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Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission
Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa
J.D. Saldaña Garrido
, M. Martínez Rubio, R. Carrión Campo, M.A. Moya Moya, L. Rico Sergado
Corresponding author
Unidad de Retina, Servicio de Oftalmología, Hospital General Universitario de Alicante, Alicante, Spain
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"apellidos" => "Díaz-Cabanas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669116300818" "doi" => "10.1016/j.oftal.2016.05.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669116300818?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579417300178?idApp=UINPBA00004N" "url" => "/21735794/0000009200000003/v1_201703010038/S2173579417300178/v1_201703010038/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "145" "paginaFinal" => "148" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J.D. Saldaña Garrido, M. Martínez Rubio, R. Carrión Campo, M.A. Moya Moya, L. Rico Sergado" "autores" => array:5 [ 0 => array:4 [ "nombre" => "J.D." "apellidos" => "Saldaña Garrido" "email" => array:1 [ 0 => "jdsalga@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Martínez Rubio" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Carrión Campo" ] 3 => array:2 [ "nombre" => "M.A." "apellidos" => "Moya Moya" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Rico Sergado" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Unidad de Retina, Servicio de Oftalmología, Hospital General Universitario de Alicante, Alicante, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 738 "Ancho" => 900 "Tamanyo" => 120659 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Full resolution of papiledema after treatment with chemotherapy and radiotherapy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">T-cell acute lymphoblastic leukemia (T-ALL) is a malign lymphoproliferative disease that can cause extra medullary organic infiltration. Ocular involvement occurs in 90% of these patients, being the third most frequent extramedullary expression after the meninges and testicles,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> associating poor prognosis particularly with medullar relapse or involvement of the central nervous system (CNS).</p><p id="par0010" class="elsevierStylePara elsevierViewall">Ocular expressions in acute leukemia are more frequent<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> and are variable, severe, with rapid development and frequently prior to hematological expression. Optic nerve infiltration is 13–18%,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> which is highly significant as it could be the first sign of extramedullary relapse after complete remission,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> and could involve the SNC.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> It usually appears in the course of ALL, and its treatment is complex due to poor penetration of chemotherapy. The treatment of choice is high doses of focal radiotherapy (over 30<span class="elsevierStyleHsp" style=""></span>Gy) and intrathecal chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Prognosis is poor, particularly if it arises during treatment, with a survival rate of 50% at 6 months and 10% at one year.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Cytomegalovirus (CMV) retinitis in ALL is the most frequent opportunistic infection, usually arising during the maintenance phase in patients with hematopoietic cell transplant.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Its diagnostic is mainly clinic.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinic case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">Female, 43 years with T-ALL diagnostic in complete remission and in maintenance treatment with methotrexate and mercaptopurine, referred to the Ophthalmology Department due to suspected herpetic retinal necrosis vs leukaemic retinitis in the left eye (LE).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Personal records include high risk T-ALL and pulmonary thromboembolism. Ophthalmological examination revealed a visual acuity of light perception in the right eye (RE) and of 1 in the LE. The anterior pole was normal. Ocular fundus showed retinal ischemia in posterior pole with dispersed hemorrhages, peripheral retinal necrosis with full retina detachment (RD) in RE and retinitis area with hemorrhages in the upper peripheral retina and lower nasal in LE (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">After discarding hematological relapse of the disease (medullary puncture was negative) and on the basis of RE examination, the diagnostic of herpetic retinal necrosis was established, treated with intravenous acyclovir at high doses and 3 intravitreal injections of ganciclovir at 0.2<span class="elsevierStyleHsp" style=""></span>mg/0.1<span class="elsevierStyleHsp" style=""></span>ml. in addition, the vitreous was biopsied for PCR for the herpesvirus group and toxoplasmosis with negative results.</p><p id="par0035" class="elsevierStylePara elsevierViewall">After 15 days of treatment, insidious progression of the lesions was observed leading to the suspicion of CMV retinitis, substituting acyclovir by intravenous foscarnet. With this change of treatments edema and number of hemorrhages diminished. However, 26 days later the patient referred pain and RE supraduction limitation as well as papiledema in the LE (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Magnetic resonance showed orbital leukemic infiltration in the RE and of the optic nerve in the LE. In addition, a lumbar puncture isolated blasts in the cerebrospinal fluid, enabling the diagnostic of leukaemic relapse.