Systemic sclerosis with malignant acanthosis nigricans in a patient with gastric adenocarcinoma
Identifieur interne : 000312 ( Pmc/Corpus ); précédent : 000311; suivant : 000313Systemic sclerosis with malignant acanthosis nigricans in a patient with gastric adenocarcinoma
Auteurs : Daniel A. Nadelman ; David Orbuch ; Sabina Sandigursky ; Alisa N. FemiaSource :
- JAAD Case Reports [ 2352-5126 ] ; 2019.
Url:
DOI: 10.1016/j.jdcr.2019.10.003
PubMed: 31768409
PubMed Central: 6872833
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Systemic sclerosis with malignant acanthosis nigricans in a patient with gastric adenocarcinoma</title><author><name sortKey="Nadelman, Daniel A" sort="Nadelman, Daniel A" uniqKey="Nadelman D" first="Daniel A." last="Nadelman">Daniel A. Nadelman</name><affiliation><nlm:aff id="aff1">Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan</nlm:aff></affiliation></author><author><name sortKey="Orbuch, David" sort="Orbuch, David" uniqKey="Orbuch D" first="David" last="Orbuch">David Orbuch</name><affiliation><nlm:aff id="aff2">Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Sandigursky, Sabina" sort="Sandigursky, Sabina" uniqKey="Sandigursky S" first="Sabina" last="Sandigursky">Sabina Sandigursky</name><affiliation><nlm:aff id="aff3">Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Femia, Alisa N" sort="Femia, Alisa N" uniqKey="Femia A" first="Alisa N." last="Femia">Alisa N. Femia</name><affiliation><nlm:aff id="aff2">Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31768409</idno><idno type="pmc">6872833</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872833</idno><idno type="RBID">PMC:6872833</idno><idno type="doi">10.1016/j.jdcr.2019.10.003</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000312</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000312</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Systemic sclerosis with malignant acanthosis nigricans in a patient with gastric adenocarcinoma</title><author><name sortKey="Nadelman, Daniel A" sort="Nadelman, Daniel A" uniqKey="Nadelman D" first="Daniel A." last="Nadelman">Daniel A. Nadelman</name><affiliation><nlm:aff id="aff1">Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan</nlm:aff></affiliation></author><author><name sortKey="Orbuch, David" sort="Orbuch, David" uniqKey="Orbuch D" first="David" last="Orbuch">David Orbuch</name><affiliation><nlm:aff id="aff2">Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Sandigursky, Sabina" sort="Sandigursky, Sabina" uniqKey="Sandigursky S" first="Sabina" last="Sandigursky">Sabina Sandigursky</name><affiliation><nlm:aff id="aff3">Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, New York</nlm:aff></affiliation></author><author><name sortKey="Femia, Alisa N" sort="Femia, Alisa N" uniqKey="Femia A" first="Alisa N." last="Femia">Alisa N. Femia</name><affiliation><nlm:aff id="aff2">Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York</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="Shah, A A" uniqKey="Shah A">A.A. Shah</name></author><author><name sortKey="Hummers, L K" uniqKey="Hummers L">L.K. Hummers</name></author><author><name sortKey="Casciola Rosen, L" uniqKey="Casciola Rosen L">L. Casciola-Rosen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shah, A A" uniqKey="Shah A">A.A. Shah</name></author><author><name sortKey="Rosen, L C" uniqKey="Rosen L">L.C. Rosen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baijens, L W" uniqKey="Baijens L">L.W. Baijens</name></author><author><name sortKey="Manni, J J" uniqKey="Manni J">J.J. Manni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samotij, D" uniqKey="Samotij D">D. Samotij</name></author><author><name sortKey="Maj, J" uniqKey="Maj J">J. Maj</name></author><author><name sortKey="Reich, A" uniqKey="Reich A">A. Reich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Q" uniqKey="Yu Q">Q. Yu</name></author><author><name sortKey="Li, X L" uniqKey="Li X">X.L. Li</name></author><author><name sortKey="Ji, G" uniqKey="Ji G">G. Ji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Onishi, A" uniqKey="Onishi A">A. Onishi</name></author><author><name sortKey="Sugiyama, D" uniqKey="Sugiyama D">D. Sugiyama</name></author><author><name sortKey="Kumagai, S" uniqKey="Kumagai S">S. Kumagai</name></author><author><name sortKey="Morinobu, A" uniqKey="Morinobu A">A. Morinobu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shah, A A" uniqKey="Shah A">A.A. Shah</name></author><author><name sortKey="Xu, G" uniqKey="Xu G">G. Xu</name></author><author><name sortKey="Rosen, A" uniqKey="Rosen A">A. Rosen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saif, M W" uniqKey="Saif M">M.W. Saif</name></author><author><name sortKey="Agarwal, A" uniqKey="Agarwal A">A. Agarwal</name></author><author><name sortKey="Hellinger, J" uniqKey="Hellinger J">J. Hellinger</name></author><author><name sortKey="Park, D J" uniqKey="Park D">D.J. Park</name></author><author><name sortKey="Volkmann, E" uniqKey="Volkmann E">E. Volkmann</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">31768409</article-id><article-id pub-id-type="pmc">6872833</article-id><article-id pub-id-type="publisher-id">S2352-5126(19)30613-7</article-id><article-id pub-id-type="doi">10.1016/j.jdcr.2019.10.003</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Report</subject></subj-group></article-categories><title-group><article-title>Systemic sclerosis with malignant acanthosis nigricans in a patient with gastric adenocarcinoma</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Nadelman</surname><given-names>Daniel A.