An unusual anti–melanoma differentiation–associated protein 5 amyopathic dermatomyositis
Identifieur interne : 000307 ( Pmc/Corpus ); précédent : 000306; suivant : 000308An unusual anti–melanoma differentiation–associated protein 5 amyopathic dermatomyositis
Auteurs : Héloïse Barailler ; Sophie Charles ; Felix Goutorbe ; Suzanne DevauxSource :
- JAAD Case Reports [ 2352-5126 ] ; 2019.
Url:
DOI: 10.1016/j.jdcr.2019.02.019
PubMed: 31008175
PubMed Central: 6454120
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PMC:6454120Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An unusual anti–melanoma differentiation–associated protein 5 amyopathic dermatomyositis</title><author><name sortKey="Barailler, Heloise" sort="Barailler, Heloise" uniqKey="Barailler H" first="Héloïse" last="Barailler">Héloïse Barailler</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Charles, Sophie" sort="Charles, Sophie" uniqKey="Charles S" first="Sophie" last="Charles">Sophie Charles</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Goutorbe, Felix" sort="Goutorbe, Felix" uniqKey="Goutorbe F" first="Felix" last="Goutorbe">Felix Goutorbe</name><affiliation><nlm:aff id="aff2">Department of Gastroenterology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Devaux, Suzanne" sort="Devaux, Suzanne" uniqKey="Devaux S" first="Suzanne" last="Devaux">Suzanne Devaux</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31008175</idno><idno type="pmc">6454120</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454120</idno><idno type="RBID">PMC:6454120</idno><idno type="doi">10.1016/j.jdcr.2019.02.019</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000307</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000307</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An unusual anti–melanoma differentiation–associated protein 5 amyopathic dermatomyositis</title><author><name sortKey="Barailler, Heloise" sort="Barailler, Heloise" uniqKey="Barailler H" first="Héloïse" last="Barailler">Héloïse Barailler</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Charles, Sophie" sort="Charles, Sophie" uniqKey="Charles S" first="Sophie" last="Charles">Sophie Charles</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Goutorbe, Felix" sort="Goutorbe, Felix" uniqKey="Goutorbe F" first="Felix" last="Goutorbe">Felix Goutorbe</name><affiliation><nlm:aff id="aff2">Department of Gastroenterology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author><author><name sortKey="Devaux, Suzanne" sort="Devaux, Suzanne" uniqKey="Devaux S" first="Suzanne" last="Devaux">Suzanne Devaux</name><affiliation><nlm:aff id="aff1">Department of Dermatology, Hôpital Côte Basque, Bayonne, France</nlm:aff></affiliation></author></analytic><series><title level="j">JAAD Case Reports</title><idno type="eISSN">2352-5126</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sato, S" uniqKey="Sato S">S. Sato</name></author><author><name sortKey="Hirakata, M" uniqKey="Hirakata M">M. Hirakata</name></author><author><name sortKey="Kuwana, M" uniqKey="Kuwana M">M. Kuwana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moghadam Kia, S" uniqKey="Moghadam Kia S">S. Moghadam-Kia</name></author><author><name sortKey="Oddis, C V" uniqKey="Oddis C">C.V. Oddis</name></author><author><name sortKey="Sato, S" uniqKey="Sato S">S. Sato</name></author><author><name sortKey="Kuwana, M" uniqKey="Kuwana M">M. Kuwana</name></author><author><name sortKey="Aggarwal, R" uniqKey="Aggarwal R">R. Aggarwal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujimoto, M" uniqKey="Fujimoto M">M. Fujimoto</name></author><author><name sortKey="Watanabe, R" uniqKey="Watanabe R">R. Watanabe</name></author><author><name sortKey="Ishitsuka, Y" uniqKey="Ishitsuka Y">Y. Ishitsuka</name></author><author><name sortKey="Okiyama, N" uniqKey="Okiyama N">N. Okiyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fiorentino, D" uniqKey="Fiorentino D">D. Fiorentino</name></author><author><name sortKey="Chung, L" uniqKey="Chung L">L. Chung</name></author><author><name sortKey="Zwerner, J" uniqKey="Zwerner J">J. Zwerner</name></author><author><name sortKey="Rosen, A" uniqKey="Rosen A">A. Rosen</name></author><author><name sortKey="Casciola Rosen, L" uniqKey="Casciola Rosen L">L. Casciola-Rosen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurtzman, D J B" uniqKey="Kurtzman D">D.J.B. Kurtzman</name></author><author><name sortKey="Vleugels, R A" uniqKey="Vleugels