Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">New-onset autoantibody-mediated nephritis during ustekinumab therapy for psoriasis in patients with and without prior systemic lupus erythematosus</title><author><name sortKey="Al Khalili, Ayida" sort="Al Khalili, Ayida" uniqKey="Al Khalili A" first="Ayida" last="Al Khalili">Ayida Al Khalili</name><affiliation><nlm:aff id="aff1">Dermatology Unit, Sultan Qaboos University Hospital, Sultanate of Oman</nlm:aff></affiliation></author><author><name sortKey="Scott, Leah" sort="Scott, Leah" uniqKey="Scott L" first="Leah" last="Scott">Leah Scott</name><affiliation><nlm:aff id="aff2">Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada</nlm:aff></affiliation></author><author><name sortKey="Dutz, Jan P" sort="Dutz, Jan P" uniqKey="Dutz J" first="Jan P." last="Dutz">Jan P. Dutz</name><affiliation><nlm:aff id="aff2">Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31417952</idno><idno type="pmc">6690636</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690636</idno><idno type="RBID">PMC:6690636</idno><idno type="doi">10.1016/j.jdcr.2019.05.022</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000309</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000309</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">New-onset autoantibody-mediated nephritis during ustekinumab therapy for psoriasis in patients with and without prior systemic lupus erythematosus</title><author><name sortKey="Al Khalili, Ayida" sort="Al Khalili, Ayida" uniqKey="Al Khalili A" first="Ayida" last="Al Khalili">Ayida Al Khalili</name><affiliation><nlm:aff id="aff1">Dermatology Unit, Sultan Qaboos University Hospital, Sultanate of Oman</nlm:aff></affiliation></author><author><name sortKey="Scott, Leah" sort="Scott, Leah" uniqKey="Scott L" first="Leah" last="Scott">Leah Scott</name><affiliation><nlm:aff id="aff2">Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada</nlm:aff></affiliation></author><author><name sortKey="Dutz, Jan P" sort="Dutz, Jan P" uniqKey="Dutz J" first="Jan P." last="Dutz">Jan P. Dutz</name><affiliation><nlm:aff id="aff2">Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada</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="Tselios, K" uniqKey="Tselios K">K. Tselios</name></author><author><name sortKey="Yap, K S" uniqKey="Yap K">K.S. Yap</name></author><author><name sortKey="Pakchotanon, R" uniqKey="Pakchotanon R">R. Pakchotanon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Millns, J L" uniqKey="Millns J">J.L. Millns</name></author><author><name sortKey="Muller, S A" uniqKey="Muller S">S.A. Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zalla, M J" uniqKey="Zalla M">M.J. Zalla</name></author><author><name sortKey="Muller, S A" uniqKey="Muller S">S.A. Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Souza, A" uniqKey="De Souza A">A. De Souza</name></author><author><name sortKey="Ali Shaw, T" uniqKey="Ali Shaw T">T. Ali-Shaw</name></author><author><name sortKey="Strober, B E" uniqKey="Strober B">B.E. Strober</name></author><author><name sortKey="Franks, A G" uniqKey="Franks A">A.G. Franks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Winchester, D" uniqKey="Winchester D">D. Winchester</name></author><author><name sortKey="Duffin, K C" uniqKey="Duffin K">K.C. Duffin</name></author><author><name sortKey="Hansen, C" uniqKey="Hansen C">C. Hansen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varada, S" uniqKey="Varada S">S. Varada</name></author><author><name sortKey="Gottlieb, A B" uniqKey="Gottlieb A">A.B. Gottlieb</name></author><author><name sortKey="Merola, J F" uniqKey="Merola J">J.F. Merola</name></author><author><name sortKey="Saraiya, A R" uniqKey="Saraiya A">A.R. Saraiya</name></author><author><name sortKey="Tintle, S J" uniqKey="Tintle S">S.J. Tintle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Vollenhoven, R F" uniqKey="Van Vollenhoven R">R.F. van Vollenhoven</name></author><author><name sortKey="Hahn, B H" uniqKey="Hahn B">B.H. Hahn</name></author><author><name sortKey="Tsokos, G C" uniqKey="Tsokos G">G.C. Tsokos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macarthur, K M" uniqKey="Macarthur