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Papillophlebitis versus pediatric venous thrombosis. A case with 46C/T polymorphism in the F12 coagulation gene
Papiloflebitis versus trombosis venosa pediátrica. Un caso con polimorfismo C46T del gen F12 de la coagulación
A. Gargallo-Benedicto
, M. Cerdà-Ibáñez, Á. Olate-Pérez, R. Clemente-Tomás, I. Almor Palacios, J.M. Hervás Hernandis, A. Duch-Samper
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Servicio de Oftalmología, Hospital Clínico Universitario de Valencia, Valencia, Spain
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Nazar, M. Feldman, R. González, R. Espinoza" "autores" => array:4 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Nazar" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Feldman" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "González" ] 3 => array:2 [ "nombre" => "R." 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A case with 46C/T polymorphism in the F12 coagulation gene" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "291" "paginaFinal" => "294" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Gargallo-Benedicto, M. Cerdà-Ibáñez, Á. Olate-Pérez, R. Clemente-Tomás, I. Almor Palacios, J.M. Hervás Hernandis, A. Duch-Samper" "autores" => array:7 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Gargallo-Benedicto" "email" => array:1 [ 0 => "amparolinares_88@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Cerdà-Ibáñez" ] 2 => array:2 [ "nombre" => "Á." "apellidos" => "Olate-Pérez" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Clemente-Tomás" ] 4 => array:2 [ "nombre" => "I." "apellidos" => "Almor Palacios" ] 5 => array:2 [ "nombre" => "J.M." "apellidos" => "Hervás Hernandis" ] 6 => array:2 [ "nombre" => "A." "apellidos" => "Duch-Samper" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Oftalmología, Hospital Clínico Universitario de Valencia, Valencia, 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" => "Papiloflebitis versus trombosis venosa pediátrica. Un caso con polimorfismo C46T del gen F12 de la coagulación" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 578 "Ancho" => 1301 "Tamanyo" => 130939 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Macular OCT showing macular edema after 2 days.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Clinic case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">An 8-year-old child without relevant pathological history was referred to ophthalmological emergencies due to sudden and progressive loss of visual acuity (VA) in the left eye (LE) with 24<span class="elsevierStyleHsp" style=""></span>h evolution, without associated symptomatology. Ophthalmological examination showed VA of 1 in the right eye (RE) and 0.1 in the LE, with discrete left relative afferent pupillary defect (RAPD). Slitlamp biomicroscopy showed normal anterior pole. LE funduscopy revealed congestive and hyperemic papilla, with venous tortuosity and peripapillary hemorrhages. Contralateral eye exploration produced no relevant results. Directed anamnesis did not produce personal or familial traumatic, systemic or ophthalmological antecedents. Emergency examination discarded alterations in hemogram, biochemistry, coagulation and ECG. Possible differential diagnostics included anterior optical neuritis (papillitis) or occlusive etiology. The child was admitted for anti-aggregate treatment with AAS 150<span class="elsevierStyleHsp" style=""></span>mg.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Evolution checkup 2 days later showed persistence of congestion and papillary hyperemia, peripapillary hemorrhages and flame hemorrhages with cotton-like exudates over venous arcades (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) together with macular edema through optical coherence tomography (OCT) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Diagnosis leaned towards retinal central vein occlusion (thrombosis versus papilloflebitis). No vascular sheathing or vitritis were observed. Cerebral magnetic resonance produced normal results. Serology study for HIV, syphilis and Varicella zoster was negative. Similarly, no anomalies were found in self-immunity parameters.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Fluorescein angiography revealed delays in venous filling with hyperfluorescence due to extravasation at the papillary level, without signs of ischemia or peripheral vasculitis (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Subsequently it was decided to initiate anticoagulant therapy with enoxaparin (1<span class="elsevierStyleHsp" style=""></span>mg/kg/12<span class="elsevierStyleHsp" style=""></span>h).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">A complete study of thrombophilia and coagulation disorders produced polymorphism C46T heterozygosis bearer of coagulation gene F12 as sole finding.</p><p id="par0025" class="elsevierStylePara elsevierViewall">During the first months of evolution, the lesions in ocular fundus and macular edema diminished (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). At month 6, anticoagulant treatment was suspended. At the time of writing, after 8 months of evolution, the patient exhibited complete resolution of said lesions and VA of 1 in the LE.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">In 1961, Lyle and Wybar<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> described for the first time the term “retinal vasculitis” to describe a unilateral clinic condition coursing with loss of vision, venous tortuosity, retinal hemorrhages and papillary edema, with positive evolution, in which they suspected central retinal vein occlusion secondary to inflammatory vasculitis of the venous system. Subsequently, Lonn and Hoyt (1966)<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> redefined said term as papilloflebitis, and Cogan in 1968,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Hart et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> in 1971 and Hayreh in 1972<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> presented new similar cases. At present, this is an infrequent entity typically affecting young healthy patients unilaterally. It is regarded as a form of inflammatory non-ischemic retinal central vein occlusion that courses with ophthalmoscopic and angiographic characteristics similar to central retinal vein thrombosis, the evolution of which is generally benign. The visual prognosis is positive and the majority of cases do not require treatment although it is advisable to preventively treat with anti-aggregates and maintain follow-up to avoid possible complications such as neovascularization, macular edema or even macular hole. However, not all authors agree on the etiology of the condition and it is crucial to discard primary or secondary vasculitis, uveitis, papillitis and thrombosis of the central retinal vein as underlying mechanism.