</given-names></name><degrees>BA</degrees><email>dnadelma@med.umich.edu</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Orbuch</surname><given-names>David</given-names></name><degrees>MD</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Sandigursky</surname><given-names>Sabina</given-names></name><degrees>MD</degrees><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Femia</surname><given-names>Alisa N.</given-names></name><degrees>MD</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan</aff><aff id="aff2"><label>b</label>Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York</aff><aff id="aff3"><label>c</label>Division of Rheumatology, Department of Medicine, New York University School of Medicine, New York, New York</aff><author-notes><corresp id="cor1"><label>∗</label>Correspondence to: Daniel A. Nadelman, BA, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI, 48109. <email>dnadelma@med.umich.edu</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>20</day><month>11</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>12</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>20</day><month>11</month><year>2019</year></pub-date><volume>5</volume><issue>12</issue><fpage>1045</fpage><lpage>1047</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>acanthosis nigricans</kwd><kwd>gastric cancer</kwd><kwd>paraneoplastic</kwd><kwd>systemic sclerosis</kwd></kwd-group><kwd-group id="kwrds0015"><title>Abbreviation used</title><kwd>SSc, systemic sclerosis</kwd></kwd-group></article-meta></front><body><sec id="sec1"><title>Introduction</title><p id="p0010">Systemic sclerosis (SSc) is an idiopathic sclerosing condition that may affect both the skin and internal organs.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Although SSc has been associated with an increase in the development of malignant neoplasms, the disease can present in a paraneoplastic manner months to years after initial cancer diagnosis in rare cases.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref><sup>,</sup><xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> Malignant acanthosis nigricans is a rare paraneoplastic skin syndrome that presents with sudden onset of hyperpigmented velvety plaques, most commonly in intertriginous areas. Here, we report a case of newly acquired SSc and acanthosis nigricans in a patient with a 2-year history of gastric adenocarcinoma being treated with capecitabine.</p></sec><sec id="sec2"><title>Case report</title><p id="p0015">A 34-year-old woman with a 6-year history of metastatic gastric adenocarcinoma presented with 2 months of abrupt-onset Raynaud phenomenon, fingertip ulcerations, stiffness in the joints of her hands, lethargy, and shortness of breath. The patient had been receiving capecitabine chemotherapy for 2 years before the onset of symptoms. Before this, she had been treated with 5-fluorouracil, oxaliplatin, epirubicin, and doxorubicin. Her cancer was responding moderately well to capecitabine. On examination, healing erosions of the finger tips (<xref rid="fig1" ref-type="fig">Fig 1</xref>, <italic>A</italic>), capillary dropout (<xref rid="fig1" ref-type="fig">Fig 1</xref>, <italic>B</italic>), and cutaneous sclerosis with pigmentary changes were present. Mild sclerodactyly extended to the metacarpophalangeal joints (<xref rid="fig2" ref-type="fig">Fig 2</xref>). Hyperpigmented velvety plaques of the posterior neck, axillae, malar cheeks, forearms, and palms (<xref rid="fig3" ref-type="fig">Fig 3</xref>) consistent with acanthosis nigricans were present.<fig id="fig1"><label>Fig 1</label><caption><p><bold>A</bold>, Healing erosions of the fingertips and (<bold>B</bold>) capillary dropout.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Fig 2</label><caption><p>Mild sclerodactyly.</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Fig 3</label><caption><p>Hyperpigmented velvety plaques consistent with acanthosis nigricans.</p></caption><graphic xlink:href="gr3"></graphic></fig></p><p id="p0020">Laboratory testing results were notable for an elevated anti-RNA polymerase III of 59 units (normal, <20 units) and an antinuclear antibody of 1:640 in a speckled pattern. Results of other tests, including anti-SSa, anti-SSb, aldolase, myositis panel, C-reactive protein, anti-Scl 70, and anti-centromere, were unremarkable. Basic blood test results were unremarkable other than a hemoglobin level of 9.4 g/dL. The patient declined pulmonary function testing and chest imaging to evaluate for interstitial lung disease. An echocardiogram was unremarkable.