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had been on natalizumab since 2010&#46; She presented to our clinic in 2018 showing the presence of indurated plaques on both abdominal flanks&#46; Suspecting localized plaque morphea&#44; a skin biopsy was performed&#44; which confirmed typical changes including dermal sclerosis and loss of skin appendages &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; General laboratory tests and serologies&#44; including for <span class="elsevierStyleItalic">Borrelia burgdorferi</span>&#44; were normal or negative&#46; A 4-month regimen of clobetasol propionate 0&#46;05&#37; was administered&#44; 20 days a month&#46; After observing little improvement&#44; topical photochemotherapy &#40;PUVA&#41; was applied&#44; with complete remission of the lesions after a total dose of 6<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span>&#46; Three months after finishing treatment&#44; the patient returned&#44; perceiving tension and hardening of the arms and legs&#46; Physical examination revealed generalized induration of all extremities&#44; bilaterally and symmetrically&#44; sparing the trunk&#44; hands&#44; and feet&#44; which prevented pinching and gave an orange peel appearance &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figs&#46; 2A and B</a>&#41;&#46; Suspecting EF&#44; a deep biopsy&#44; including the fascia&#44; was performed&#44; which was consistent with the diagnosis&#44; showing superficial and deep cutaneous sclerosis&#44; as well as fascial thickening associated with a mixed infiltrate of lymphocytes&#44; eosinophils&#44; and a few plasma cells &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figs&#46; 3A and B</a>&#41;&#46; A complete blood count revealed eosinophilia and elevated acute phase reactants&#44; with persistently negative <span class="elsevierStyleItalic">Borrelia</span> serology&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After reviewing the literature&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> natalizumab was recommended to be discontinued&#44; and oral prednisone was down titrated with an initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#44; and PUVA was administered with partial improvement&#46; However&#44; lesions relapsed after prednisone was down titrated &#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The neurology service discontinued natalizumab and changed it for ocrelizumab&#44; which was started 6 months later&#44; without evidence of relapses of her neurological disease in this interval&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the second dose of ocrelizumab&#44; there was progressive improvement in the skin condition&#44; allowing the discontinuation of PUVA and oral prednisone 8 months after starting it&#46; Since then&#44; the patient has remained asymptomatic both cutaneous and neurologically&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">EF is characterized by acute or subacute hardening of the skin of the extremities bilaterally and symmetrically&#44; sparing the hands and feet&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> It starts with a sensation of pain or tightness in the skin that progresses into overt hardening&#44; resulting from the development of sclerotic bands between the deep dermis and fascia&#44; giving the clinical appearance of &#8220;orange peel&#8221;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a> It has been reported that up to 30&#37; of patients present with typical localized plaque morphea lesions&#44; which can appear before&#44; synchronously&#44; or months after EF&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Known triggers include strenuous exercise&#44; trauma&#44; insect bites&#44; and multiple drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are 2 articles in the literature linking natalizumab&#44; a humanized recombinant antibody used in MS treatment&#44; with the development of EF&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> These are 2 isolated cases where the clinical condition developed within the first year of treatment&#44; with rapid improvement after discontinuation&#44; but no relapse after reintroduction&#46; According to updated WHO causality criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> both in these cases and ours&#44; the association between the drug and the disease would only be possible&#46; Specifically&#44; in our case&#44; the timing and lack of improvement upon discontinuing natalizumab lead us to consider other possible triggers&#44; and in this regard&#44; we find a well-documented association in the literature between EF and other autoimmune diseases&#44; including another case of MS treated with fumarates&#46;<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&#44; 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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
B. Vázquez Losadaa,
Corresponding author
bvazlosada@gmail.com

Corresponding author.
