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The patient had been treated with multiple therapies that&#44; in chronological order&#44; included 6-mercaptopurine&#44; cyclosporin at 3-5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 5 months&#44; intravenous infliximab at 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 4 weeks&#44; subcutaneous adalimumab at 40<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&#44; plasmapheresis every 15 days&#44; tacrolimus oral at 8<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; intravenous vedolizumab at 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#44; and subtotal colectomy&#46; Cyclosporin&#44; infliximab&#44; adalimumab&#44; and tacrolimus oral had been administered with the above treatments for the indication of pyoderma gangrenosum and topical treatment was associated with intralesional triamcinolone acetonide&#44; and topical tacrolimus and clobetasol propionate&#46; All previous treatments were associated with prednisone at doses of up to 50<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; At one point in the course of the disease&#44; the patient presented left pretibial pyoderma gangrenosum measuring 11<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>cm&#46; The lesion&#44; which had appeared 5 months earlier&#44; was difficult to manage&#44; corticosteroid-dependent &#40;it worsened when prednisone was reduced to below 20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#44; and had a considerable impact on quality of life &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; At the time&#44; the patient was undergoing treatment with intravenous vedolizumab at a dosage of 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#44; prednisone at 50<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; and topical corticosteroids&#46; In light of the refractory nature of the disease and as multiple lines of treatment had been exhausted&#44; it was decided to instate treatment with subcutaneous ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;week 0&#44; 4&#44; 10&#44; and every 8 weeks thereafter&#41; associated with cyclosporin at a dose of 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#44; with an excellent response of the pyoderma gangrenosum&#44; which resolved completely in 12 weeks&#44; making it possible to reduce the dosage of prednisone to 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; After 10 months of follow-up&#44; the patient has maintained treatment with ustekinumab every 8 weeks with very good results&#59; this has made it possible to withdraw the cyclosporin and reduce the prednisone to 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg every 2 days&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In 2011&#44; Guenova et al reported the first case of pyoderma gangrenosum successfully treated with ustekinumab&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Those authors suggested that IL-23 is implicated in the pathogenesis of immunologic diseases such as psoriasis and inflammatory bowel disease&#59; they therefore studied the expression of this interleukin in the patient&#39;s lesion biopsy and observed overexpression of IL-23 compared to biopsies of healthy skin&#46; Ustekinumab was therefore proposed as a targeted therapy for treatment of the pyoderma gangrenosum&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Since then&#44; 5 more cases have been reported in the literature with good response to ustekinumab at doses ranging from 45-90<span class="elsevierStyleHsp" style=""></span>mg every 8 weeks to 135<span class="elsevierStyleHsp" style=""></span>mg every 6 weeks &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#8211;7</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a new case of pyoderma gangrenosum associated with ulcerative colitis&#44; with good response to ustekinumab together with cyclosporin and oral corticosteroids following a lack of response to the 2 previous treatments&#44; tacrolimus oral and anti-TNF &#40;infliximab and adalimumab&#41;&#44; administered together&#46; We propose this alternative in difficult-to-manage cases of pyoderma gangrenosum that are refractory to other treatments&#46; Further studies are required to determine the involvement of IL-23 in the pathogenesis of this disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Residual lesion on the left leg after treatment with ustekinumab and cyclosporin for 12 weeks&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sex&#47;Age&#44; y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Associated Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Previous Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ustekinumab Dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guenova et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisolone and tacrolimus topical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeksAssociated with tacrolimus topical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 14 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fahmy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulcerative colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corticosteroids&#44; azathioprine&#44; infliximab&#44; colectomy&#44; adalimumab&#44; and tacrolimus oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 10 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Goldminz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&#47;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Topical&#44; intralesional&#44; and systemic corticosteroids&#44; cyclosporin&#44; azathioprine&#44; methotrexate&#44; adalimumab&#44; infliximab&#44; and golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeksAssociated with dapsone 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d and prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 22 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cosgarea et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal cell carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone and cyclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not reported&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached 12 weeks after reinstatement of ustekinumab following surgery for renal cell carcinoma &#40;no response prior to surgery&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Greb et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&#47;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&#44; cyclosporin&#44; adalimumab&#44; infliximab&#44; and golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeks to 135<span class="elsevierStyleHsp" style=""></span>mg&#47;6 weeksAssociated with dapsone 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d and prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Response reached after 16 weeks following higher dosage of ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benzaquen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> &#40;2017&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis treated with adalimumab &#40;induced by anti-TNF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>mg&#46; Interval not specified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response after 3 doses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Summary of Cases of Pyoderma Gangrenosum Treated With Ustekinumab Reported in the Literature&#46;</p>"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment options for pyoderma gangrenosum"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;R&#46; Quist"
