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have been also observed&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Contrariwise&#44; there are very limited data regarding autoimmune skin diseases following SARS-CoV-2 vaccines<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and there are only few reports of generalized morphea induced by COVID-19 mRNA vaccine&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 61-year-old Caucasian woman presented to our department with a 3-month history of ten&#44; symmetrical&#44; whitish&#44; xerotic and sclerotic plaques&#44; with a diameter ranging between 5&#8239;cm and 12&#8239;cm localized in the abdominal area&#44; lower limbs&#44; back and upper limbs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figs&#46; 1</a>A-B and <a class="elsevierStyleCrossRef" href="#fig0010">2</a>A&#41;&#46; A dermoscopy of one lesion showed prominent whitish fibrotic beams &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Her familiar and personal history was negative for autoimmune and chronic in&#64258;ammatory skin disorders&#46; She did never suffer from the Raynaud phenomenon&#44; and she did not present sclerodactyly&#44; with no facial involvement and no nail folds involvement&#46; The patient referred that the first lesions appeared in the abdominal area 15 days after the first dose of Comirnaty-Pfizer&#174; SARS-CoV-2 vaccine and lesions grew in number and size 15 days after the second dose of the vaccine&#46; The cutaneous lesions first arose as erythematous and itchy plaques&#44; becoming subsequently whitish and sclerotic&#46; A cutaneous biopsy of one lesion on the abdomen was performed&#46; The histology showed thickening and hyalinization of connective tissue of the deep dermis and subcutaneous fat&#44; with atrophy of adnexal structures&#44; increased fibroblasts&#44; and dense collagens through the deep dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Laboratory investigations showed the presence of antinuclear antibodies &#40;1&#58;160 in homogeneous pattern&#41;&#44; presence of antibodies anti-receptor-binding domain SARS-CoV-2 at 113&#8239;U&#47;mL &#40;normal values&#58; &#60;80&#8239;U&#47;mL&#41;&#44; while antibodies to extractable nuclear antigens were negative&#46; According to the clinical and histological correlation&#44; a final diagnosis of Generalized Morphea &#40;GM&#41; was performed and a therapy with clobetasol propionate 0&#46;05&#37; cream was started in association with a systemic treatment consisting in methotrexate 7&#46;5&#8239;mg per week&#44; with a single dose of 5&#8239;mg of folic acid once per week&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">GM is identified by more than four plaques&#44; at least 3&#8239;cm&#44; that involves two or more anatomical regions and differs from scleroderma by the absence of Raynaud phenomenon&#44; sclerodactyly&#44; facial involvement&#44; nail fold involvement&#44; and specific autoantibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In this case&#44; the onset of GM may be justified by the fact that vaccines can occasionally cause a new onset of &#64258;are of autoimmune-mediated diseases&#46; Indeed&#44; the spike protein of the SARS-CoV-2 vaccine shares genetic similarities with human proteins&#44; being an important factor that can trigger autoimmune diseases after vaccination due to molecular mimicry and generation of autoreactive lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> At the same time&#44; although the onset of cutaneous diseases after COVID-19 vaccines can highlight a causality association&#44; the very large number of cases receiving SARS-CoV-2 vaccines during the last months may induce biases&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> associating with vaccines also cutaneous manifestations that could have occurred independently&#46; In conclusion&#44; this is one of the few cases of GM arising after the SARS-CoV-2 vaccine and further cases are needed to better investigate a possible association of GM with this vaccination&#46; Reporting potential side effects of COVID-19 vaccines is important for daily clinical practice&#59; at the same time&#44; to date&#44; COVID-19 vaccines maintain a high safety profile&#44; and accordingly&#44; the population should not be discouraged from vaccinating&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Giovanni Paolino&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; writing of the manuscript or critical review of important intellectual content&#59; final approval of the final version of the manuscript&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Matteo Ricardo Di Nicola&#58; Writing of the manuscript or critical review of important intellectual content&#59; final approval of the final version of the manuscript&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nathalie Rizzo&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; final approval of the final version of the manuscript&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Santo Raffaele Mercuri&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; final approval of the final version of the manuscript&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Nathalie Rizzo and Santo Raffaele Mercuri share the co-last authorship&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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Letter - Clinical
Morphea after SARS-CoV2 vaccine
Giovanni Paolinoa, Matteo Riccardo Di Nicolaa,
Autor para correspondência
dinicola.matteo@hsr.it

Corresponding author.