K">K.M. MacArthur</name></author><author><name sortKey="Merkel, P A" uniqKey="Merkel P">P.A. Merkel</name></author><author><name sortKey="Van Voorhees, A S" uniqKey="Van Voorhees A">A.S. Van Voorhees</name></author><author><name sortKey="Nguyen, J" uniqKey="Nguyen J">J. Nguyen</name></author><author><name sortKey="Rosenbach, M" uniqKey="Rosenbach M">M. Rosenbach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le Guern, A" uniqKey="Le Guern A">A. Le Guern</name></author><author><name sortKey="Alkeraye, S" uniqKey="Alkeraye S">S. Alkeraye</name></author><author><name sortKey="Vermersch Langlin, A" uniqKey="Vermersch Langlin A">A. Vermersch-Langlin</name></author><author><name sortKey="Coupe, P" uniqKey="Coupe P">P. Coupe</name></author><author><name sortKey="Vonarx, M" uniqKey="Vonarx M">M. Vonarx</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakayama, C" uniqKey="Nakayama C">C. Nakayama</name></author><author><name sortKey="Fujita, Y" uniqKey="Fujita Y">Y. Fujita</name></author><author><name sortKey="Watanabe, M" uniqKey="Watanabe M">M. Watanabe</name></author><author><name sortKey="Shimizu, H" uniqKey="Shimizu H">H. Shimizu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Onsun, N" uniqKey="Onsun N">N. Onsun</name></author><author><name sortKey="Sallahoglu, K" uniqKey="Sallahoglu K">K. Sallahoglu</name></author><author><name sortKey="Dizman, D" uniqKey="Dizman D">D. Dizman</name></author><author><name sortKey="Su, O" uniqKey="Su O">O. Su</name></author><author><name sortKey="Tosuner, Z" uniqKey="Tosuner Z">Z. Tosuner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, J G" uniqKey="Becker J">J.G. Becker</name></author><author><name sortKey="Mundi, J P" uniqKey="Mundi J">J.P. Mundi</name></author><author><name sortKey="Newlove, T" uniqKey="Newlove T">T. Newlove</name></author><author><name sortKey="Mones, J" uniqKey="Mones J">J. Mones</name></author><author><name sortKey="Shupack, J" uniqKey="Shupack J">J. Shupack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, T F" uniqKey="Liu T">T.F. Liu</name></author><author><name sortKey="Jones, B M" uniqKey="Jones B">B.M. Jones</name></author><author><name sortKey="Wong, R W" uniqKey="Wong R">R.W. Wong</name></author><author><name sortKey="Srivastava, G" uniqKey="Srivastava G">G. Srivastava</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rodriguez Jimenez, P" uniqKey="Rodriguez Jimenez P">P. Rodriguez-Jimenez</name></author><author><name sortKey="Chicharro, P" uniqKey="Chicharro P">P. Chicharro</name></author><author><name sortKey="Godoy, A" uniqKey="Godoy A">A. Godoy</name></author><author><name sortKey="Llamas Velasco, M" uniqKey="Llamas Velasco M">M. Llamas-Velasco</name></author><author><name sortKey="Garcia, M" uniqKey="Garcia M">M. Garcia</name></author><author><name sortKey="Dauden, E" uniqKey="Dauden E">E. Dauden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steri, M" uniqKey="Steri M">M. Steri</name></author><author><name sortKey="Orru, V" uniqKey="Orru V">V. Orru</name></author><author><name sortKey="Idda, M L" uniqKey="Idda M">M.L. Idda</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">31417952</article-id><article-id pub-id-type="pmc">6690636</article-id><article-id pub-id-type="publisher-id">S2352-5126(19)30210-3</article-id><article-id pub-id-type="doi">10.1016/j.jdcr.2019.05.022</article-id><article-categories><subj-group subj-group-type="heading"><subject>Case Series</subject></subj-group></article-categories><title-group><article-title>New-onset autoantibody-mediated nephritis during ustekinumab therapy for psoriasis in patients with and without prior systemic lupus erythematosus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Al Khalili</surname><given-names>Ayida</given-names></name><degrees>MD, FRCPC</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Scott</surname><given-names>Leah</given-names></name><degrees>MD, FRCPC</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Dutz</surname><given-names>Jan P.