Case Report
Scleroderma “en coup de sabre” With Epilepsy and Uveitis Successfully Treated With Tocilizumab
La esclerodermia «en coup de sabre» con epilepsia y uveítis se trata con éxito con tocilizumab
Maria Osminina
, Nathalia Geppe, Elena Afonina
Corresponding author
Department of Pediatrics, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
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At the ECG sinus tachycardia and ST-segment elevation from V2-V6 are visible (red arrows); the CXR shows cardiomegaly (yellow arrow) and bilateral pulmonary congestion (red arrows). Middle, the same tests at discharge. ECG with sinus rhythm and deep negative T waves from V2-V6 and in I and AvL (red arrows); CXR with clear lung fields. Botton, ECG and CXR 3 months after the episode. ECG shows normalization of the T wave, and CXR is normal. Panel 2: A: Echocardiogram at admission showing severe LV dysfunction (28.7% calculated by Simpson method). B: four chambers views from the echocardiogram at admission showing pericardial effusion (red arrow). C: short-axis view from a Cardiac MR (STIR sequence) showing more white density in the anterior and septum zone suggesting myocardial edema (red arrow). 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Sechenov First Moscow State Medical University, Moscow, Russia" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La esclerodermia «en coup de sabre» con epilepsia y uveítis se trata con éxito con tocilizumab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1567 "Ancho" => 2167 "Tamanyo" => 253966 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Disease development.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Linear scleroderma “en coup de sabre” (LSCS) is a subset of linear scleroderma, affecting frontopariental region, with frequent neurological and ophthalmological involvement. Neurological symptoms (NS) in LSCS are presented with epilepsy, headache, focal neurologic deficits, movement disorders, neuropsychiatric symptoms and ocular involvement including anterior uveitis, episcleritis, glaucoma and keratitis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Based on the most accepted hypothesis NS in LSCS are caused by neurovasculitis and focal cerebral inflammation.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2–4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">A Caucasian girl of 2 years 10 months developed vomiting, weakness in left hand, loss of consciousness, over a period of a month – partial clonic seizures with left clonic jerks and, loss of consciousness. Cerebral MRI revealed areas of hyperintense signals in white matter of the periventricular zone of the body, front and rear horn of the right lateral ventricle of the brain. Criptogenic focal epilepsy was diagnosed, she was given carbomazepine 16<span class="elsevierStyleHsp" style=""></span>mg\kilo, and seizures stopped.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Two months later an ivory-colored skin spot with violaceous borders with induration and hyperpigmentation appeared on in the middle of forehead (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In four months asymmetry of her face, linear alopecia of the right frontoparietal zone were noticed. Seizures renewed and, the right iridocyclitis outbursted. The diagnose of LSCS was made. Physical and instrumental examination found no internal organ involvement but MRI and EEG showed brain lesions. Laboratory tests showed elevated serum Ig G level and rheumatoid factor.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Treatment with oral prednisone 1<span class="elsevierStyleHsp" style=""></span>mg\kg.b.w\daily was started for 10 weeks, then tapped and methotrexate (MTX) 10<span class="elsevierStyleHsp" style=""></span>mg\b.sq.\weekly, carbomazepin retard 300<span class="elsevierStyleHsp" style=""></span>mg daily, folic acid, local treatment of skin lesions. During the first 2 months the condition of the patient improved, she stopped seizures and skin progression. But, at the daily prednisone dose 17.5<span class="elsevierStyleHsp" style=""></span>mg, skin process relapsed. MTX dose was increased to 12<span class="elsevierStyleHsp" style=""></span>mg\b.sq. During the following 10 months the patients’ condition was stable. Nevertheless, in 16 months of treatment epileptic activity and skin progression restarted, uveitis activated. Brain MRI showed the enlargement of periventricular white matter lesion, up to 30<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>mm (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Disease development is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Uneffectiveness of immunodepressant treatment forced us to initialize a biologic agent. We started Tz infusions 10<span class="elsevierStyleHsp" style=""></span>mg\kg once in 4 weeks, accompanied by prednisone 5<span class="elsevierStyleHsp" style=""></span>mg\daily, MTX 12<span class="elsevierStyleHsp" style=""></span>mg\b.sq\w., additionally – topiromat and valproic acid. Monthly infusions of Tz were continuated for 26 months, prednisone was stopped after 2 months and MTX in 4 months after initiation of Tz treatment. Thus, for the latter 20 months the patient received only Tz. Cerebral MRI performed after 6 months of Tz therapy showed diminution of periventricular focus in white matter to 27<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>13<span class="elsevierStyleHsp" style=""></span>mm. Distinct reduction of foci (23<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>11<span class="elsevierStyleHsp" style=""></span>mm) was found after 12 months of Tz treatment (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Skin ivory colored spots and induration disappeared, the intensity of fibrotic lesions decreased, hair start to grow in the area of alopecia. There were no seizures, EEG pattern improved, so valproic acid was stopped, no relapses of uveitis were detected.