, Nathalie Rizzob, Santo Raffaele Mercuria
a Unit of Dermatology and Cosmetology, IRCCS San Raffaele Hospital, Milano, Italy
b Surgical Pathology, IRCCS San Raffaele Hospital, Milano, Italy
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Symmetrical&#44; whitish&#44; ivory&#44; xerotic and sclerotic plaques&#44; with a diameter &#8805;3&#8239;cm&#46; &#40;B&#41; Whitish and sclerotic skin plaque with a &#8220;cigarette-paper&#8221; appearance on the patient&#39;s back&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Along with the increasing administration of COVID-19 vaccines&#44; in the last months&#44; the detection of potential adverse skin reactions has increased&#44; highlighting the possibility that not only SARS-CoV-2 infection but also COVID-19 vaccines can induce cutaneous manifestations&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> In this regard&#44; type I hypersensitivity reactions &#40;e&#46;g&#46;&#44; urticaria&#44; angioedema and anaphylaxis&#41; and type IV hypersensitivity reactions &#40;e&#46;g&#46;&#44; inflammatory reactions in the site of injection&#44; morbilliform and erythema multiforme-like rashes&#41; are the most commonly observed&#59; pityriasis rosea-like reactions&#44; herpes zoster reactivations and functional angiopathies &#40;e&#46;g&#46;&#44; chilblain-like lesions and erythromelalgia&#41; have been also observed&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Contrariwise&#44; there are very limited data regarding autoimmune skin diseases following SARS-CoV-2 vaccines<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and there are only few reports of generalized morphea induced by COVID-19 mRNA vaccine&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 61-year-old Caucasian woman presented to our department with a 3-month history of ten&#44; symmetrical&#44; whitish&#44; xerotic and sclerotic plaques&#44; with a diameter ranging between 5&#8239;cm and 12&#8239;cm localized in the abdominal area&#44; lower limbs&#44; back and upper limbs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figs&#46; 1</a>A-B and <a class="elsevierStyleCrossRef" href="#fig0010">2</a>A&#41;&#46; A dermoscopy of one lesion showed prominent whitish fibrotic beams &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Her familiar and personal history was negative for autoimmune and chronic in&#64258;ammatory skin disorders&#46; She did never suffer from the Raynaud phenomenon&#44; and she did not present sclerodactyly&#44; with no facial involvement and no nail folds involvement&#46; The patient referred that the first lesions appeared in the abdominal area 15 days after the first dose of Comirnaty-Pfizer&#174; SARS-CoV-2 vaccine and lesions grew in number and size 15 days after the second dose of the vaccine&#46; The cutaneous lesions first arose as erythematous and itchy plaques&#44; becoming subsequently whitish and sclerotic&#46; A cutaneous biopsy of one lesion on the abdomen was performed&#46; The histology showed thickening and hyalinization of connective tissue of the deep dermis and subcutaneous fat&#44; with atrophy of adnexal structures&#44; increased fibroblasts&#44; and dense collagens through the deep dermis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Laboratory investigations showed the presence of antinuclear antibodies &#40;1&#58;160 in homogeneous pattern&#41;&#44; presence of antibodies anti-receptor-binding domain SARS-CoV-2 at 113&#8239;U&#47;mL &#40;normal values&#58; &#60;80&#8239;U&#47;mL&#41;&#44; while antibodies to extractable nuclear antigens were negative&#46; According to the clinical and histological correlation&#44; a final diagnosis of Generalized Morphea &#40;GM&#41; was performed and a therapy with clobetasol propionate 0&#46;05&#37; cream was started in association with a systemic treatment consisting in methotrexate 7&#46;5&#8239;mg per week&#44; with a single dose of 5&#8239;mg of folic acid once per week&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">GM is identified by more than four plaques&#44; at least 3&#8239;cm&#44; that involves two or more anatomical regions and differs from scleroderma by the absence of Raynaud phenomenon&#44; sclerodactyly&#44; facial involvement&#44; nail fold involvement&#44; and specific autoantibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In this case&#44; the onset of GM may be justified by the fact that vaccines can occasionally cause a new onset of &#64258;are of autoimmune-mediated diseases&#46; Indeed&#44; the spike protein of the SARS-CoV-2 vaccine shares genetic similarities with human proteins&#44; being an important factor that can trigger autoimmune diseases after vaccination due to molecular mimicry and generation of autoreactive lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> At the same time&#44; although the onset of cutaneous diseases after COVID-19 vaccines can highlight a causality association&#44; the very large number of cases receiving SARS-CoV-2 vaccines during the last months may induce biases&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> associating with vaccines also cutaneous manifestations that could have occurred independently&#46; In conclusion&#44; this is one of the few cases of GM arising after the SARS-CoV-2 vaccine and further cases are needed to better investigate a possible association of GM with this vaccination&#46; Reporting potential side effects of COVID-19 vaccines is important for daily clinical practice&#59; at the same time&#44; to date&#44; COVID-19 vaccines maintain a high safety profile&#44; and accordingly&#44; the population should not be discouraged from vaccinating&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0020" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors&#8217; contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">Giovanni Paolino&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; writing of the manuscript or critical review of important intellectual content&#59; final approval of the final version of the manuscript&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Matteo Ricardo Di Nicola&#58; Writing of the manuscript or critical review of important intellectual content&#59; final approval of the final version of the manuscript&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nathalie Rizzo&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; final approval of the final version of the manuscript&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Santo Raffaele Mercuri&#58; Study concept and design&#59; intellectual participation in the propaedeutic and&#47;or therapeutic conduct of the studied cases&#59; final approval of the final version of the manuscript&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Nathalie Rizzo and Santo Raffaele Mercuri share the co-last authorship&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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