</given-names></name><degrees>MD, FRCPC</degrees><email>jan.dutz@vch.ca</email><xref rid="aff2" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Dermatology Unit, Sultan Qaboos University Hospital, Sultanate of Oman</aff><aff id="aff2"><label>b</label>Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada</aff><author-notes><corresp id="cor1"><label>∗</label>Correspondence to: Jan P. Dutz, MD, FRCPC, Professor and Head, Department of Dermatology and Skin Science, University of British Columbia, 835 West Tenth Avenue, Vancouver, BC V5Z 4E8, Canada. <email>jan.dutz@vch.ca</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>02</day><month>8</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>8</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>02</day><month>8</month><year>2019</year></pub-date><volume>5</volume><issue>8</issue><fpage>682</fpage><lpage>685</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>adverse event</kwd><kwd>nephritis</kwd><kwd>psoriasis</kwd><kwd>psoriatic arthritis</kwd><kwd>systemic lupus erythematosus</kwd><kwd>ustekinumab</kwd><kwd>vasculitis</kwd></kwd-group><kwd-group id="kwrds0015"><title>Abbreviations used</title><kwd>ANA, anti-nuclear antibody</kwd><kwd>BAFF, B-cell–activating factor of the tumor necrosis factor family</kwd><kwd>IL, interleukin</kwd><kwd>LE, lupus erythematosus</kwd><kwd>PASI, psoriasis activity and severity index</kwd><kwd>PsA, psoriatic arthritis</kwd><kwd>SLE, systemic lupus erythematosus</kwd></kwd-group></article-meta></front><body><sec id="sec1"><title>Introduction</title><p id="p0010">Psoriasis and lupus erythematosus (LE) are autoimmune diseases that affect the skin. Patients with these diseases may share a similar genetic predisposition, as genome-wide association studies have identified common genetic polymorphisms. Yet, the coexistence of these diseases is uncommon, an observation previously thought to be owing to the T helper (Th)2 immune predominance in systemic lupus erythematosus (SLE) in contra-distinction to the Th1 immune predominance in psoriasis. A review of more than 1800 SLE patients at the Toronto Lupus Clinic found that the incidence of psoriasis is increased in this population compared with the general population (estimated at 3.89% in their cohort compared with 1.6% in the Canadian population).<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Patients with concurrent SLE and psoriasis may have unusual photosensitive psoriasis with the initial presentation of psoriasis lesions on the sun-exposed extremities.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref></p><p id="p0015">The treatment of psoriasis in patients with SLE can be problematic. Phototherapy is generally avoided. Antimalarial medications such as hydroxychloroquine and chloroquine may induce photosensitivity and psoriasis, although this notion has been mostly based on case reports and small series. Ustekinumab, a monoclonal antibody to the p40 subunits of the interleukin (IL)-12 and IL-23 receptors, is a safe and efficacious treatment for psoriasis and has been used anecdotally to treat subacute cutaneous LE<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> and hypertrophic LE.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Ustekinumab has shown possible efficacy in cutaneous LE when used to treat 5 patients with coexisting psoriasis and LE.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Ustekinumab has recently been studied as a treatment for SLE in a phase 2 study of 102 adults showing improvement in musculoskeletal and cutaneous disease activity at 24 weeks.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref></p><p id="p0020">Here we report on 3 patients treated with ustekinumab for psoriasis. Two patients with prior SLE had new-onset lupus nephritis while on ustekinumab. A third individual had probable SLE with vasculitis and nephritis while on ustekinumab. This case series highlights similarities in clinical presentation suggesting a common mechanism.