Letter to the Editor
Refractory juvenile dermatomyositis: Response to tofacitinib
Dermatomiositis juvenil refractaria: respuesta al tofacitinib
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(B) X-ray findings of calcification on the patient's two legs, after 17 months’ treatment with tofacitinib, calcifications regressed. In (A), the white dot image in the figure is calcification as shown by the red arrow. In (B), the calcification as shown by the red arrow has disappeared.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Juvenile dermatomyositis (JDM) is a chronic systemic autoimmune disease, mainly manifested as muscle weakness and rash, which can also be accompanied by calcifications and even involves lung, heart and other organs. Hence, it is necessary to adopt timely and effective therapy to stop the progression of the disease damage. Glucocorticoids and disease modifying anti-rheumatic drugs (DMARDs) are a main therapy. However, patients with JDM who are unresponsive to corticosteroids or other immunosuppressive medications face poor outcome and suffer from various sequelae of the disease.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> Therefore, it is important to find new treatments for refractory JDM. Recently, multiple centers have tried biologics including rituximab, abatacept, tofacitinib and tocilizumab for refractory dermatomyositis. Though some trials fail to reach its primary end point, janus-Kinase (JAK) inhibitor tofacitinib for refractory dermatomyositis patients showed an overall good efficacy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In JDM, type I interferon participates in the pathophysiological process by inducing the expression of proinflammatory cytokines. In addition, STAT3 can be transferred to mitochondria and might involve in regulating the release of mitochondrial calcium pool. This is of potential significance to calcification in patients with dermatomyositis. Herein, JAK inhibitors may be a meaningful treatment for JDM with calcification.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> We did like to report a successful case of treating extensive calcifications in refractory JDM with tofacitinib.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our patient was a 2.1-year-old child whose clinical manifestation is severe proximal muscle weakness, with the score on the childhood myositis assessment scale (CMAS) score of 26/52 and Gottron's papules over his hands’ small and large joints. His both legs were covered with lumps. The results of laboratory tests showed the following abnormal values: high lactate dehydrogenase (LDH<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>387<span class="elsevierStyleHsp" style=""></span>U/L, reference range 155–345<span class="elsevierStyleHsp" style=""></span>U/L) and erythrocyte sedimentation rate (ESR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>43<span class="elsevierStyleHsp" style=""></span>mm/h, reference range 0–15<span class="elsevierStyleHsp" style=""></span>mm/h). Antinuclear antibodies were positive with a titer of 1:100. The myositis-specific autoantibodies screening demonstrated positive anti-NXP2 and X-ray of thighs demonstrated extensive deep calcium deposits. Biopsy for the subcutaneous mass on the left leg showed calcified nodules, and biopsy for the muscle showed inflammatory musculopathy, which are consistent with muscle damage changes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">According to the Bohan and Peter criteria, the patient was diagnosed with cutaneous calcinosis with JDM. He started to be treated with oral prednisolone 2<span class="elsevierStyleHsp" style=""></span>mg/kg/day, intravenous immunoglobulin 2<span class="elsevierStyleHsp" style=""></span>g/kg), subcutaneous methotrexate, oral cyclosporine (5<span class="elsevierStyleHsp" style=""></span>mg/kg/day). As a result, the laboratory tests significantly improved thanks to the treatment. CMAS score was from 26/52 to 36/52 and the skin lesions slightly improved, but this cannot prevent the progression of calcifications (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">So he began to be treated with tofacitinib at 4 because of muscle weakness without complete remission and progression in calcifications. He accepted dose escalation until the optimal tolerated treatment doses applicable to his weight and renal function (5<span class="elsevierStyleHsp" style=""></span>mg/day). Six months later, the skin lesions saw complete remission and CMAS score was from 36/52 to 40/52, and physician global VAS score from 8 to 4. Inflammation of calcifications were fully resolved. 17 months later, CMAS score was from 40/52 to 48/52, physician global VAS score from 4 to 2 and calcifications became either stable or regressive. There were no new lumps underneath the skin (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). During the treatment with tofacitinib, there was no hospitalization due to infectious diseases. The number of white blood cells had never decreased seriously (3.87–10.00<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L), so had the number of neutrophils (2.39–4.34<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/L). Blood lipids, liver enzymes and creatinine were within the normal ranges.</p><p id="par0030" class="elsevierStylePara elsevierViewall">This is consistent with the report of Yuchuan Ding and his colleagues (2020), which highlighted tofacitinib in significantly improving the rash and muscle strength of 25 refractory JDM patients.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> We observed that tofacitinib also can prevent rapidly progressive calcification, and some calcifications began to shrink when being treated with tofacitinib. Tofacitinib may be an effective and safe therapy for extensive calcifications in refractory JDM patients. But our case has been a difficulty for many years, so the possibility of its symptoms to be completely reversible still remains uncertain. However, for the first time in two years, we are able to significantly change the process of calcification, which proved that the symptoms have improved. Further prospective studies are required to explore the potential safety and efficacy of JDM in JAK inhibitor.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethics approval and consent to participate</span><p id="par0035" class="elsevierStylePara elsevierViewall">In the study, the use of human data was clearly approved by the Ethics Committee of Shenzhen Children's Hospital, and obtained the informed consents of the patient’ parents.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundings</span><p id="par0040" class="elsevierStylePara elsevierViewall">This study was supported by <span class="elsevierStyleGrantSponsor" id="gs1">Sanming Project of Medicine in Shenzhen</span> (<span class="elsevierStyleGrantNumber" refid="gs1">SZSM201812002</span>) and <span class="elsevierStyleGrantSponsor" id="gs2">Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties</span> (No. <span class="elsevierStyleGrantNumber" refid="gs2">SZGSP012</span>).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">All the authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethics approval and consent to participate" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Fundings" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "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" => 1558 "Ancho" => 2500 "Tamanyo" => 203816 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) X-ray findings of calcification on the patient's two legs before being treated with tofacitinib, there were a lot of calcifications on both legs. (B) X-ray findings of calcification on the patient's two legs, after 17 months’ treatment with tofacitinib, calcifications regressed. In (A), the white dot image in the figure is calcification as shown by the red arrow. In (B), the calcification as shown by the red arrow has disappeared.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical practice guidance for juvenile dermatomyositis (JDM) 2018-update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I. Kobayashi" 1 => "S. Akioka" 2 => "N. Kobayashi" 3 => "N. Iwata" 4 => "S. Takezaki" 5 => "H. 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Zhou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/annrheumdis-2020-218582" "Revista" => array:2 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2020" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000002/v1_202201220701/S2387020621006951/v1_202201220701/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015800000002/v1_202201220701/S2387020621006951/v1_202201220701/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621006951?idApp=UINPBA00004N" ]