                            1 => "L&#46; Kraas"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ddg.13173"
                      "Revista" => array:7 [
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                        "fecha" => "2017"
                        "volumen" => "15"
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                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28140549"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Guenova"
                            1 => "A&#46; Teske"
                            2 => "B&#46; Fehrenbacher"
                            3 => "S&#46; Hoerber"
                            4 => "A&#46; Adamczyk"
                            5 => "M&#46; Schaller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archdermatol.2011.168"
                      "Revista" => array:6 [
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                            "web" => "Medline"
                          ]
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                      ]
                    ]
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            2 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ustekinumab for peristomal pyoderma gangrenosum"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "M&#46; Fahmy"
                            1 => "S&#46; Ramamoorthy"
                            2 => "T&#46; Hata"
                            3 => "W&#46;J&#46; Sandborn"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
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                      "doi" => "10.1038/ajg.2012.42"
                      "Revista" => array:6 [
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                  "contribucion" => array:1 [
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                          "etal" => false
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                            0 => "A&#46;M&#46; Goldminz"
                            1 => "N&#46;C&#46; Botto"
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                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2012.04.045"
                      "Revista" => array:6 [
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                        "volumen" => "67"
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                ]
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              "identificador" => "bib0060"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Successful treatment of refractory pyoderma gangrenosum with ustekinumab only after excision of renal cell carcinoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "I&#46; Cosgarea"
                            1 => "Z&#46; Lovric"
                            2 => "A&#46; K&#246;rber"
                            3 => "J&#46; Dissemond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/iwj.12377"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int Wound J"
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Case and Research Letters
Pyoderma Gangrenosum With Ulcerative Colitis Successfully Treated With Ustekinumab
Pioderma gangrenoso asociado a colitis ulcerosa con buena respuesta a ustekinumab
J. Piqueras-García
Autor para correspondencia
jennipg_19@hotmail.com

Corresponding author.
, A.J. Sahuquillo-Torralba, I. Torres-Navarro, R. Botella-Estrada
Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pyoderma gangrenosum is a rare neutrophilic skin disease that may be idiopathic or associated with systemic disease such as inflammatory bowel disease&#44; arthritis&#44; paraproteinemia&#44; or blood cancers&#46; While it is true that topical or intralesional therapies can be used in patients with isolated lesions that have little impact on quality of life&#44; in most cases&#44; systemic immunosuppressant treatment is required&#46; Corticosteroids and cyclosporin are used as the first line in systemic treatments&#46; Other reported alternatives&#44; although not approved for this indication&#44; include mycophenolate mofetil&#44; anti-TNF&#44; intravenous immunoglobulins&#44; interleukin &#40;IL&#41; 1 antagonists&#44; and ustekinumab &#40;anti-IL-12&#47;23&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 33-year-old woman diagnosed with ulcerative colitis since the age of 17 years had presented multiple pyoderma gangrenosum lesions on the lower limbs throughout the course of the disease&#46; The patient had been treated with multiple therapies that&#44; in chronological order&#44; included 6-mercaptopurine&#44; cyclosporin at 3-5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d for 5 months&#44; intravenous infliximab at 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 4 weeks&#44; subcutaneous adalimumab at 40<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&#44; plasmapheresis every 15 days&#44; tacrolimus oral at 8<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; intravenous vedolizumab at 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#44; and subtotal colectomy&#46; Cyclosporin&#44; infliximab&#44; adalimumab&#44; and tacrolimus oral had been administered with the above treatments for the indication of pyoderma gangrenosum and topical treatment was associated with intralesional triamcinolone acetonide&#44; and topical tacrolimus and clobetasol propionate&#46; All previous treatments were associated with prednisone at doses of up to 50<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#46; At one point in the course of the disease&#44; the patient presented left pretibial pyoderma gangrenosum measuring 11<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>7<span class="elsevierStyleHsp" style=""></span>cm&#46; The lesion&#44; which had appeared 5 months earlier&#44; was difficult to manage&#44; corticosteroid-dependent &#40;it worsened when prednisone was reduced to below 20<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#41;&#44; and had a considerable impact on quality of life &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; At the time&#44; the patient was undergoing treatment with intravenous vedolizumab at a dosage of 300<span class="elsevierStyleHsp" style=""></span>mg