar neurotoxicity as experienced by Tac and CsA (tremor, confusion, agitation and headache) [175].…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

“…For everolimus rare adverse effects are dizziness, hypoesthesia, paraesthesia, somnolence, and tremor [11]. Bilateral optic neuropathy was also reported [202]. As mentioned earlier, mTOR intermediates depression-like symptoms which may lead to corresponding psychiatric abnormalities during mTOR inhibitors use [2,237], although scarce evidence exists that mTOR inhibitors may have a more favourable profile than CNIs in this respect [111].…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

“…CsA, Tac, OKT3 [16,43,88,110,164,194], and as mentioned earlier -rituximab, belatacept and cyclophosphamide. Although neurotoxicity of mTOR inhibitors is relatively low, they can induce PRES in kidney transplantation patients [134,162,202]. Neurotoxicity is usually associated with higher serum concentrations of immunosuppressants, but may also become apparent at serum levels within the therapeutic range.…”

Section: Encephalopathymentioning

confidence: 99%

See 1 more Smart Citation

Neurologic complications in kidney transplant recipients

Piotrowski¹,

Lutkowska²,

Tsibulski³

et al. 2017

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Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections. Increasing age of transplant recipients and relaxation of transplantation eligibility criteria enriches the population with patients already compromised, with a higher present risk of stroke, neuropathy, malignancy etc. Research on and introduction to clinical practice of new agents like belatacept, proteasome inhibitors, or modified release formulations of tacrolimus, changes the picture and type of abnormalities within the nervous or neuromuscular system but does not eliminate them. Thus, it seems justified to remind the society of the whole array of neurologic complications they can see in their practice despite advances in the field..

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“…6 Although posterior reversible encephalopathy syndrome (PRES) has been commonly associated with calcineurin inhibitors, only a few reports of PRES associated with mTORi administration have been published. [7][8][9][10][11] As such, no combined brain and pulmonary lesions have been reported. To our knowledge, this is the 1st report concerning combined PRES and pneumonitis in a renal transplant recipient.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Gheith

Cerna

Halim³

et al. 2017

Exp Clin Transplant

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The mammalian target of rapamycin inhibitor siro limus was introduced into clinical transplant practice in 1999. Dose-related myelosuppression and hyper lipidemia are the most common adverse effects. Pulmonary toxicity has been reported since 2004 and can cause interstitial pneumonitis, organizing pneu monia, and alveolar hemorrhage. Moreover, it can occasionally induce posterior reversible encep halopathy syndrome, as documented in scarce reports. To our knowledge; this is the 1st report of combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis to be induced by sirolimus. Here, we present a renal transplant recipient with reversible sirolimusinduced brain lesions who was diagnosed after exclusion of infections (viral, bacterial, and fungal), tumors, sarcoidosis, and autoimmune disorders. Both brain lesions and pneumonitis resolved completely after sirolimus discontinuation with excellent patient and graft outcome. Early and gradual sirolimus withdrawal can reverse posterior reversible encephalopathy syndrome and lymphocytic pneumonitis with preservation of stable graft function.

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Everolimus-Induced Posterior Reversible Encephalopathy Syndrome and Bilateral Optic Neuropathy After Kidney Transplantation

Cited by 17 publications

References 14 publications

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

Neurologic complications in kidney transplant recipients

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