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the patient presented a further outbreak at the same sites as the previous outbreak&#44; with purpuric plaques that spread centrifugally&#44; pain&#44; bilateral ankle edema&#44; and fever&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A further biopsy revealed a neutrophilic infiltrate in the small and medium-sized vessels&#44; with fibrinoid necrosis&#44; and a moderate eosinophilic infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A and<span class="elsevierStyleHsp" style=""></span>B&#41;&#46; Based on these findings&#44; we made a diagnosis of PAN&#46; Given the absence of organ involvement&#44; despite the marked elevation of the AFRs and alteration of the patient&#39;s general state of health&#44; we considered this to be cutaneous PAN with an associated systemic inflammatory response&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">After increasing the dose of prednisone to 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d and controlling the acute outbreak&#44; treatment was started with cyclophosphamide and immunoglobulins&#46; However&#44; this did not enable us to reduce the dose of corticosteroids without renewed deterioration&#46; Treatment was therefore commenced with infliximab at a dose of 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; which led to a very good response after the first infusion&#44; with complete normalization of laboratory parameters&#46; The dose of corticosteroids was progressively reduced until their withdrawal&#44; with no further outbreaks of lesions in a year of follow-up&#44; except for a residual livedo &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a><span class="elsevierStyleHsp" style=""></span>C&#41;&#59; during this period the patient continued treatment with infliximab every 8 weeks&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The typical clinical manifestations of cutaneous PAN are characterized by outbreaks of painful nodular lesions that leave a residual livedo&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In the first patient series&#44; dating from 1974&#44; the presence of a starburst pattern was described as a characteristic manifestation of this livedo&#44; and was very similar to that observed in our patient&#44; though we have found no similar descriptions in the recent literature&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Typically&#44; histology reveals a focal panniculitis around affected arteries&#46; However&#44; if the inflammatory infiltrate is very intense&#44; the panniculitis can be so pronounced that it masks the vasculitis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Three subgroups of cutaneous PAN have been described based on the presentation&#44; laboratory tests&#44; and clinical course&#58; class <span class="elsevierStyleSmallCaps">i</span>&#44; in which the cutaneous manifestations are associated with slightly elevated AFRs&#59; class <span class="elsevierStyleSmallCaps">ii</span>&#44; in which constitutional symptoms are also present&#44; with fever and marked elevation of the AFRs&#59; and class <span class="elsevierStyleSmallCaps">iii</span>&#44; in which the cutaneous form progresses to systemic forms of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> We classified our patient in the second subgroup&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In cutaneous PAN&#44; patients with marked elevation of AFRs are more likely to present inflammatory plaques and edema of the lower limbs&#46; Considering this association as a more severe form of the disease&#44; it has been proposed that the initial management approach should be more aggressive to avoid progression to systemic forms&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Although the use of TNF inhibitors is not uncommon in the systemic forms of PAN&#44; we have found very few reports in the literature in which this treatment has been required to control cutaneous forms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; we have presented a case of cutaneous PAN associated with a systemic inflammatory response and refractory to conventional treatments&#46; It is essential to suspect this disease in patients with nodules beneath plaques showing centrifugal spread&#44; even if histology does not initially support the diagnosis&#44; particularly if there is an associated intense inflammatory reaction that could hide the vasculitis&#46; Patients with cutaneous PAN with very high AFRs will often require management similar to the systemic forms&#44; and TNF inhibitors are an option&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Tous-Romero F&#44; Rodr&#237;guez-Almaraz E&#44; Rodr&#237;guez-Peralto JL&#44; Postigo-Llorente C&#46; Panarteritis nudosa con patr&#243;n de respuesta inflamatoria sist&#233;mica&#58; respuesta a anti-TNF&#46; Actas Dermosifiliogr&#46; 2017&#59;108&#58;787&#8211;790&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44; Nodules beneath erythematous plaques with peripheral desquamation&#46; B&#44; In greater detail&#44; showing the residual hyperpigmentation&#46; C&#44; Edema on the dorsum of the left foot&#46; D&#44; Skin biopsy showing a normal epidermis and dermis&#44; with lesions in the subcutaneous cellular tissue&#46; Inflammatory