</p></sec><sec id="sec2"><title>Case reports</title><sec id="sec2.1"><title>Case 1</title><p id="p0025">A woman in her 30s presented with hemolytic anemia and thrombocytopenia, malar rash, photosensitivity, oral ulcers, and pericarditis. SLE was the diagnosis. Treatment included plasmapheresis, high-dose prednisone, azathioprine, and hydroxychloroquine. One year later, biopsy-proven psoriasis developed. Multiple therapies including methotrexate, acitretin, and antimalarial withdrawal failed to improve her skin condition (<xref rid="fig1" ref-type="fig">Fig 1</xref>). Her psoriasis worsened over 6 years. She was started on ustekinumab (45 mg every 12 weeks). This treatment improved her skin condition at 4 months (Psoriasis Activity and Severity Index [PASI], 13.3 to 1.8). Anti–double-stranded DNA antibodies developed shortly after the initiation of ustekinumab. She presented 6 months later with increasing fatigue, vasculitis, and vasculopathic skin lesions on both palms and proximal nail fold, increasing anti–double-stranded DNA, and hypocomplementemia. This condition was treated as a lupus flare with intravenous methylprednisone followed by prednisone. Twenty months after ustekinumab initiation, she had worsening fatigue, bilateral pleural effusions, pancytopenia, and increased inflammatory markers. Prednisone and azathioprine dosage were increased. Scaly plaques to both palms were noted with histopathology consistent with acral discoid LE. At 24 months, she had proteinuria and hematuria. Renal biopsy showed class IV S(A) diffuse proliferative lupus nephritis with lupus microangiopathy (<xref rid="fig1" ref-type="fig">Fig 1</xref>). She was treated with cyclophosphamide, a switch from azathioprine to mycophenolate mofetil, and ustekinumab discontinuation.<fig id="fig1"><label>Fig 1</label><caption><p>Presentation with small plaque/papular psoriasis on sun-exposed areas in a patient with prior SLE (<bold>A</bold>). Development of proximal nail fold infarcts (<bold>B</bold>) 10 months after ustekinumab therapy. Periodic acid–Schiff–stained glomerulus shows segmental endocapillary hypercellularity and a small cellular crescent (<bold>C</bold>). (Original magnification: ×200)</p></caption><graphic xlink:href="gr1"></graphic></fig></p></sec><sec id="sec2.2"><title>Case 2</title><p id="p0030">A man in his 40s presented with psoriasis and psoriatic arthritis (PsA). His skin was treated with topical therapy and phototherapy. His antinuclear antibody (ANA) was negative. His PsA was refractory to hydroxychloroquine, nonsteroidal anti-inflammatory agents, sulfasalazine, leflunomide, methotrexate, and cyclosporine. He subsequently did not respond to infliximab, adalimumab, golimumab, and etanercept and remained ANA<sup>−</sup>. Treatment with ustekinumab (45 mg every 12 weeks) was started 15 years after presentation, with significant improvement of his skin (PASI score from 13.6 to 5.2), but limited improvement of PsA. Eleven months after initiation, his ustekinumab dose was increased from 45 to 90 mg every 12 weeks for better joint control. His PASI improved further to 0.3. At 24 months, the patient was hospitalized with worsening renal function and palpable purpura (<xref rid="fig2" ref-type="fig">Fig 2</xref>). A renal biopsy showed full house granular immune-reactant deposition (IgG, IgM, IgA, C1q, and C3) at the glomerular basement membrane consistent with membranoproliferative glomerulonephritis with immune complexes. Skin biopsy confirmed leukocytoclastic vasculitis with a positive lupus band but no vascular immune reactants (<xref rid="fig2" ref-type="fig">Fig 2</xref>). Additional investigations found a positive ANA at 1:80 speckled pattern and low C3 levels. The diagnosis was probable SLE. The patient was treated with cyclophosphamide, but he had persistent renal failure.<fig id="fig2"><label>Fig 2</label><caption><p>Palpable purpura in patient with prior psoriasis and psoriatic arthritis at 24 months of ustekinumab therapy (<bold>A</bold>). Biopsy-confirmed leukocytoclastic vasculitis with perivascular neutrophils, leukocytoclastic debris, and red blood cell extravasation with no vascular immunoglobulin or complement deposition but with full-house granular immune-reactant deposition (IgG, IgM, IgA, C3) at the basement membrane zone (<bold>B</bold>). (IgG direct immunofluorescence; original magnification, ×100.)