Letter to the Editor
Necrotizing herpetic retinopathy in kidney-transplanted patients on mycophenolate mofetil
Retinopatía necrosante herpética en trasplantado renal con mofetil micofenolato
Manuel Morión Grandea, M. Adoración Martín-Gómezb,
, Aurora Quereda Castañedaa, Verónica López Jiménezc, Teresa Cabezas Fernándezd
Corresponding author
a Servicio de Oftalmología, Hospital de Poniente, El Ejido, Almería, Spain
b Unidad de Nefrología, Hospital de Poniente, El Ejido, Almería, Spain
c Unidad de Trasplante Renal, Servicio de Nefrología, Hospital Regional de Málaga, Málaga, Spain
d Unidad de Microbiología, Hospital de Poniente, El Ejido, Almería, Spain
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(B) Funduscopy: moderate vitritis, optic nerve swelling and white-yellowish lesions in the upper and lower temporal nasal retina.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 73-year-old male, with a kidney transplant in December 2006, and treated with mycophenolate mofetil (MMF) 500<span class="elsevierStyleHsp" style=""></span>mg/d and tacrolimus. In April 2012, he was admitted to another hospital for diffuse cutaneous varicella, which progressed favourably with oral acyclovir; source of infection unknown. In December 2012, he attended A&E at our hospital for one-week of history of floaters and decreased vision in the left eye. An ophthalmologic and funduscopic examination revealed retinitis of the affected eye with a visual acuity (VA) of 20/100 and an intraocular pressure of 18<span class="elsevierStyleHsp" style=""></span>mmHg with a normal contralateral eye (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). PCR and viral serologic testing (IgG and IgM), and then a test for the varicella zoster virus (VZV), were negative (negative pre-transplant). A sample of aqueous humour from the anterior chamber for an analysis of viral DNA was obtained, and intravenous acyclovir was prescribed (the patient refused immediate intravitreal treatment). The patient's clinical progress was satisfactory, with rapid improvement after 11 days (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and initiation of a complete regression of lesions was evident. The PCR of aqueous humour confirmed that it was a VZV infection, and the rest of tests was negative. 360° laser photocoagulation of the retina was performed, while continuing with oral acyclovir. The patient was discharged 20 days after admission, with VA 20/32. Twelve weeks later, he presented with rhegmatogenous retinal detachment, which, despite a successful replication by <span class="elsevierStyleItalic">pars plana</span> vitrectomy with scleral buckling and silicone oil, failed to achieve more than 20/200. Three years later, he has a VA of just light perception and residual inferior retinal detachment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The incidence of VZV in the general population increases with age after, the age of 50. However, disseminated varicella is a rare presentation even in immunosuppressed patients, and when it occurs, it is usually during the first year after transplantation.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This patient presented with clinical symptoms 9 years post-transplant with minimal doses of immunosuppression and without steroid therapy. His pre-transplant serology was negative, and so a primary infection due to varicella zoster was assumed; but he remained negative after 9 months of the cutaneous episode, which can be explained by the anergy of immunosuppression. To date, peri-transplant prophylaxis with acyclovir is not indicated in seronegative cases, but vaccination for VZV in waitlist patients, done at our centre since 2010, may reduce the incidence of this infection.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The time elapsed between the skin symptoms and the onset of retinopathy indicates virus latency in neurons. Primary VZV infection typically occurs in childhood, infecting the epidermal cells and causing the characteristic skin rash. Subsequently, the sensory nerve terminals of mucocutaneous tissue are infected reaching through axons the sensory roots of the dorsal root ganglia, where it remains dormant in neuronal bodies. Reactivation occurs with new virions in sensory neurons that migrate again through the axons to the epidermis (neuropathic pain and rash). It is known that cellular immune suppression plays an important role in this reactivation, such that these patients will present with VZV more often, with a prevalence between 3% and 14%.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Routine ophthalmologic examinations should be considered in patients with opportunistic viral infections. Retinal complications are rare,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and amongst their most common causes is external progressive acute retinal necrosis (ARN), retinitis caused by cytomegalovirus (CMV) and toxoplasmosis. Necrotizing herpetic retinopathies are caused by VZV, herpes simplex virus I and II, CMV, and rarely, Epstein–Barr virus.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Their most common presentations are decreased vision, pain and photophobia.