R">R.A. Vleugels</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clottu, A" uniqKey="Clottu A">A. Clottu</name></author><author><name sortKey="Laffitte, E" uniqKey="Laffitte E">E. Laffitte</name></author><author><name sortKey="Prins, C" uniqKey="Prins C">C. Prins</name></author><author><name sortKey="Chizzolini, C" uniqKey="Chizzolini C">C. Chizzolini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Charbit, L" uniqKey="Charbit L">L. Charbit</name></author><author><name sortKey="Bursztejn, A C" uniqKey="Bursztejn A">A.C. Bursztejn</name></author><author><name sortKey="Mohamed, S" uniqKey="Mohamed S">S. Mohamed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narang, N S" uniqKey="Narang N">N.S. Narang</name></author><author><name sortKey="Casciola Rosen, L" uniqKey="Casciola Rosen L">L. Casciola-Rosen</name></author><author><name sortKey="Li, S" uniqKey="Li S">S. Li</name></author><author><name sortKey="Chung, L" uniqKey="Chung L">L. Chung</name></author><author><name sortKey="Fiorentino, D F" uniqKey="Fiorentino D">D.F. Fiorentino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamaoka, T" uniqKey="Yamaoka T">T. Yamaoka</name></author><author><name sortKey="Doi, C" uniqKey="Doi C">C. Doi</name></author><author><name sortKey="Yokomi, A" uniqKey="Yokomi A">A. Yokomi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="case-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">JAAD Case Rep</journal-id><journal-id journal-id-type="iso-abbrev">JAAD Case Rep</journal-id><journal-title-group><journal-title>JAAD Case Reports</journal-title></journal-title-group><issn pub-type="epub">2352-5126</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31008175</article-id><article-id pub-id-type="pmc">6454120</article-id><article-id pub-id-type="publisher-id">S2352-5126(19)30074-8</article-id><article-id pub-id-type="doi">10.1016/j.jdcr.2019.02.019</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group></article-categories><title-group><article-title>An unusual anti–melanoma differentiation–associated protein 5 amyopathic dermatomyositis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Barailler</surname><given-names>Héloïse</given-names></name><degrees>MD</degrees><email>heloise.barailler@gmail.com</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author"><name><surname>Charles</surname><given-names>Sophie</given-names></name><degrees>MD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Goutorbe</surname><given-names>Felix</given-names></name><degrees>MD</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Devaux</surname><given-names>Suzanne</given-names></name><degrees>MD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Dermatology, Hôpital Côte Basque, Bayonne, France</aff><aff id="aff2"><label>b</label>Department of Gastroenterology, Hôpital Côte Basque, Bayonne, France</aff><author-notes><corresp id="cor1"><label>∗</label>Correspondence to: Héloïse Barailler, MD, Centre Hospitalier de la Côte Basque, 13, avenue de l'interne Jacques Loeb, 64100 Bayonne, France. <email>heloise.barailler@gmail.com</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>06</day><month>4</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><month>4</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>06</day><month>4</month><year>2019</year></pub-date><volume>5</volume><issue>4</issue><fpage>383</fpage><lpage>385</lpage><permissions><copyright-statement>© 2019 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>American Academy of Dermatology, Inc.</copyright-holder><license license-type="CC BY-NC-ND" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).</license-p></license></permissions><kwd-group id="kwrds0010"><title>Key words</title><kwd>anti–melanoma differentiation-associated protein 5</kwd><kwd>dermatomyositis</kwd><kwd>digital necrosis</kwd><kwd>paraneoplastic</kwd></kwd-group><kwd-group id="kwrds0015"><title>Abbreviations used</title><kwd>CADM, clinically amyopathic dermatomyositis</kwd><kwd>CT, computed tomography</kwd><kwd>DM, dermatomyositis</kwd><kwd>MSA, myositis-specific antibodies</kwd><kwd>MDA-5, melanoma differentiation–associated protein 5</kwd></kwd-group></article-meta></front><body><sec id="sec1"><title>Introduction</title><p id="p0010">Dermatomyositis (DM), an inflammatory autoimmune disorder characterized by cutaneous manifestations and muscle involvement, is now well described with different myositis-specific antibodies (MSA), leading to specific therapeutic approaches according to the antibody type found. Melanoma differentiation–associated protein 5 (MDA-5), a new specific antibody, was first described by Sato et al in 2005,<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> mostly in the Asian population. It has been frequently associated with clinically amyopathic dermatomyositis (CADM). Previous studies found that anti–MDA-5 antibodies are associated with a rapidly progressive interstitial lung disease (ILD)<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> leading to a poor prognosis. Patients with anti–MDA-5 also present with characteristic skin features: Gottron papules, livedo, skin ulceration, and necrosis. Here we report an unusual case of anti–MDA-5 dermatomyositis without ILD occurring in a paraneoplastic context.</p></sec><sec id="sec2"><title>Observation</title><p id="p0015">A 70-year-old white man was treated with sorafenib for nonmetastatic hepatocellular carcinoma starting in May 2017. Before introduction of this treatment, he already presented with painful cutaneous ulcers of both hands. Angio–computed tomography (CT) scan of both arms found no anomaly. Physical examination found facial erythema, painful digital cyanosis and ulcers, and erythematous and violaceous papules on the back of hands and fingers with necrotic paronychia (<xref rid="fig1" ref-type="fig">Fig 1</xref>).<fig id="fig1"><label>Fig 1</label><caption><p>Acrocyanosis, painful erythematous and violaceous papules on the back of hands and fingers and necrotic paronychia.</p></caption><graphic xlink:href="gr1"></graphic></fig></p><p id="p0020">The patient also had erythematous lesions on both elbows. There was no myalgia or dyspnea and lung auscultation was clear. Blood test found normal creatine phosphokinase level and normal coagulation parameters. Immunologic explorations found positive antinuclear antibodies (1/640), with the presence of anti–MDA-5 antibodies. Anti-scl70, anticentromere, anti-RNP, anti-Ro52, and anti-TIF1γ were negative. Results of vascular tests including angio-CT scan, arterial echography, and capillaroscopy were normal. Echocardiography found no anomaly. Positron emission tomography found hyperfixation of the hepatic carcinoma without additional extrahepatic fixation. Muscular magnetic resonance imaging and electromyography did not find any specific characteristics of polymyositis. Thoracic CT scan and spirometry found a restrictive lung disease caused by active smoking but no images of ILD. Cutaneous biopsy of a papular lesion on the hand found a lichenoid reaction with mild lymphocytic infiltration without vasculitis (<xref rid="fig2" ref-type="fig">Fig 2</xref>). Direct immunofluorescence test was positive, with perivascular IgG, IgA, and C3 deposits.<fig id="fig2"><label>Fig 2</label><caption><p>Cutaneous biopsy shows lichenoid reaction with mild lymphocytic infiltration without vasculitis. (Hematoxylin-eosin stain; original magnification: ×200.)</p></caption><graphic xlink:href="gr2"></graphic></fig></p><p id="p0025">On admission, intravenous vasodilator perfusions (iloprost) and antiplatelet drug were initiated. Then, with severe cutaneous necrotic anti–MDA-5 amyopathic dermatomyositis diagnosed, high doses of intravenous corticotherapy (1 mg/kg/d) and immunoglobulin perfusions (2 g/kg every 4 weeks) were started. We did not diagnose Buerger disease based on the clinical presentation and the positivity of anti–MDA-5 antibodies. Hydroxychloroquine was added 1 month later, because he was refractory to standard immunosuppressive treatment with extension of cutaneous necrotic features (<xref rid="fig3" ref-type="fig">Fig 3</xref>).<fig id="fig3"><label>Fig 3</label><caption><p><bold>A</bold> and <bold>B,</bold> Necrotic evolution of cutaneous ulcers with spontaneous amputations of the fingers.</p></caption><graphic xlink:href="gr3"></graphic></fig></p><p id="p0030">A preventive surgery for finger necrosis was performed. Despite this treatment, cutaneous lesions kept progressing, with extension of necrosis and spontaneous amputation. Considering the severity of the disease, we started plasmapheresis and rituximab infusions. Symptomatic treatment was optimized, adding nifedipine and curative anticoagulant therapy by enoxaparine. Unfortunately, skin involvement worsened under maximum-tolerated treatment dose. Four months after the diagnosis, our patient ultimately died from hepatocarcinoma progression.