every 4 weeks&#44; prednisone at 50<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#44; and topical corticosteroids&#46; In light of the refractory nature of the disease and as multiple lines of treatment had been exhausted&#44; it was decided to instate treatment with subcutaneous ustekinumab 90<span class="elsevierStyleHsp" style=""></span>mg &#40;week 0&#44; 4&#44; 10&#44; and every 8 weeks thereafter&#41; associated with cyclosporin at a dose of 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#44; with an excellent response of the pyoderma gangrenosum&#44; which resolved completely in 12 weeks&#44; making it possible to reduce the dosage of prednisone to 5<span class="elsevierStyleHsp" style=""></span>mg&#47;d &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; After 10 months of follow-up&#44; the patient has maintained treatment with ustekinumab every 8 weeks with very good results&#59; this has made it possible to withdraw the cyclosporin and reduce the prednisone to 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg every 2 days&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In 2011&#44; Guenova et al reported the first case of pyoderma gangrenosum successfully treated with ustekinumab&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Those authors suggested that IL-23 is implicated in the pathogenesis of immunologic diseases such as psoriasis and inflammatory bowel disease&#59; they therefore studied the expression of this interleukin in the patient&#39;s lesion biopsy and observed overexpression of IL-23 compared to biopsies of healthy skin&#46; Ustekinumab was therefore proposed as a targeted therapy for treatment of the pyoderma gangrenosum&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Since then&#44; 5 more cases have been reported in the literature with good response to ustekinumab at doses ranging from 45-90<span class="elsevierStyleHsp" style=""></span>mg every 8 weeks to 135<span class="elsevierStyleHsp" style=""></span>mg every 6 weeks &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2&#8211;7</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a new case of pyoderma gangrenosum associated with ulcerative colitis&#44; with good response to ustekinumab together with cyclosporin and oral corticosteroids following a lack of response to the 2 previous treatments&#44; tacrolimus oral and anti-TNF &#40;infliximab and adalimumab&#41;&#44; administered together&#46; We propose this alternative in difficult-to-manage cases of pyoderma gangrenosum that are refractory to other treatments&#46; Further studies are required to determine the involvement of IL-23 in the pathogenesis of this disease&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:2 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Conflicts of Interest"
        ]
        1 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Piqueras-Garc&#237;a J&#44; Sahuquillo-Torralba AJ&#44; Torres-Navarro I&#44; Botella-Estrada R&#46; Pioderma gangrenoso asociado a colitis ulcerosa con buena respuesta a ustekinumab Eczema y urticaria en Portugal&#46; 2019&#59;110&#58;776&#8211;778&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 589
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Skin lesion compatible with pyoderma gangrenosum on the lower part of the left leg&#46; Image prior to combined treatment with ustekinumab and cyclosporin&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Residual lesion on the left leg after treatment with ustekinumab and cyclosporin for 12 weeks&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sex&#47;Age&#44; y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Associated Disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Previous Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ustekinumab Dosage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guenova et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> &#40;2011&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisolone and tacrolimus topical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeksAssociated with tacrolimus topical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 14 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fahmy et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ulcerative colitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corticosteroids&#44; azathioprine&#44; infliximab&#44; colectomy&#44; adalimumab&#44; and tacrolimus oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 10 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Goldminz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> &#40;2012&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&#47;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Topical&#44; intralesional&#44; and systemic corticosteroids&#44; cyclosporin&#44; azathioprine&#44; methotrexate&#44; adalimumab&#44; infliximab&#44; and golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeksAssociated with dapsone 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d and prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached after 22 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cosgarea et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal cell carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone and cyclosporin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not reported&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response reached 12 weeks after reinstatement of ustekinumab following surgery for renal cell carcinoma &#40;no response prior to surgery&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Greb et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> &#40;2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male&#47;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisone&#44; cyclosporin&#44; adalimumab&#44; infliximab&#44; and golimumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90<span class="elsevierStyleHsp" style=""></span>mg&#47;8 weeks to 135<span class="elsevierStyleHsp" style=""></span>mg&#47;6 weeksAssociated with dapsone 100<span class="elsevierStyleHsp" style=""></span>mg&#47;d and prednisone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Response reached after 16 weeks following higher dosage of ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benzaquen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> &#40;2017&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female&#47;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis treated with adalimumab &#40;induced by anti-TNF&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45<span class="elsevierStyleHsp" style=""></span>mg&#46; Interval not specified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Complete response after 3 doses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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