</p></caption><graphic xlink:href="gr2"></graphic></fig></p></sec><sec id="sec2.3"><title>Case 3</title><p id="p0035">A female in her 20s was assessed for SLE and psoriasis. She had presented in her teens with malar rash, parotitis, interstitial lung disease, arthritis, and retinal vasculitis. SLE was diagnosed, and she was treated with intravenous methylprednisolone. Her course was complicated by macrophage activation syndrome requiring cyclosporine and cyclophosphamide. She was subsequently maintained on mycophenolate mofetil with subsequent minimal disease activity. Psoriasis developed, and she was started on ustekinumab 4 years later. Because her SLE was stable, mycophenolate mofetil was held. Nephrotic syndrome with class V lupus nephritis developed after 3 months of ustekinumab treatment, requiring renewed corticosteroids and mycophenolate mofetil. Her nephritis was ascribed to mycophenolate mofetil discontinuation, and ustekinumab was continued with good control of skin (previously described in Tselios et al<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref>).</p></sec></sec><sec id="sec3"><title>Discussion</title><p id="p0040">The use of ustekinumab in psoriasis is associated with an excellent safety profile. However, isolated reports exist of immune-mediated adverse events in patients treated with this drug: cases of small vessel vasculitis,<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> bullous pemphigoid,<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref> and linear IgA bullous dermatosis<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> have been described. These cases indicate that antibody-antigen complex disease (vasculitis) and loss of B-cell tolerance with autoantibody-mediated disease (immune-bullous disease) may occur in patients undergoing IL-12 and IL-23 inhibition (<xref rid="tbl1" ref-type="table">Table I</xref>).<table-wrap position="float" id="tbl1"><label>Table I</label><caption><p>Autoantibody and antibody-mediated immune phenomena in patients treated with ustekinumab</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Age</th><th>Sex</th><th>Ustekinumab indication</th><th>Prior autoimmune-mediated disease</th><th>New clinical manifestation after ustekinumab</th><th>Ustekinumab duration at time of onset of new disease (mo)</th><th>Study</th></tr></thead><tbody><tr><td>43</td><td>F</td><td>Psoriasis</td><td>Prior SLE</td><td>Lupus nephritis vasculopathy</td><td>20</td><td>Current study</td></tr><tr><td>46</td><td>M</td><td>Psoriasis<break></break>Psoriatic arthritis</td><td>None</td><td>Probable lupus<break></break>Nephritis (membranoproliferative glomerulonephritis with immune complex)<break></break>Vasculitis</td><td>24</td><td>Current study</td></tr><tr><td>25</td><td>F</td><td>Psoriasis</td><td>Prior SLE</td><td>Lupus nephritis</td><td>3 – Ustekinumab continued</td><td>Current study and Tselios et al,<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> 2017</td></tr><tr><td>62<break></break>63<break></break>58</td><td>M<break></break>M<break></break>M</td><td>Psoriasis<break></break>Psoriatic arthritis<break></break>Psoriasis</td><td>None<break></break>Not reported<break></break>Not reported</td><td>Bullous pemphigoid</td><td>10<break></break>18<break></break>2</td><td>Le Guern et al,<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref> 2015<break></break>Nakayama et al,<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> 2015<break></break>Onsun et al,<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref> 2017</td></tr><tr><td>31</td><td>F</td><td>Psoriasis</td><td>Not reported</td><td>Linear IgA bullous dermatosis</td><td>2</td><td>Becker 2016<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref></td></tr></tbody></table></table-wrap></p><p id="p0045">SLE is a complex disease with multiple manifestations. A defect in dead cell clearance and type 1 interferon production are thought to underlie the susceptibility for SLE resulting in dysregulated cell-mediated autoimmunity as noted in cutaneous disease and autoantibody-mediated immunity as noted in renal disease. The cases described here share the onset of autoantibody-mediated nephritis at 3 to 24 months after ustekinumab therapy for psoriasis. Two cases include the development of small vessel vasculitis/vasculopathy. These events occurred with a variable delay after the introduction of ustekinumab, akin to paradoxical psoriasis described with the use of tumor necrosis factor inhibitors. The potential role of ustekinumab is highlighted by the overall lower incidence of lupus nephritis and vasculitis noted in patients with concurrent SLE and psoriasis compared with SLE alone.