Case and Research Letters
Refractory Eosinophilic Fasciitis: Good Response to Ocrelizumab in a Patient with Multiple Sclerosis Under Treatment with Natalizumab
Fascitis eosinofílica refractaria en un paciente con esclerosis múltiple en tratamiento con natalizumab: respuesta al ocrelizumab
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H-E staining. Checkerboard hyperkeratosis, alternating areas of orthokeratosis with parakeratosis, and apoptotic keratinocytes in the form of colloid bodies (*) in the epidermis.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Oteiza Rius, J. Antoñanzas Pérez, A. Morelló Vicente, A. España" "autores" => array:4 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Oteiza Rius" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Antoñanzas Pérez" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Morelló Vicente" ] 3 => array:2 [ "nombre" => "A." 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Note the improvement of the lesions after 6 months of treatment with apremilast 30<span class="elsevierStyleHsp" style=""></span>mg twice a day (C and D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Mansilla-Polo, C. Abril-Pérez, M.Á. Navarro-Mira, R. Botella-Estrada" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Mansilla-Polo" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Abril-Pérez" ] 2 => array:2 [ "nombre" => "M.Á." "apellidos" => "Navarro-Mira" ] 3 => array:2 [ "nombre" => "R." 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H-E (2<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleSmallCaps">×</span>, 20<span class="elsevierStyleHsp" style=""></span>×). Morfea en placas. Biopsia cutánea con una marcada pérdida de los anejos cutáneos y la presencia de abundantes bandas de fibrosis que ocupan la dermis media y profunda. B. Detalle de unas bandas colágenas engrosadas, hallazgos sugestivos de una morfea en placas.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Vázquez Losada, M. García Martínez, W.J. Villafani Echazu, Y. Hidalgo García" "autores" => array:4 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Vázquez Losada" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "García Martínez" ] 2 => array:2 [ "nombre" => "W.J." "apellidos" => "Villafani Echazu" ] 3 => array:2 [ "nombre" => "Y." "apellidos" => "Hidalgo García" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731023004179?idApp=UINPBA000044" "url" => "/00017310/unassign/S0001731023004179/v1_202401062102/es/main.assets" ] ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => " Refractory Eosinophilic Fasciitis: Good Response to Ocrelizumab in a Patient with Multiple Sclerosis Under Treatment with Natalizumab" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor,</span>" "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "B. Vázquez Losada, M. García Martínez, W.J. Villafani Echazu, Y. Hidalgo García" "autores" => array:4 [ 0 => array:4 [ "nombre" => "B." "apellidos" => "Vázquez Losada" "email" => array:1 [ 0 => "bvazlosada@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "García Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "W.J." "apellidos" => "Villafani Echazu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Y." "apellidos" => "Hidalgo García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fascitis eosinofílica refractaria en un paciente con esclerosis múltiple en tratamiento con natalizumab: respuesta al ocrelizumab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 406 "Ancho" => 1003 "Tamanyo" => 76127 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span> and <span class="elsevierStyleBold">B.</span> H-E (2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>, 20<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>). Eosinophilic fasciitis. <span class="elsevierStyleBold">A</span>. Thick bands of sclerosis in the hypodermis. <span class="elsevierStyleBold">B.</span> Presence of eosinophils in the subcutaneous tissue and hypodermis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Localized plaque morphea and eosinophilic fasciitis (EF) are entities included in sclerodermiform syndromes.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> Although their pathophysiological mechanism remains unknown to thos date, they have been associated with the consumption of multiple drugs since their description.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> There are published cases linking the use of natalizumab—a monoclonal antibody used for the treatment of multiple sclerosis—with the development of these entities.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe a case of both signs in a patient on natalizumab who required a change of treatment to ocrelizumab for control.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 39-year-old woman with multiple sclerosis (MS) had been on natalizumab since 2010. She presented to our clinic in 2018 showing the presence of indurated plaques on both abdominal flanks. Suspecting localized plaque morphea, a skin biopsy was performed, which confirmed typical changes including dermal sclerosis and loss of skin appendages (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). General laboratory tests and serologies, including for <span class="elsevierStyleItalic">Borrelia burgdorferi</span>, were normal or negative. A 4-month regimen of clobetasol propionate 0.05% was administered, 20 days a month. After observing little improvement, topical photochemotherapy (PUVA) was applied, with complete remission of the lesions after a total dose of 6<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span>. Three months after finishing treatment, the patient returned, perceiving tension and hardening of the arms and legs. Physical examination revealed generalized induration of all extremities, bilaterally and symmetrically, sparing the trunk, hands, and feet, which prevented pinching and gave an orange peel appearance (<a class="elsevierStyleCrossRef" href="#fig0010">Figs. 2A and B</a>). Suspecting EF, a deep biopsy, including the fascia, was performed, which was consistent with the diagnosis, showing superficial and deep cutaneous sclerosis, as well as fascial thickening associated with a mixed infiltrate of lymphocytes, eosinophils, and a few plasma cells (<a class="elsevierStyleCrossRef" href="#fig0015">Figs. 3A and B</a>). A complete blood count revealed eosinophilia and elevated acute phase reactants, with persistently negative <span class="elsevierStyleItalic">Borrelia</span> serology.