infiltrate in the septa&#46; Hematoxylin and eosin&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;4&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A&#44; Normal epidermis with lesions in the dermis and subcutaneous cellular tissue&#46; Hematoxylin and eosin&#44; original magnification &#215;4&#46; B&#44; Fibrinoid necrosis and a neutrophilic infiltrate in the medium-sized vessels&#44; with an associated eosinophilic infiltrate&#46; Hematoxylin and eosin&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;20&#46;<span class="elsevierStyleHsp" style=""></span>C&#44; Residual livedo on the legs after starting treatment with infliximab&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AZA&#44; azathioprine&#59; CsA&#44; ciclosporin&#59; CY&#44; cyclophosphamide&#59; DFPP&#44; double filtration plasmapheresis&#59; ETN&#44; etanercept&#59; IFX&#44; infliximab&#59; IVIG&#44; intravenous immunoglobulin&#59; MTX&#44; methotrexate&#59; NA&#44; not available&#59; OC&#44; oral corticosteroid therapy&#59; PE&#44; plasma exchange&#59; RTX&#44; rituximab&#59; SSZ&#44; sulfasalazine&#59; TAC&#44; tacrolimus&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Authors&#44; Year&#44; and Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&#44; y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Previous Treatments&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Duration of Previous Treatments&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TNF Inhibitor&#44; Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Concomitant Immunosuppressant Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up&#44; mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome&#47;Adverse Events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Garc&#237;a-Porrua and Gonzalez-Gay&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Indomethacin&#44; SSZ&#44; MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MTX 15<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vega Guti&#233;rrez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bansal and Houghton&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; CY&#44; MTX&#44; IVIG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg first dose&#44; followed by 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 4 wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No response &#40;corticosteroid dependence&#41;&#46; Response to RTX and CY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Zoshima et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&#44; CsA&#44; TAC&#44; CY&#44; AZA&#44; colchicine&#44; PE&#44; DFPP<br>Lamivudine&#44; adefovir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">156&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ETN&#44; 25<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Campanilho-Marques et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&#44; CY&#44; RTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Valor et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; CY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ETN&#44; 25<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&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">Treatment With TNF Inhibitors in Cutaneous Polyarteritis Nodosa&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:10 [
            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous polyarteritis nodosa&#58; A comprehensive review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;J&#46; Morgan"
                            1 => "R&#46;A&#46; Schwartz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-4632.2010.04522.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Dermatol&#46;"
                        "fecha" => "2010"
                        "volumen" => "49"
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                        "paginaFinal" => "756"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20618492"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cutaneous periarteritis nodosa"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;L&#46; Diaz-Perez"
                            1 => "R&#46;K&#46; Winkelmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
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Case and Research Letter
Polyarteritis Nodosa with a Systemic Inflammatory Response Pattern: Effectiveness of anti-TNF
Panarteritis nudosa con patrón de respuesta inflamatoria sistémica: respuesta a anti-TNF
F. Tous-Romeroa,
Autor para correspondencia
fatimatousro@gmail.com

Corresponding author.
, E. Rodríguez-Almarazb, J.L. Rodríguez-Peraltoc, C. Postigo-Llorentea
a Servicio de Dermatología, Hospital Universitario 12 de Octubre, Madrid, Spain
b Servicio de Reumatología, Hospital Universitario 12 de Octubre, Madrid, Spain
c Servicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Polyarteritis nodosa &#40;PAN&#41; is a vasculitis that affects small and medium-sized vessel&#46; It is traditionally divided into 2 forms&#46; The cutaneous form is the variant in which the clinical manifestations are limited to the skin&#44; though muscle pain and generalized joint pain may also be reported&#44; and neuritis in areas close to the affected skin&#46; Fever is detected in up to a third of cases&#46; The systemic form affects internal organs&#44; most commonly the kidney&#44; liver&#44; and central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 50-year-old man was seen in our department for a 5-year history of outbreaks of nodular lesions&#44; initially only affecting the legs&#44; associated with widespread joint pain&#46; In the last year&#44; lesions had also appeared on his arms&#44; and he had developed episodes of fever&#44; weight loss&#44; asthenia&#44; and anorexia&#46; He had been on follow-up at another hospital&#44; where several biopsies had been performed with nonspecific results &#40;a dermal neutrophilic infiltrate&#44; stasis dermatitis&#44; and&#44; in the most recent biopsy&#44; a predominantly lobular panniculitis&#41;&#46; He had received no definitive diagnosis&#46; Despite treatment with various drugs&#44; control of his disease had not been achieved&#59; throughout this whole period he had been administered oral corticosteroids&#44; with intermittent courses of colchicine&#44; azathioprine&#44; methotrexate&#44; and ciclosporin&#46; Important blood test results included elevation of the acute phase reactants &#40;AFRs&#41;&#44; with elevation of C-reactive protein and erythrocyte sedimentation rate &#40;which had risen to 120<span class="elsevierStyleHsp" style=""></span>mm&#47;h in recent months&#41;&#46; Other additional tests&#44; including autoimmunity studies &#40;antinuclear antibodies&#44; extractable nuclear antigen&#44; and antineutrophil cytoplasmic antibodies&#41; and serology &#40;HIV and hepatotropic viruses&#41;&#44; were normal or negative&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">When the patient first came to our hospital&#44; he presented erythematous plaques with peripheral desquamation&#44; mainly on his lower limbs but also on his upper limbs&#46; Nodules were present beneath the plaques&#46; He also presented edema of the dorsum of the left foot and ankle &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44;<span class="elsevierStyleHsp" style=""></span>A-C&#41;&#46; A biopsy was taken&#44; which was consistent with septal panniculitis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Coinciding with tapering of the dose of prednisone&#44; the patient presented a further outbreak at the same sites as the previous outbreak&#44; with purpuric plaques that spread centrifugally&#44; pain&#44; bilateral ankle edema&#44; and fever&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A further biopsy revealed a neutrophilic infiltrate in the small and medium-sized vessels&#44; with fibrinoid necrosis&#44; and a moderate eosinophilic infiltrate &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#44; A and<span class="elsevierStyleHsp" style=""></span>B&#41;&#46; Based on these findings&#44; we made a diagnosis of PAN&#46; Given the absence of organ involvement&#44; despite the marked elevation of the AFRs and alteration of the patient&#39;s general state of health&#44; we considered this to be cutaneous PAN with an associated systemic inflammatory response&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">After increasing the dose of prednisone to 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d and controlling the acute outbreak&#44; treatment was started with cyclophosphamide and immunoglobulins&#46; However&#44; this did not enable us to reduce the dose of corticosteroids without renewed deterioration&#46; Treatment was therefore commenced with infliximab at a dose of 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; which led to a very good response after the first infusion&#44; with complete normalization of laboratory parameters&#46; The dose of corticosteroids was progressively reduced until their withdrawal&#44; with no further outbreaks of lesions in a year of follow-up&#44; except for a residual livedo &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a><span class="elsevierStyleHsp" style=""></span>C&#41;&#59; during this period the patient continued treatment with infliximab every 8 weeks&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The typical clinical manifestations of cutaneous PAN are characterized by outbreaks of painful nodular lesions that leave a residual livedo&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In the first patient series&#44; dating from 1974&#44; the presence of a starburst pattern was described as a characteristic manifestation of this livedo&#44; and was very similar to that observed in our patient&#44; though we have found no similar descriptions in the recent literature&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Typically&#44; histology reveals a focal panniculitis around affected arteries&#46; However&#44; if the inflammatory infiltrate is very intense&#44; the panniculitis can be so pronounced that it masks the vasculitis&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Three subgroups of cutaneous PAN have been described based on the presentation&#44; laboratory tests&#44; and clinical course&#58; class <span class="elsevierStyleSmallCaps">i</span>&#44; in which the cutaneous manifestations are associated with slightly elevated AFRs&#59; class <span class="elsevierStyleSmallCaps">ii</span>&#44; in which constitutional symptoms are also present&#44; with fever and marked elevation of the AFRs&#59; and class <span