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Although these rare events do not prove causality, we propose that augmentation of autoantibody production and autoantibody-related disease may be a consequence of simultaneous IL-12 and IL-23 inhibition. Patients with SLE have been noted to have low levels of IL-12 and p34 RNA suggesting that inhibition of this cytokine may promote a shift to Th2 immunity.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> Ongoing therapy with ustekinumab in case 3 did not lead to further autoantibody-mediated immunity, suggesting a stochastic element to this effect. Further, the development of ANAs in patients with psoriasis treated with ustekinumab is likely a rare event.<xref rid="bib14" ref-type="bibr"><sup>14</sup></xref></p><p id="p0050">Clinicians and investigators should be aware of the possibility of enhancement of antibody-mediated autoimmunity in patients with SLE treated with ustekinumab. Because B-cell–activating factor of the tumor necrosis factor family (BAFF) polymorphisms have been associated with B-cell–mediated autoimmunity,<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref> the role of this polymorphism and BAFF levels in exacerbation of disease after ustekinumab therapy deserves further investigation.</p></sec></body><back><ref-list id="cebib0010"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Tselios</surname><given-names>K.</given-names></name><name><surname>Yap</surname><given-names>K.S.</given-names></name><name><surname>Pakchotanon</surname><given-names>R.</given-names></name></person-group><article-title>Psoriasis in systemic lupus erythematosus: a single-center experience</article-title><source>Clin Rheumatol</source><volume>36</volume><issue>4</issue><year>2017</year><fpage>879</fpage><lpage>884</lpage><pub-id pub-id-type="pmid">28168661</pub-id></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="journal" id="sref2"><person-group person-group-type="author"><name><surname>Millns</surname><given-names>J.L.</given-names></name><name><surname>Muller</surname><given-names>S.A.</given-names></name></person-group><article-title>The coexistence of psoriasis and lupus erythematosus. An analysis of 27 cases</article-title><source>Arch Dermatol</source><volume>116</volume><issue>6</issue><year>1980</year><fpage>658</fpage><lpage>663</lpage><pub-id pub-id-type="pmid">7377802</pub-id></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="journal" id="sref3"><person-group person-group-type="author"><name><surname>Zalla</surname><given-names>M.J.</given-names></name><name><surname>Muller</surname><given-names>S.A.</given-names></name></person-group><article-title>The coexistence of psoriasis with lupus erythematosus and other photosensitive disorders</article-title><source>Acta Derm-Venereol Suppl</source><volume>195</volume><year>1996</year><fpage>1</fpage><lpage>15</lpage></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="journal" id="sref4"><person-group person-group-type="author"><name><surname>De Souza</surname><given-names>A.</given-names></name><name><surname>Ali-Shaw</surname><given-names>T.</given-names></name><name><surname>Strober</surname><given-names>B.E.</given-names></name><name><surname>Franks</surname><given-names>A.G.</given-names><suffix>Jr.</suffix></name></person-group><article-title>Successful treatment of subacute lupus erythematosus with ustekinumab</article-title><source>Arch Dermatol</source><volume>147</volume><issue>8</issue><year>2011</year><fpage>896</fpage><lpage>898</lpage><pub-id pub-id-type="pmid">21844448</pub-id></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sref5"><person-group person-group-type="author"><name><surname>Winchester</surname><given-names>D.</given-names></name><name><surname>Duffin</surname><given-names>K.C.