</p></sec><sec id="sec3"><title>Discussion</title><p id="p0035">We present an original case of severe cutaneous digital necrosis in a context of amyopathic paraneoplastic dermatomyositis with anti–MDA-5 antibodies without ILD.</p><p id="p0040">Dermatomyositis management is influenced by the presence of a specific type of MSA, since the clinical spectrum of this disease is heterogeneous.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Detection of MSA can be useful for prognosis and therapeutic options, even if treatment is truly guided by patient presentation and co-morbidities. Usually, detection of anti-MDA-5 is known to be associated with a poor prognosis due to rapidly progressive ILD.</p><p id="p0045">Recently, studies showed that anti–MDA-5 antibodies were associated with a specific cutaneous phenotype like severe skin ulcerations and painful palmar papules.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Skin ulcerations are preferentially located on lateral nailfolds, Gottron papules, and elbows. There is also an increased risk of oral ulceration, hand swelling, and hair loss. Our patient had a neoplastic disease and presented with a typically severe cutaneous involvement, but interestingly had no ILD. No pulmonary involvement was detected during follow-up with imaging and spirometry. Early initiation of immunosuppressive therapy might have helped to prevent interstitial lung involvement.</p><p id="p0050">Treatment of anti–MDA-5 dermatomyositis is not well established. High doses of corticosteroids is the first-line treatment and should be started as soon as possible. Immunosuppressive treatment must be considered early after the onset of the disease, as anti–MDA-5 antibodies are usually associated with severe pulmonary involvement. A collaborative discussion is needed for each patient, as there are no official guidelines to follow for CADM treatment. In our case, we proceeded to a step-by-step treatment intensification. We think that anti–MDA-5 DM treatment should be guided by severity of the disease at presentation and undoubtedly if extracutaneous involvement is present.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref></p><p id="p0055">Rapidly cutaneous necrosis of fingers with spontaneous amputation has already been described but in most cases were associated with ILD.<xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib7" ref-type="bibr">7</xref>, <xref rid="bib8" ref-type="bibr">8</xref> Consistently, a recent retrospective study showed that there was a strong association between cutaneous ulcers and risk of ILD.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> The first case of anti–MDA-5 DM described in Western Europe presented with a cutaneous necrosis, but pulmonary involvement was diagnosed. Prednisone, high-dose intravenous immunoglobulin, cyclophosphamide, mycophenolate mofetil, iloprost, and rituximab, managed to stabilize the disease.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Another patient with spontaneous amputation of the fingers also had ILD and was treated by corticosteroids, cyclophosphamide, intravenous immunoglobulin, and cyclosporine with a relative efficacy on the lungs but progression of cutaneous necrosis.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref></p><p id="p0060">To our knowledge, this is the only case of rapidly extensive digital necrosis caused by anti–MDA-5 dermatomyositis in a paraneoplastic context. Actually, frequent MSA associated with cancer are anti-TIF1γ and anti-NXP2 antibodies. Neoplastic diseases are found in only 20% of dermatomyositis with anti–MDA-5.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> To date, only few cases have been reported.<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> When occurring in a paraneoplastic context, treating DM with conventional therapy can be challenging because immunosuppressive therapy can lead to the spread of cancer. This was what probably caused patient death in our case. Surgical amputation can be considered sometimes to prevent infectious complications and discomfort. However, surgery does not stop necrosis from spreading afterward.</p><p id="p0065">Our case highlights the clinical heterogeneity of CADM. It is, to our knowledge, the first case of paraneoplastic amyopathic anti–MDA-5 dermatomyositis without lung involvement. 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