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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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Vol. 110. Núm. 9.
Páginas 776-778 (noviembre 2019)
Vol. 110. Núm. 9.
Páginas 776-778 (noviembre 2019)
Case and Research Letters
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Pyoderma Gangrenosum With Ulcerative Colitis Successfully Treated With Ustekinumab
Pioderma gangrenoso asociado a colitis ulcerosa con buena respuesta a ustekinumab
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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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Table 1. Summary of Cases of Pyoderma Gangrenosum Treated With Ustekinumab Reported in the Literature.
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To the Editor:

Pyoderma gangrenosum is a rare neutrophilic skin disease that may be idiopathic or associated with systemic disease such as inflammatory bowel disease, arthritis, paraproteinemia, or blood cancers. 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, in most cases, systemic immunosuppressant treatment is required. Corticosteroids and cyclosporin are used as the first line in systemic treatments. Other reported alternatives, although not approved for this indication, include mycophenolate mofetil, anti-TNF, intravenous immunoglobulins, interleukin (IL) 1 antagonists, and ustekinumab (anti-IL-12/23).1

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. The patient had been treated with multiple therapies that, in chronological order, included 6-mercaptopurine, cyclosporin at 3-5mg/kg/d for 5 months, intravenous infliximab at 5mg/kg every 4 weeks, subcutaneous adalimumab at 40mg/wk, plasmapheresis every 15 days, tacrolimus oral at 8mg/d, intravenous vedolizumab at 300mg every 4 weeks, and subtotal colectomy. Cyclosporin, infliximab, adalimumab, 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, and topical tacrolimus and clobetasol propionate. All previous treatments were associated with prednisone at doses of up to 50mg/d. At one point in the course of the disease, the patient presented left pretibial pyoderma gangrenosum measuring 11×7cm. The lesion, which had appeared 5 months earlier, was difficult to manage, corticosteroid-dependent (it worsened when prednisone was reduced to below 20mg/d), and had a considerable impact on quality of life (Fig. 1). At the time, the patient was undergoing treatment with intravenous vedolizumab at a dosage of 300mg every 4 weeks, prednisone at 50mg/d, and topical corticosteroids. In light of the refractory nature of the disease and as multiple lines of treatment had been exhausted, it was decided to instate treatment with subcutaneous ustekinumab 90mg (week 0, 4, 10, and every 8 weeks thereafter) associated with cyclosporin at a dose of 3mg/kg/d, with an excellent response of the pyoderma gangrenosum, which resolved completely in 12 weeks, making it possible to reduce the dosage of prednisone to 5mg/d (Fig. 2). After 10 months of follow-up, the patient has maintained treatment with ustekinumab every 8 weeks with very good results; this has made it possible to withdraw the cyclosporin and reduce the prednisone to 2.5mg every 2 days.

Figure 1.

Skin lesion compatible with pyoderma gangrenosum on the lower part of the left leg. Image prior to combined treatment with ustekinumab and cyclosporin.

(0.09MB).
Figure 2.

Residual lesion on the left leg after treatment with ustekinumab and cyclosporin for 12 weeks.

(0.05MB).

In 2011, Guenova et al reported the first case of pyoderma gangrenosum successfully treated with ustekinumab.2 Those authors suggested that IL-23 is implicated in the pathogenesis of immunologic diseases such as psoriasis and inflammatory bowel disease; they therefore studied the expression of this interleukin in the patient's lesion biopsy and observed overexpression of IL-23 compared to biopsies of healthy skin. Ustekinumab was therefore proposed as a targeted therapy for treatment of the pyoderma gangrenosum.2 Since then, 5 more cases have been reported in the literature with good response to ustekinumab at doses ranging from 45-90mg every 8 weeks to 135mg every 6 weeks (Table 1).2–7

Table 1.

Summary of Cases of Pyoderma Gangrenosum Treated With Ustekinumab Reported in the Literature.