</given-names></name><name><surname>Hansen</surname><given-names>C.</given-names></name></person-group><article-title>Response to ustekinumab in a patient with both severe psoriasis and hypertrophic cutaneous lupus</article-title><source>Lupus</source><volume>21</volume><issue>9</issue><year>2012</year><fpage>1007</fpage><lpage>1010</lpage><pub-id pub-id-type="pmid">22438028</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sref6"><person-group person-group-type="author"><name><surname>Varada</surname><given-names>S.</given-names></name><name><surname>Gottlieb</surname><given-names>A.B.</given-names></name><name><surname>Merola</surname><given-names>J.F.</given-names></name><name><surname>Saraiya</surname><given-names>A.R.</given-names></name><name><surname>Tintle</surname><given-names>S.J.</given-names></name></person-group><article-title>Treatment of coexistent psoriasis and lupus erythematosus</article-title><source>J Am Acad Dermatol</source><volume>72</volume><issue>2</issue><year>2015</year><fpage>253</fpage><lpage>260</lpage><pub-id pub-id-type="pmid">25486913</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sref7"><person-group person-group-type="author"><name><surname>van Vollenhoven</surname><given-names>R.F.</given-names></name><name><surname>Hahn</surname><given-names>B.H.</given-names></name><name><surname>Tsokos</surname><given-names>G.C.</given-names></name></person-group><article-title>Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study</article-title><source>Lancet</source><volume>392</volume><issue>10155</issue><year>2018</year><fpage>1330</fpage><lpage>1339</lpage><pub-id pub-id-type="pmid">30249507</pub-id></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sref8"><person-group person-group-type="author"><name><surname>MacArthur</surname><given-names>K.M.</given-names></name><name><surname>Merkel</surname><given-names>P.A.</given-names></name><name><surname>Van Voorhees</surname><given-names>A.S.</given-names></name><name><surname>Nguyen</surname><given-names>J.</given-names></name><name><surname>Rosenbach</surname><given-names>M.</given-names></name></person-group><article-title>Severe small-vessel vasculitis temporally associated with administration of ustekinumab</article-title><source>J Drugs Dermatol</source><volume>15</volume><issue>3</issue><year>2016</year><fpage>359</fpage><lpage>362</lpage><pub-id pub-id-type="pmid">26954323</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sref9"><person-group person-group-type="author"><name><surname>Le Guern</surname><given-names>A.</given-names></name><name><surname>Alkeraye</surname><given-names>S.</given-names></name><name><surname>Vermersch-Langlin</surname><given-names>A.</given-names></name><name><surname>Coupe</surname><given-names>P.</given-names></name><name><surname>Vonarx</surname><given-names>M.</given-names></name></person-group><article-title>Bullous pemphigoid during ustekinumab therapy</article-title><source>JAAD Case Rep</source><volume>1</volume><issue>6</issue><year>2015</year><fpage>359</fpage><lpage>360</lpage><pub-id pub-id-type="pmid">27051780</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sref10"><person-group person-group-type="author"><name><surname>Nakayama</surname><given-names>C.</given-names></name><name><surname>Fujita</surname><given-names>Y.</given-names></name><name><surname>Watanabe</surname><given-names>M.</given-names></name><name><surname>Shimizu</surname><given-names>H.</given-names></name></person-group><article-title>Development of bullous pemphigoid during treatment of psoriatic onycho-pachydermo periostitis with ustekinumab</article-title><source>J Dermatol</source><volume>42</volume><issue>10</issue><year>2015</year><fpage>996</fpage><lpage>998</lpage><pub-id pub-id-type="pmid">26010891</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sref11"><person-group person-group-type="author"><name><surname>Onsun</surname><given-names>N.</given-names></name><name><surname>Sallahoglu</surname><given-names>K.</given-names></name><name><surname>Dizman</surname><given-names>D.</given-names></name><name><surname>Su</surname><given-names>O.