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The presentation of retinal venous thrombosis in pediatric patients is exceptional and is generally associated to cephalic traumatisms, hyperviscosity syndromes, coagulation disorders, inflammatory processes such as vasculitis and more rarely to compressive diseases. Accordingly, directed anamnesis and complete systemic study are fundamental for differential diagnostic and therapeutic approach of these patients. Due to the ophthalmological characteristics and evolution, the present case could be due to papillophlebitis giving rise to differential diagnostic with pediatric central retinal vein thrombosis with positive prognosis.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7,8</span></a> Even though anti-aggregate treatment is generally advised, papillophlebitis present positive evolution and the majority of cases are resolved without requiring treatment. In the present case, anti-aggregants and anticoagulant therapy were applied, obtaining the resolution of the condition. However, it has not been demonstrated that said treatment improves the evolution of this disease. Mutation C46T of Factor 12 involves a risk factor for venous thrombosis,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> coronary disease and stroke. When presenting in homozygosis, the risk of thromboembolic disease is 5 times higher than in non-bearers, even though the association has not been established for heterozygote bearers. To date, retinal venous occlusion related to this mutation has not been reported in the literature.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have not received financial support.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interests</span><p id="par0045" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres845237" "titulo" => "Abstract" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Clinical case" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec840119" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres845236" "titulo" => "Resumen" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec840118" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinic case report" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Funding" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-08-01" "fechaAceptado" => "2016-08-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec840119" "palabras" => array:4 [ 0 => "Papillophlebitis" 1 => "Central retinal vein occlusion" 2 => "Retinal vasculitis" 3 => "Genetic polymorphism" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec840118" "palabras" => array:4 [ 0 => "Papiloflebitis" 1 => "Oclusión vena central retina" 2 => "Vasculitis retiniana" 3 => "Polimorfismo genético" ] ] ] ] "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">An 8-year-old boy with no known diseases, with sudden loss of visual acuity (VA) in the left eye (LE). Examination: VA 1 in right eye, and 0.1 in LE, discrete left relative afferent pupil defect (RAPD). Normal biomicroscopy. Funduscopy: congestive papilla, venous tortuosity, peripapillary hemorrhages with macular edema in LE. The systemic study only revealed A C46Tpolymorphism in the F12 coagulation gene. He had a VA of 1 and normal funduscopy 8 months later.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Papillophlebitis is an inflammatory and non-ischemic central retinal vein occlusion, ophthalmoscopically similar to central retinal vein thrombosis. The systemic study is essential to rule out underlying diseases.</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">Niño de 8 años, sin enfermedades, con pérdida brusca de la agudeza visual (AV) en el ojo izquierdo (OI). Exploración: AV 1 en el OD y 0,1 en el OI, discreto DPAR izquierdo. Biomicroscopía normal. Fundoscopía: papila congestiva, tortuosidad venosa, hemorragias peripapilares con edema macular en el OI. El estudio sistémico únicamente reveló polimorfismo C46T del gen F12 de la coagulación. Ocho meses después: AV de 1 con fundoscopía normal.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discusión</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La papiloflebitis es una oclusión de la vena central de la retina (VCR) inflamatoria no isquémica, oftalmoscópicamente semejante a las trombosis de VCR. El estudio sistémico es fundamental para descartar enfermedades subyacentes.</p></span>" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "abst0015" "titulo" => "Caso clínico" ] 1 => array:2 [ "identificador" => "abst0020" "titulo" => "Discusión" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gargallo-Benedicto A, Cerdà-Ibáñez M, Olate-Pérez Á, Clemente-Tomás R, Almor Palacios I, Hervás Hernandis JM, et al. Papiloflebitis versus trombosis venosa pediátrica. Un caso con polimorfismo C46T del gen F12 de la coagulación. Arch Soc Esp Oftalmol. 2017;92:291–294.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This paper was partially presented at the 92nd Congress of the Ophthalmology Society of Spain, Málaga, September 2016.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 888 "Ancho" => 900 "Tamanyo" => 103645 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Left eye retinography, showing congestion and papillary hyperemia, venous tortuosity and peripapillary hemorrhages.</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" => 578 "Ancho" => 1301 "Tamanyo" => 130939 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Macular OCT showing macular edema after 2 days.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 703 "Ancho" => 900 "Tamanyo" => 55872 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Fluorescein angiography in venous time, with late hyperfluorescence due to extravasation at the papillary level.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 888 "Ancho" => 900 "Tamanyo" => 107967 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Resolution of lesions in checkup retinography at 1 month of evolution.</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" => "Retinal vasculitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.K. 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