Letter to the Editor
Rheumatoid Arthritis and Ocular Myasthenia Gravis: Effectiveness of Rituximab in the Management of These Two Diseases
Artritis reumatoide y miastenia gravis ocular: efectividad del rituximab en el manejo de ambas enfermedades
Marta Novella-Navarro
, Juan Salvatierra-Ossorio, María del Mar Muñoz-Gómez, María Pavo-Blanco
Corresponding author
Servicio de Reumatología, Hospital Clínico Universitario San Cecilio, Granada, Spain
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"apellidos" => "Cordova Cassia" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574318300327?idApp=UINPBA00004M" "url" => "/21735743/0000001400000003/v1_201805120507/S2173574318300327/v1_201805120507/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Rheumatoid Arthritis and Ocular Myasthenia Gravis: Effectiveness of Rituximab in the Management of These Two Diseases" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "179" "paginaFinal" => "180" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Marta Novella-Navarro, Juan Salvatierra-Ossorio, María del Mar Muñoz-Gómez, María Pavo-Blanco" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Marta" "apellidos" => "Novella-Navarro" "email" => array:1 [ 0 => "mnovellanavarro@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Juan" "apellidos" => "Salvatierra-Ossorio" ] 2 => array:2 [ "nombre" => "María del Mar" "apellidos" => "Muñoz-Gómez" ] 3 => array:2 [ "nombre" => "María" "apellidos" => "Pavo-Blanco" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Reumatología, Hospital Clínico Universitario San Cecilio, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Artritis reumatoide y miastenia <span class="elsevierStyleItalic">gravis</span> ocular: efectividad del rituximab en el manejo de ambas enfermedades" ] ] "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" => 913 "Ancho" => 1693 "Tamanyo" => 87729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Monitoring of the levels of rheumatoid factor (RF), anti-acetylcholine receptor (anti-AChR) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in terms of the clinical response to rituximab (RTX). There was a progressive decrease in anti-AChR which was not detectable following the fourth dose.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Myasthenia gravis (MG) is an autoimmune disease that affects the neuromuscular junction of the striated muscles. It provokes a fluctuating weakness of the voluntary muscles, mainly due to the direct attack of autoantibodies against the acetylcholine receptor (AChR).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Our patient was a 66-year-old woman, diagnosed with rheumatoid arthritis (RA) in 2012. She was being treated with 20<span class="elsevierStyleHsp" style=""></span>mg/week of methotrexate. After 23 months of good clinical control, her disease became active, and treatment was begun with etanercept at 50<span class="elsevierStyleHsp" style=""></span>mg/week. After 6 doses of etanercept, she came to the emergency department with complete ptosis of right eye with a fluctuating course, that had developed 3 days earlier. She had a limitation of upgaze and, thus, was admitted by the neurology department with suspected ocular MG. During her hospital stay, she underwent brain magnetic resonance imaging and chest computed tomography, both of which were normal. Laboratory tests showed normal erythrocyte sedimentation rate and C-reactive protein, antinuclear antibodies and extractable nuclear antigens were negative, rheumatoid factor was 232<span class="elsevierStyleHsp" style=""></span>IU/mL (normal level 0–14), anti-cyclic citrullinated peptide antibodies >300<span class="elsevierStyleHsp" style=""></span>IU/mL (0–20) and anti-AChR antibodies 29.52<span class="elsevierStyleHsp" style=""></span>nmol/L (0–0.25). Electromyogram revealed an increase in mean jitter, presence of right frontalis muscle blocks and a decrease in the amplitude at rest of facial nerve signal to nasalis muscle, compatible with a postsynaptic neuromuscular transmission defect. With the confirmation of the diagnosis of ocular MG, it was decided to discontinue etanercept. Three weeks after the interruption of etanercept therapy, which was replaced by 30<span class="elsevierStyleHsp" style=""></span>mg/day of prednisone, the patient's neurological status improved. However, over the course of 12 weeks, during which the prednisone dose was being tapered, she developed a polyarticular flare and the ocular symptoms reappeared. It was decided to administer a course of rituximab (2 doses of 500<span class="elsevierStyleHsp" style=""></span>mg separated by 15 days), followed by retreatment (500<span class="elsevierStyleHsp" style=""></span>mg every 6 months), with which control of the joint and neurological symptoms was achieved (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Approximately 5% of the population has one or more autoimmune diseases, and the prevalence is highest in middle-aged women.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> Patients who have an autoimmune disease are more susceptible to developing a second one. Myasthenia gravis is associated with RA in up to 4% of the patients.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This association may be due to immunological factors that favor the activation of autoreactive B and T cells, epigenetic factors and genetic susceptibility to certain groups of genes, particularly those belonging to the major histocompatibility complex.