, M. García Martínezb, W.J. Villafani Echazuc, Y. Hidalgo Garcíaa
a Servicio de Dermatología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
b Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
c Servicio de Neurología, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Localized plaque morphea and eosinophilic fasciitis &#40;EF&#41; are entities included in sclerodermiform syndromes&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a> Although their pathophysiological mechanism remains unknown to thos date&#44; they have been associated with the consumption of multiple drugs since their description&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> There are published cases linking the use of natalizumab&#8212;a monoclonal antibody used for the treatment of multiple sclerosis&#8212;with the development of these entities&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;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&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 39-year-old woman with multiple sclerosis &#40;MS&#41; had been on natalizumab since 2010&#46; She presented to our clinic in 2018 showing the presence of indurated plaques on both abdominal flanks&#46; Suspecting localized plaque morphea&#44; a skin biopsy was performed&#44; which confirmed typical changes including dermal sclerosis and loss of skin appendages &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; General laboratory tests and serologies&#44; including for <span class="elsevierStyleItalic">Borrelia burgdorferi</span>&#44; were normal or negative&#46; A 4-month regimen of clobetasol propionate 0&#46;05&#37; was administered&#44; 20 days a month&#46; After observing little improvement&#44; topical photochemotherapy &#40;PUVA&#41; was applied&#44; with complete remission of the lesions after a total dose of 6<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span>&#46; Three months after finishing treatment&#44; the patient returned&#44; perceiving tension and hardening of the arms and legs&#46; Physical examination revealed generalized induration of all extremities&#44; bilaterally and symmetrically&#44; sparing the trunk&#44; hands&#44; and feet&#44; which prevented pinching and gave an orange peel appearance &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figs&#46; 2A and B</a>&#41;&#46; Suspecting EF&#44; a deep biopsy&#44; including the fascia&#44; was performed&#44; which was consistent with the diagnosis&#44; showing superficial and deep cutaneous sclerosis&#44; as well as fascial thickening associated with a mixed infiltrate of lymphocytes&#44; eosinophils&#44; and a few plasma cells &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figs&#46; 3A and B</a>&#41;&#46; A complete blood count revealed eosinophilia and elevated acute phase reactants&#44; with persistently negative <span class="elsevierStyleItalic">Borrelia</span> serology&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After reviewing the literature&#44;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> natalizumab was recommended to be discontinued&#44; and oral prednisone was down titrated with an initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#44; and PUVA was administered with partial improvement&#46; However&#44; lesions relapsed after prednisone was down titrated &#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The neurology service discontinued natalizumab and changed it for ocrelizumab&#44; which was started 6 months later&#44; without evidence of relapses of her neurological disease in this interval&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the second dose of ocrelizumab&#44; there was progressive improvement in the skin condition&#44; allowing the discontinuation of PUVA and oral prednisone 8 months after starting it&#46; Since then&#44; the patient has remained asymptomatic both cutaneous and neurologically&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">EF is characterized by acute or subacute hardening of the skin of the extremities bilaterally and symmetrically&#44; sparing the hands and feet&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> It starts with a sensation of pain or tightness in the skin that progresses into overt hardening&#44; resulting from the development of sclerotic bands between the deep dermis and fascia&#44; giving the clinical appearance of &#8220;orange peel&#8221;&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a> It has been reported that up to 30&#37; of patients present with typical localized plaque morphea lesions&#44; which can appear before&#44; synchronously&#44; or months after EF&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Known triggers include strenuous exercise&#44; trauma&#44; insect bites&#44; and multiple drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are 2 articles in the literature linking natalizumab&#44; a humanized recombinant antibody used in MS treatment&#44; with the development of EF&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#44;5</span></a> These are 2 isolated cases where the clinical condition developed within the first year of treatment&#44; with rapid improvement after discontinuation&#44; but no relapse after reintroduction&#46; According to updated WHO causality criteria&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> both in these cases and ours&#44; the association between the drug and the disease would only be possible&#46; Specifically&#44; in our case&#44; the timing and lack of improvement upon discontinuing natalizumab lead us to consider other possible triggers&#44; and in this regard&#44; we find a well-documented association in the literature between EF and other autoimmune diseases&#44; including another case of MS treated with fumarates&#46;<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&#44; 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ISSN: 00017310
Original language: English
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