</p><p id="p0025">The patient met criteria for SSc based on 2013 European League Against Rheumatism/American College of Rheumatology scoring, which incorporates skin thickening, Raynaud phenomenon with fingertip ulcerations or scars, cutaneous telangiectasias, nailfold capillary changes, and presence of autoantibodies relevant to SSc. Hydroxychloroquine therapy was initiated and resulted in improvement of her shortness of breath and fatigue, and nifedipine reduced the frequency of Raynaud phenomenon symptoms and resulted in healing of associated erosions and ulcerations. The patient continued receiving capecitabine chemotherapy for her gastric adenocarcinoma without significant progression of the cancer.</p></sec><sec id="sec3"><title>Discussion</title><p id="p0030">Paraneoplastic syndromes are characterized as symptoms occurring in patients with cancer that are not directly related to tumor invasion or metastases. The precise mechanisms involved in the development of paraneoplastic syndromes are unknown, although it has been suggested that ectopic hormone production and cancer-induced autoimmunity play a role.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref><sup>,</sup><xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> It is estimated that 7% of patients with cancer experience paraneoplastic phenomena.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> Paraneoplastic syndromes may exhibit a variety of clinical manifestations, including endocrine, neurologic, and rheumatologic symptoms.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref><sup>,</sup><xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Acanthosis nigricans may result as a paraneoplastic phenomenon in a number of different cancers; in these situations, unusual body surface areas may be affected, and the term <italic>malignant acanthosis nigricans</italic> is applied. Malignant acanthosis nigricans is particularly likely to occur in patients with gastric adenocarcinoma, as in the case of our patient.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref></p><p id="p0035">Although polymyositis and dermatomyositis are more common rheumatologic disorders of paraneoplastic origin, SSc may also develop as a paraneoplastic phenomenon.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Acute onset of SSc symptoms with rapid progression, as occurred in our patient, should raise suspicion for the possibility of a paraneoplastic etiology.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref><sup>,</sup><xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> The presence of RNA polymerase III autoantibodies is also consistent with paraneoplastic SSc; recent reports have shown a close association between RNA polymerase III autoantibodies and SSc in the setting of malignancy.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref> This association is significant; in fact, patients with RNA polymerase III-positive SSc have been shown to be 5 times more likely to have an underlying neoplasm.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> It has been suggested that RNA polymerase antigens are overexpressed in neoplastic cells, which, in turn, stimulates an immune response resulting in the formation of anti-RNA polymerase III antibodies.</p><p id="p0040">Sudden onset and rapid progression of clinical symptoms is also characteristic of paraneoplastic, as opposed to idiopathic SSc. Anti-centromere and anti-Scl 70 antibodies, although typically elevated in idiopathic SSc, are notably absent in many paraneoplastic cases.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref></p><p id="p0045">Although several chemotherapeutic agents, including paclitaxel, bleomycin, and doxorubicin, have been implicated in the development of SSc, drug-induced SSc has not been shown to be associated with elevated RNA polymerase III autoantibodies as in the case of paraneoplastic SSc. Several case reports describe scleroderma-like changes in the setting of capecitabine chemotherapy, yet again, none of these cases showed positive RNA polymerase III autoantibodies.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> It therefore seems unlikely that SSc in our patient was induced by chemotherapy.</p><p id="p0050">Paraneoplastic SSc with positive RNA polymerase III autoantibodies has been described in the setting of hematologic malignancies and colorectal, lung, pancreatic, and solid breast tumors.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref><sup>,</sup><xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> However, to the best of our knowledge, this patient is the first reported case of paraneoplastic SSc in the setting of gastric cancer. 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