</given-names></name><name><surname>Tosuner</surname><given-names>Z.</given-names></name></person-group><article-title>Bullous pemphigoid during ustekinumab therapy in a psoriatic patient</article-title><source>Eur J Dermatol</source><volume>27</volume><issue>1</issue><year>2017</year><fpage>81</fpage><lpage>82</lpage><pub-id pub-id-type="pmid">27777186</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sref12"><person-group person-group-type="author"><name><surname>Becker</surname><given-names>J.G.</given-names></name><name><surname>Mundi</surname><given-names>J.P.</given-names></name><name><surname>Newlove</surname><given-names>T.</given-names></name><name><surname>Mones</surname><given-names>J.</given-names></name><name><surname>Shupack</surname><given-names>J.</given-names></name></person-group><article-title>Development of linear IgA bullous dermatosis in a patient with psoriasis taking ustekinumab</article-title><source>J Am Acad Dermatol</source><volume>67</volume><issue>4</issue><year>2012</year><fpage>e150</fpage><lpage>e151</lpage><pub-id pub-id-type="pmid">22980274</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sref13"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>T.F.</given-names></name><name><surname>Jones</surname><given-names>B.M.</given-names></name><name><surname>Wong</surname><given-names>R.W.</given-names></name><name><surname>Srivastava</surname><given-names>G.</given-names></name></person-group><article-title>Impaired production of IL-12 in systemic lupus erythematosus. III: deficient IL-12 p40 gene expression and cross-regulation of IL-12, IL-10 and IFN-gamma gene expression</article-title><source>Cytokine</source><volume>11</volume><issue>10</issue><year>1999</year><fpage>805</fpage><lpage>811</lpage><pub-id pub-id-type="pmid">10525320</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="journal" id="sref14"><person-group person-group-type="author"><name><surname>Rodriguez-Jimenez</surname><given-names>P.</given-names></name><name><surname>Chicharro</surname><given-names>P.</given-names></name><name><surname>Godoy</surname><given-names>A.</given-names></name><name><surname>Llamas-Velasco</surname><given-names>M.</given-names></name><name><surname>Garcia</surname><given-names>M.</given-names></name><name><surname>Dauden</surname><given-names>E.</given-names></name></person-group><article-title>No evidence for induction of autoantibodies or autoimmunity during treatment of psoriasis with ustekinumab</article-title><source>Br J Dermatol</source><volume>177</volume><issue>3</issue><year>2017</year><fpage>862</fpage><lpage>863</lpage><pub-id pub-id-type="pmid">28508387</pub-id></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sref15"><person-group person-group-type="author"><name><surname>Steri</surname><given-names>M.</given-names></name><name><surname>Orru</surname><given-names>V.</given-names></name><name><surname>Idda</surname><given-names>M.L.</given-names></name></person-group><article-title>Overexpression of the Cytokine BAFF and autoimmunity risk</article-title><source>N Engl J Med</source><volume>376</volume><issue>17</issue><year>2017</year><fpage>1615</fpage><lpage>1626</lpage><pub-id pub-id-type="pmid">28445677</pub-id></element-citation></ref></ref-list><ack id="ack0010"><p>Dr Dutz is a Senior Scientist at the BC Children's Hospital Research Institute. Dr Al Khalili received an immune-dermatology fellowship award from the Sultanate of Oman. We would like to thank Dr Martin Trotter for cutaneous histopathology and immune-histology expertise, Drs Mei Lin Bissonette and Alexander Magil for renal pathology and immune-histology, and Dr Jose Guerrero for helpful comments.</p></ack><fn-group><fn id="d31e199"><p id="ntpara0010">Funding sources: None.</p></fn><fn id="d31e202"><p id="ntpara0015">Conflicts of interest: Dr Dutz has received consulting fees and speaker's fees from Abbvie, Amgen, Celgene, Janssen, Leo Pharma, Novartis and Pfizer. The rest of the authors have no conflicts to disclose.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0003099 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0003099 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.33. |  |