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After reviewing the literature,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> natalizumab was recommended to be discontinued, and oral prednisone was down titrated with an initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day, and PUVA was administered with partial improvement. However, lesions relapsed after prednisone was down titrated <<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg/day.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The neurology service discontinued natalizumab and changed it for ocrelizumab, which was started 6 months later, without evidence of relapses of her neurological disease in this interval.</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the second dose of ocrelizumab, there was progressive improvement in the skin condition, allowing the discontinuation of PUVA and oral prednisone 8 months after starting it. Since then, the patient has remained asymptomatic both cutaneous and neurologically.</p><p id="par0035" class="elsevierStylePara elsevierViewall">EF is characterized by acute or subacute hardening of the skin of the extremities bilaterally and symmetrically, sparing the hands and feet.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> It starts with a sensation of pain or tightness in the skin that progresses into overt hardening, resulting from the development of sclerotic bands between the deep dermis and fascia, giving the clinical appearance of “orange peel”.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> It has been reported that up to 30% of patients present with typical localized plaque morphea lesions, which can appear before, synchronously, or months after EF.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Known triggers include strenuous exercise, trauma, insect bites, and multiple drugs.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are 2 articles in the literature linking natalizumab, a humanized recombinant antibody used in MS treatment, with the development of EF.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> These are 2 isolated cases where the clinical condition developed within the first year of treatment, with rapid improvement after discontinuation, but no relapse after reintroduction. According to updated WHO causality criteria,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> both in these cases and ours, the association between the drug and the disease would only be possible. Specifically, in our case, the timing and lack of improvement upon discontinuing natalizumab lead us to consider other possible triggers, and in this regard, we find a well-documented association in the literature between EF and other autoimmune diseases, including another case of MS treated with fumarates.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Ocrelizumab is a humanized anti-CD20 monoclonal antibody approved by the FDA in 2017 for the treatment of MS, with a similar mechanism of action to rituximab. Since there are 8 cases in the literature of refractory EF with a good response to rituximab,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> we expected disease control with this drug, being, to date, the first case ever reported of EF responding to ocrelizumab described in the literature. We believe it is important to highlight the efficacy of this drug and consider it in refractory cases.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 568 "Ancho" => 1003 "Tamanyo" => 120697 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span> and <span class="elsevierStyleBold">B.</span> H-E (2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>, 20<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>). Localized plaque morphea. Skin biopsy with marked loss of skin appendages and presence of abundant bands of fibrosis occupying the mid and deep dermis. <span class="elsevierStyleBold">B.</span> Detail of thickened collagen bands, findings suggestive of localized plaque morphea.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 674 "Ancho" => 1005 "Tamanyo" => 74629 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span> and <span class="elsevierStyleBold">B.</span> Clinical appearance of the patient. <span class="elsevierStyleBold">A.</span> Orange peel skin and rope sign in both popliteal fossae. <span class="elsevierStyleBold">B.</span> Difficulty pinching the skin due to marked hardening.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 406 "Ancho" => 1003 "Tamanyo" => 76127 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span> and <span class="elsevierStyleBold">B.</span> H-E (2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>, 20<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>). Eosinophilic fasciitis. <span class="elsevierStyleBold">A</span>. Thick bands of sclerosis in the hypodermis. <span class="elsevierStyleBold">B.</span> Presence of eosinophils in the subcutaneous tissue and hypodermis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diffuse fasciitis with hypergammaglobulinemia and eosinophilia: A new syndrome?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L.E. 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