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment was established with intrathecal chemotherapy (FLAG-IDA), radiotherapy of the optic nerve and corticotherapy, with full resolution of the ocular lesions (<a class="elsevierStyleCrossRefs" href="#fig0020">Figs. 4–6</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">In a patient with ALL exhibiting ocular expressions it is crucial to determine whether the involvement is leukemic infiltration or an opportunistic infection. Complete clinical records and physical examination must be carried out, requesting information about immunosuppressant treatments, bone marrow transplants, corticoids etc. It is also important to make a blood analysis with full cell count, chest X-ray, lumbar puncture and magnetic resonance (the imaging test of choice if suspected CNS involvement<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6</span></a>).</p><p id="par0055" class="elsevierStylePara elsevierViewall">In the presence of signs of active disease, the probable diagnostic is leukaemic relapse. However, in the absence of signs of activity, it is likely to be an opportunistic infection, in which case it is recommended to initiate empirical treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the present case, RE involvement and the presence of peripheral retinitis with only a few hemorrhages in the LE led to the initial suspicion of retinal necrosis, initiating treatment with intravenous acyclovir plus intravitreal acyclovir. Oral therapy was utilized as maintenance treatment.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The suspicion of CNV retinitis arose subsequently due to the behavior of the lesions as well as the absence of granulomatous uveitis and vitritis (constant in retinitis due to herpes simplex virus). In addition, medullary punctures were negative, which initially led to discarding leukemic relapse.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Optic nerve infiltration is more frequent in acute leukemia and could preceed optic hematological relapse by several months. Chemotherapy has low intraorbital penetration, making external radiotherapy the indicated treatment.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Some cases suggest that patients in the maintenance phase could be immunodepressed, which implies the need to watch for the possibility of opportunistic infections such as CMV.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">In accordance with the above, it is recommended to make a complete ophthalmological study in the presence of ocular symptoms, even in remission, as early diagnostic and treatment could improve the visual and vital prognosis of the patients.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Funding</span><p id="par0085" class="elsevierStylePara elsevierViewall">No source of funding has been received for this clinic case report.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres807383" "titulo" => "Abstract" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Clinical case" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec805283" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres807384" "titulo" => "Resumen" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec805284" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-08-13" "fechaAceptado" => "2016-05-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec805283" "palabras" => array:7 [ 0 => "Acute leukaemia" 1 => "Leukaemic retinitis" 2 => "Cytomegalovirus retinitis" 3 => "Papillitis" 4 => "Ocular involvement" 5 => "Leukaemic relapse" 6 => "Optic nerve infiltration" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec805284" "palabras" => array:7 [ 0 => "Leucemia aguda" 1 => "Retinitis leucémica" 2 => "Retinitis por citomegalovirus" 3 => "Papilitis" 4 => "Afectación ocular" 5 => "Recaída leucémica" 6 => "Infiltración de nervio óptico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Clinical case</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A 43-year-old woman in remission from T-cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal hemorrhage. The patient was treated for cytomegalovirus retinitis after an extended hematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ocular involvement may precede hematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Clinical case" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Discussion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Caso clínico</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mujer de 43 años con leucemia linfoblástica T en remisión completa, remitida por sospecha de necrosis retiniana herpética/retinitis leucémica en el ojo izquierdo (OI). La agudeza visual era de unidad y el fondo de ojo presentaba retinitis y hemorragias en periferia. Ante estudio hematológico negativo, recibió tratamiento por retinitis por citomegalovirus. Tras mejoría inicial, aparece papilitis en el OI y restricción de la motilidad en el ojo derecho. La resonancia y punción lumbar confirman la recidiva leucémica.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discusión</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La afectación ocular puede preceder a la recaída hematológica, por eso debe sospecharse ante sintomatología ocular. Además, son frecuentes las infecciones oportunistas en inmunodeprimidos.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Saldaña Garrido JD, Martínez Rubio M, Carrión Campo R, Moya Moya MA, Rico Sergado L. Infiltración leucémica y retinitis por citomegalovirus en paciente con leucemia linfoblástica aguda tipo T en remisión completa. 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