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Therapy with Tz lasted for 26 months, when repeated cerebral MRI showed the absence of previous foci in the brain (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). We stopped Tz infusions, but reinduced MTX injections weekly (12<span class="elsevierStyleHsp" style=""></span>mg\b.sq). Follow up period of 12 months, shows no disease progression, the girl continue MTX treatment.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">This case report shows dramatic improvement after Tz treatment in a girl with convention treatment resistant LCDS. Hyperintense lesions on T2-weighted MRI documented an acute inflammatory process in the brain,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> as a result the neurovasculitis – a part of systemic vascular disfunction in scleroderma. The severity of neurovasculitis was resistant to conventional immunodepressant therapy, but Tz produced strong antiinflammatory effect and the white matter lesions disappeared. The efficacy of Tz suggests, that neurovaculitis in scleroderma may be reversible, which correlates with the other publications.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">There are similar publications on promising results of Tz in scleroderma,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7–9</span></a> further investigations are needed to evaluate indications for biologics in scleroderma with NS involvement.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">There were no funding or granting of work.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">There is no conflict of interests among the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1374668" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1262811" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1374669" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1262812" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "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" => "2017-12-14" "fechaAceptado" => "2018-05-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1262811" "palabras" => array:3 [ 0 => "Scleroderma “en coup de sabre” with neurovasculitis" 1 => "Epilepsy and uveitis" 2 => "Tocilizumab treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1262812" "palabras" => array:3 [ 0 => "Esclerodermia «en coup de sabre» con neurovasculitis" 1 => "Epilepsia y uveítis" 2 => "Tratamiento con tocilizumab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Case history of a small girl outlet with epilepsy, followed by scleroderma skin damage and uveitis, neurovasculitis with white matter foci in brain on the side of skin lesion in two months, immunologic disease activity. Resistance to conventional immunosuppressive therapy forced us to initiate the treatment with tocilizumab. It was well tolerated and led to significant improvement of brain, ocular and skin manifestations.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Historia de la enfermedad de una niña con epilepsia, así como las lesiones cutáneas de la esclerodermia y la uveítis, la neurovasculitis con materia blanca se centra en el cerebro en el lado de la lesión de la piel en 2 meses, la actividad de las enfermedades inmunológicas. La resistencia a la terapia inmunosupresora tradicional nos hizo comenzar el tratamiento con tocilizumab. Fue bien tolerado y condujo a una mejoría significativa en las manifestaciones cerebrales, oculares y de la piel.</p></span>" ] ] "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" => 1567 "Ancho" => 2167 "Tamanyo" => 253966 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Disease development.</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" => 1080 "Ancho" => 2917 "Tamanyo" => 298716 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">MRI investigation of the brain (A) before Tz treatment, (B) MRI investigation of the brain in 12 months Tz treatment and (C) MRI investigation of the brain in 26 months Tz treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Juvenile localized scleroderma: clinical and epidemiological features in 750 children. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 1 | 6 |
| 2024 October | 30 | 22 | 52 |
| 2024 September | 46 | 15 | 61 |
| 2024 August | 54 | 28 | 82 |
| 2024 July | 44 | 24 | 68 |
| 2024 June | 44 | 24 | 68 |
| 2024 May | 34 | 20 | 54 |
| 2024 April | 51 | 16 | 67 |
| 2024 March | 39 | 26 | 65 |
| 2024 February | 41 | 22 | 63 |
| 2024 January | 46 | 27 | 73 |
| 2023 December | 38 | 19 | 57 |
| 2023 November | 46 | 35 | 81 |
| 2023 October | 26 | 27 | 53 |
| 2023 September | 48 | 38 | 86 |
| 2023 August | 32 | 11 | 43 |
| 2023 July | 47 | 19 | 66 |
| 2023 June | 40 | 19 | 59 |
| 2023 May | 34 | 21 | 55 |
| 2023 April | 43 | 5 | 48 |
| 2023 March | 46 | 30 | 76 |
| 2023 February | 34 | 19 | 53 |
| 2023 January | 48 | 9 | 57 |
| 2022 December | 48 | 20 | 68 |
| 2022 November | 44 | 28 | 72 |
| 2022 October | 43 | 19 | 62 |
| 2022 September | 31 | 18 | 49 |
| 2022 August | 38 | 34 | 72 |
| 2022 July | 47 | 30 | 77 |
| 2022 June | 45 | 33 | 78 |
| 2022 May | 57 | 32 | 89 |
| 2022 April | 40 | 29 | 69 |
| 2022 March | 34 | 37 | 71 |
| 2022 February | 57 | 19 | 76 |
| 2022 January | 56 | 34 | 90 |
| 2021 December | 23 | 30 | 53 |
| 2021 November | 38 | 34 | 72 |
| 2021 October | 44 | 37 | 81 |
| 2021 September | 36 | 36 | 72 |
| 2021 August | 25 | 30 | 55 |
| 2021 July | 22 | 36 | 58 |
| 2021 June | 20 | 19 | 39 |
| 2021 May | 25 | 37 | 62 |
| 2021 April | 78 | 59 | 137 |
| 2021 March | 39 | 21 | 60 |
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