class="elsevierStyleSmallCaps">iii</span>&#44; in which the cutaneous form progresses to systemic forms of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> We classified our patient in the second subgroup&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In cutaneous PAN&#44; patients with marked elevation of AFRs are more likely to present inflammatory plaques and edema of the lower limbs&#46; Considering this association as a more severe form of the disease&#44; it has been proposed that the initial management approach should be more aggressive to avoid progression to systemic forms&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Although the use of TNF inhibitors is not uncommon in the systemic forms of PAN&#44; we have found very few reports in the literature in which this treatment has been required to control cutaneous forms &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; we have presented a case of cutaneous PAN associated with a systemic inflammatory response and refractory to conventional treatments&#46; It is essential to suspect this disease in patients with nodules beneath plaques showing centrifugal spread&#44; even if histology does not initially support the diagnosis&#44; particularly if there is an associated intense inflammatory reaction that could hide the vasculitis&#46; Patients with cutaneous PAN with very high AFRs will often require management similar to the systemic forms&#44; and TNF inhibitors are an option&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0065" 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">A&#44; Normal epidermis with lesions in the dermis and subcutaneous cellular tissue&#46; Hematoxylin and eosin&#44; original magnification &#215;4&#46; B&#44; Fibrinoid necrosis and a neutrophilic infiltrate in the medium-sized vessels&#44; with an associated eosinophilic infiltrate&#46; Hematoxylin and eosin&#44; original magnification<span class="elsevierStyleHsp" style=""></span>&#215;20&#46;<span class="elsevierStyleHsp" style=""></span>C&#44; Residual livedo on the legs after starting treatment with infliximab&#46;</p>"
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          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AZA&#44; azathioprine&#59; CsA&#44; ciclosporin&#59; CY&#44; cyclophosphamide&#59; DFPP&#44; double filtration plasmapheresis&#59; ETN&#44; etanercept&#59; IFX&#44; infliximab&#59; IVIG&#44; intravenous immunoglobulin&#59; MTX&#44; methotrexate&#59; NA&#44; not available&#59; OC&#44; oral corticosteroid therapy&#59; PE&#44; plasma exchange&#59; RTX&#44; rituximab&#59; SSZ&#44; sulfasalazine&#59; TAC&#44; tacrolimus&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Authors&#44; Year&#44; and Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&#44; y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">MTX 15<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vega Guti&#233;rrez et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bansal and Houghton&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; CY&#44; MTX&#44; IVIG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg first dose&#44; followed by 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg every 4 wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No response &#40;corticosteroid dependence&#41;&#46; Response to RTX and CY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Zoshima et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&#44; CsA&#44; TAC&#44; CY&#44; AZA&#44; colchicine&#44; PE&#44; DFPP<br>Lamivudine&#44; adefovir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">156&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ETN&#44; 25<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Campanilho-Marques et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; MTX&#44; CY&#44; RTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IFX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Valor et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OC&#44; CY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ETN&#44; 25<span class="elsevierStyleHsp" style=""></span>mg&#47;wk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Resolution&#47;none&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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2021 Diciembre 178 35 213
2021 Noviembre 206 45 251
2021 Octubre 203 62 265
2021 Septiembre 168 35 203
2021 Agosto 159 45 204
2021 Julio 191 31 222
2021 Junio 238 37 275
2021 Mayo 268 51 319
2021 Abril 472 73 545
2021 Marzo 276 39 315
2021 Febrero 197 30 227
2021 Enero 118 25 143
2020 Diciembre 117 18 135
2020 Noviembre 68 23 91
2020 Octubre 63 13 76
2020 Septiembre 73 15 88
2020 Agosto 43 21 64
2020 Julio 51 23 74
2020 Junio 59 35 94
2020 Mayo 29 13 42
2020 Abril 33 18 51
2020 Marzo 33 19 52
2020 Febrero 4 0 4
2020 Enero 4 0 4
2019 Diciembre 8 0 8
2019 Noviembre 4 0 4
2019 Septiembre 8 0 8
2019 Agosto 2 0 2
2019 Julio 6 0 6
2019 Junio 6 0 6
2019 Mayo 2 0 2
2019 Abril 5 0 5
2019 Marzo 4 0 4
2019 Enero 7 0 7
2018 Diciembre 2 0 2
2018 Noviembre 2 0 2
2018 Octubre 4 0 4
2018 Septiembre 4 0 4
2018 Junio 0 1 1
2018 Febrero 27 7 34
2018 Enero 39 8 47
2017 Diciembre 37 16 53
2017 Noviembre 45 11 56
2017 Octubre 108 33 141
2017 Septiembre 4 14 18
2017 Agosto 3 13 16
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