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> On examination, multifocal yellowish-white patches are typical, which tend to coalesce in diffuse areas of full-thickness retinal necrosis. Other signs of ocular inflammation, such as vitritis, vasculitis, optic disc swelling, keratic precipitate and posterior synechiae, may accompany them. ARN is an ophthalmological emergency in which antiviral treatment should be started early, as it leads to blindness due to retinal scarring, retinal detachment or optic nerve atrophy. In addition, one-third of patients develop bilateral involvement within the first month of presentation.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The development of VZV in the transplant population has been associated to MMF<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a> This is due to viral thymidine kinase, which replaces the inosine monophosphate dehydrogenase inhibited by mycophenolate, thus allowing the cell to continue its life cycle. However, the specific involvement in this disease is not clear if compared with other immunosuppressants in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In addition, MMF has been shown to play certain role in enhancing the antiviral activity of acyclovir.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Thus the role of MMF in this type of viral infection or in this patient is not clear, especially when considering the low dose used. Clinical practice suggests that once disseminated disease presents, it makes sense to reduce the immunosuppressive burden, given the high morbidity and mortality of this disease.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morión Grande M, Martín-Gómez MA, Quereda Castañeda A, López Jiménez V, Cabezas Fernández T. Retinopatía necrosante herpética en trasplantado renal con mofetil micofenolato. Nefrologia. 2016;36:575–577.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 586 "Ancho" => 1599 "Tamanyo" => 85211 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Inflammatory reaction in the anterior chamber with thin retrokeratic precipitate, also discrete ciliary injection and a dense grade 5 cataract, LOCS II. (B) Funduscopy: moderate vitritis, optic nerve swelling and white-yellowish lesions in the upper and lower temporal nasal retina.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 731 "Ancho" => 995 "Tamanyo" => 82029 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Upper nasal lesion with sharper edges and start of pigmentation in areas in resolution.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disseminated varicella zoster virus infection in adult renal transplant recipients: outcome and risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 3 | 6 |
| 2024 October | 51 | 54 | 105 |
| 2024 September | 42 | 24 | 66 |
| 2024 August | 63 | 70 | 133 |
| 2024 July | 49 | 43 | 92 |
| 2024 June | 53 | 33 | 86 |
| 2024 May | 72 | 44 | 116 |
| 2024 April | 51 | 33 | 84 |
| 2024 March | 37 | 32 | 69 |
| 2024 February | 46 | 31 | 77 |
| 2024 January | 34 | 23 | 57 |
| 2023 December | 32 | 31 | 63 |
| 2023 November | 57 | 30 | 87 |
| 2023 October | 32 | 21 | 53 |
| 2023 September | 28 | 31 | 59 |
| 2023 August | 39 | 16 | 55 |
| 2023 July | 35 | 22 | 57 |
| 2023 June | 30 | 29 | 59 |
| 2023 May | 48 | 28 | 76 |
| 2023 April | 29 | 15 | 44 |
| 2023 March | 60 | 16 | 76 |
| 2023 February | 45 | 18 | 63 |
| 2023 January | 33 | 20 | 53 |
| 2022 December | 59 | 32 | 91 |
| 2022 November | 59 | 32 | 91 |
| 2022 October | 83 | 54 | 137 |
| 2022 September | 49 | 29 | 78 |
| 2022 August | 51 | 44 | 95 |
| 2022 July | 53 | 35 | 88 |
| 2022 June | 56 | 36 | 92 |
| 2022 May | 77 | 29 | 106 |
| 2022 April | 87 | 41 | 128 |
| 2022 March | 90 | 37 | 127 |
| 2022 February | 91 | 50 | 141 |
| 2022 January | 80 | 30 | 110 |
| 2021 December | 63 | 39 | 102 |
| 2021 November | 59 | 39 | 98 |
| 2021 October | 43 | 38 | 81 |
| 2021 September | 56 | 29 | 85 |
| 2021 August | 59 | 41 | 100 |
| 2021 July | 74 | 39 | 113 |
| 2021 June | 40 | 30 | 70 |
| 2021 May | 72 | 42 | 114 |
| 2021 April | 113 | 91 | 204 |
| 2021 March | 82 | 53 | 135 |
| 2021 February | 60 | 25 | 85 |
| 2021 January | 32 | 24 | 56 |
| 2020 December | 52 | 20 | 72 |
| 2020 November | 38 | 16 | 54 |
| 2020 October | 34 | 13 | 47 |
| 2020 September | 41 | 25 | 66 |
| 2020 August | 46 | 11 | 57 |
| 2020 July | 40 | 22 | 62 |
| 2020 June | 27 | 14 | 41 |
| 2020 May | 53 | 22 | 75 |
| 2020 April | 24 | 24 | 48 |
| 2020 March | 32 | 13 | 45 |
| 2020 February | 36 | 24 | 60 |
| 2020 January | 41 | 21 | 62 |
| 2019 December | 55 | 27 | 82 |
| 2019 November | 37 | 26 | 63 |
| 2019 October | 26 | 7 | 33 |
| 2019 September | 27 | 14 | 41 |
| 2019 August | 29 | 21 | 50 |
| 2019 July | 27 | 22 | 49 |
| 2019 June | 36 | 18 | 54 |
| 2019 May | 23 | 17 | 40 |
| 2019 April | 53 | 23 | 76 |
| 2019 March | 37 | 20 | 57 |
| 2019 February | 20 | 28 | 48 |
| 2019 January | 42 | 18 | 60 |
| 2018 December | 128 | 33 | 161 |
| 2018 November | 220 | 9 | 229 |
| 2018 October | 172 | 17 | 189 |
| 2018 September | 84 | 12 | 96 |
| 2018 August | 68 | 14 | 82 |
| 2018 July | 64 | 13 | 77 |
| 2018 June | 54 | 12 | 66 |
| 2018 May | 87 | 13 | 100 |
| 2018 April | 94 | 8 | 102 |
| 2018 March | 112 | 11 | 123 |
| 2018 February | 113 | 7 | 120 |
| 2018 January | 131 | 7 | 138 |
| 2017 December | 138 | 10 | 148 |
| 2017 November | 61 | 17 | 78 |
| 2017 October | 38 | 7 | 45 |
| 2017 September | 37 | 18 | 55 |
| 2017 August | 28 | 6 | 34 |
| 2017 July | 24 | 4 | 28 |
| 2017 June | 28 | 15 | 43 |
| 2017 May | 21 | 5 | 26 |
| 2017 April | 31 | 5 | 36 |
| 2017 March | 20 | 29 | 49 |
| 2017 February | 17 | 2 | 19 |
| 2017 January | 37 | 10 | 47 |
| 2016 December | 12 | 3 | 15 |
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