Author  Sex/Age, y  Associated Disease  Previous Treatment  Ustekinumab Dosage  Response 
Guenova et al.2 (2011)  Female/37  None  Prednisolone and tacrolimus topical  45mg/8 weeksAssociated with tacrolimus topical  Complete response reached after 14 weeks 
Fahmy et al.3 (2012)  Female/34  Ulcerative colitis  Corticosteroids, azathioprine, infliximab, colectomy, adalimumab, and tacrolimus oral  90mg/8 weeks  Complete response reached after 10 weeks 
Goldminz et al.4 (2012)  Male/37  None  Topical, intralesional, and systemic corticosteroids, cyclosporin, azathioprine, methotrexate, adalimumab, infliximab, and golimumab  90mg/8 weeksAssociated with dapsone 100mg/d and prednisone  Complete response reached after 22 weeks 
Cosgarea et al.5 (2016)  Female/71  Renal cell carcinoma  Prednisone and cyclosporin  Not reported  Complete response reached 12 weeks after reinstatement of ustekinumab following surgery for renal cell carcinoma (no response prior to surgery) 
Greb et al.6 (2016)  Male/50  None  Prednisone, cyclosporin, adalimumab, infliximab, and golimumab  90mg/8 weeks to 135mg/6 weeksAssociated with dapsone 100mg/d and prednisone  Response reached after 16 weeks following higher dosage of ustekinumab 
Benzaquen et al.7 (2017)  Female/56  Psoriasis treated with adalimumab (induced by anti-TNF)  None  45mg. Interval not specified  Complete response after 3 doses 

In conclusion, we present a new case of pyoderma gangrenosum associated with ulcerative colitis, with good response to ustekinumab together with cyclosporin and oral corticosteroids following a lack of response to the 2 previous treatments, tacrolimus oral and anti-TNF (infliximab and adalimumab), administered together. We propose this alternative in difficult-to-manage cases of pyoderma gangrenosum that are refractory to other treatments. Further studies are required to determine the involvement of IL-23 in the pathogenesis of this disease.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References
[1]
S.R. Quist, L. Kraas.
Treatment options for pyoderma gangrenosum.
J Dtsch Dermatol Ges, 15 (2017), pp. 34-40
[2]
E. Guenova, A. Teske, B. Fehrenbacher, S. Hoerber, A. Adamczyk, M. Schaller, et al.
Interleukin 23 expression in pyoderma gangrenosum and targeted therapy with ustekinumab.
Arch Dermatol, 147 (2011), pp. 1203-1205
[3]
M. Fahmy, S. Ramamoorthy, T. Hata, W.J. Sandborn.
Ustekinumab for peristomal pyoderma gangrenosum.
Am J Gastroenterol, 107 (2012), pp. 794-795
[4]
A.M. Goldminz, N.C. Botto, A.B. Gottlieb.
Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab.
J Am Acad Dermatol, 67 (2012), pp. e237-e238
[5]
I. Cosgarea, Z. Lovric, A. Körber, J. Dissemond.
Successful treatment of refractory pyoderma gangrenosum with ustekinumab only after excision of renal cell carcinoma.
Int Wound J, 13 (2016), pp. 1041-1042
[6]
J.E. Greb, A.B. Gottlieb, A.M. Goldminz.
High-dose ustekinumab for the treatment of severe, recalcitrant pyoderma gangrenosum.
Dermatol Ther, 29 (2016), pp. 482-483
[7]
M. Benzaquen, J. Monnier, Y. Beaussault, F. Rouby, P. Berbis.
Pyoderma gangrenosum arising during treatment of psoriasis with adalimumab: Effectiveness of ustekinumab.
Australas J Dermatol, 58 (2017), pp. e270-e271

Please cite this article as: Piqueras-García J, Sahuquillo-Torralba AJ, Torres-Navarro I, Botella-Estrada R. Pioderma gangrenoso asociado a colitis ulcerosa con buena respuesta a ustekinumab Eczema y urticaria en Portugal. 2019;110:776–778.

Copyright © 2019. Elsevier España, S.L.U. and AEDV
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