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Thus, if we consider that the overlap of autoimmune disorders is a reflection of the existence of common pathogenic mechanisms, the therapeutic approach should be the same.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Anti-tumor necrosis factor alpha (TNFα) agents have favored the treatment and prognosis of rheumatic diseases like RA, in addition to being employed in other autoimmune diseases. In fact, etanercept has produced satisfactory results in the treatment of refractory MG,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> with no effect on serum anti-AChR levels or changes in circulating TNFα. Paradoxically, the literature includes the report of 1 case of MG in a patient with RA being treated with etanercept,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> in whom the discontinuation of the drug resulted in the improvement of the myasthenic signs.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Although there is no clear causal association, the development of neurological disorders, especially demyelinating diseases (Guillain-Barré syndrome, multiple sclerosis, mononeuritis or chronic demyelinating polyneuropathy<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6,7</span></a>), has occasionally been related to anti-TNFα agents. Should they occur, the main recommendation is to discontinue the treatment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In the present case, there existed the possibility of there being an association between 2 autoimmune diseases or, on the other hand, a probable adverse effect of etanercept. The decision was made to interrupt the drug and begin treatment with rituximab, the utility of which has been reported in the treatment of refractory MG.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> Its mechanism of action provokes a depletion of B cells and the resulting reduction in antibodies, enabling the clinical control of both diseases. The doses administered are generally 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>, with retreatment every 6 months given the half-life of this agent,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> although there is still no consensus concerning the guidelines for its administration in MG.</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: Novella-Navarro M, Salvatierra-Ossorio J, Muñoz-Gómez MM, Pavo-Blanco M. Artritis reumatoide y miastenia <span class="elsevierStyleItalic">gravis</span> ocular: efectividad del rituximab en el manejo de ambas enfermedades. Reumatol Clin. 2018;14:179–180.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 913 "Ancho" => 1693 "Tamanyo" => 87729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Monitoring of the levels of rheumatoid factor (RF), anti-acetylcholine receptor (anti-AChR) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in terms of the clinical response to rituximab (RTX). There was a progressive decrease in anti-AChR which was not detectable following the fourth dose.</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" => "Myasthenia gravis: an update for the clinician" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.P. 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Goldstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mus.21521" "Revista" => array:6 [ "tituloSerie" => "Muscle Nerve" "fecha" => "2010" "volumen" => "41" "paginaInicial" => "375" "paginaFinal" => "378" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19852027" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001400000003/v1_201805120507/S2173574318300315/v1_201805120507/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001400000003/v1_201805120507/S2173574318300315/v1_201805120507/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574318300315?idApp=UINPBA00004M" ]
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| 2024 January | 161 | 26 | 187 |
| 2023 December | 96 | 31 | 127 |
| 2023 November | 102 | 25 | 127 |
| 2023 October | 139 | 38 | 177 |
| 2023 September | 137 | 33 | 170 |
| 2023 August | 95 | 17 | 112 |
| 2023 July | 101 | 24 | 125 |
| 2023 June | 84 | 19 | 103 |
| 2023 May | 115 | 19 | 134 |
| 2023 April | 86 | 19 | 105 |
| 2023 March | 139 | 26 | 165 |
| 2023 February | 116 | 29 | 145 |
| 2023 January | 121 | 8 | 129 |
| 2022 December | 117 | 34 | 151 |
| 2022 November | 107 | 30 | 137 |
| 2022 October | 134 | 38 | 172 |
| 2022 September | 131 | 35 | 166 |
| 2022 August | 136 | 26 | 162 |
| 2022 July | 161 | 42 | 203 |
| 2022 June | 96 | 28 | 124 |
| 2022 May | 200 | 35 | 235 |
| 2022 April | 222 | 37 | 259 |
| 2022 March | 193 | 46 | 239 |
| 2022 February | 186 | 24 | 210 |
| 2022 January | 174 | 40 | 214 |
| 2021 December | 114 | 37 | 151 |
| 2021 November | 125 | 44 | 169 |
| 2021 October | 183 | 46 | 229 |
| 2021 September | 122 | 35 | 157 |
| 2021 August | 129 | 42 | 171 |
| 2021 July | 142 | 18 | 160 |
| 2021 June | 222 | 28 | 250 |
| 2021 May | 126 | 41 | 167 |
| 2021 April | 356 | 108 | 464 |
| 2021 March | 179 | 28 | 207 |
| 2021 February | 149 | 28 | 177 |
| 2021 January | 109 | 25 | 134 |
| 2020 December | 151 | 25 | 176 |
| 2020 November | 120 | 24 | 144 |
| 2020 October | 129 | 22 | 151 |
| 2020 September | 121 | 31 | 152 |
| 2020 August | 219 | 21 | 240 |
| 2020 July | 85 | 33 | 118 |
| 2020 June | 77 | 22 | 99 |
| 2020 May | 51 | 15 | 66 |
| 2020 April | 19 | 23 | 42 |
| 2020 March | 27 | 6 | 33 |
| 2019 May | 1 | 0 | 1 |
| 2018 September | 1 | 0 | 1 |
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