Case report
Necrotizing fasciitis in a patient receiving tocilizumab for rheumatoid arthritis – Case report
Fascitis necrosante en un paciente bajo tocilizumab para la artritis reumatoide. Presentación de un caso
Diana Rosa-Gonçalves
, Miguel Bernardes, Lúcia Costa
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Rheumatology Department, Centro Hospitalar São João, Portugal
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Presentación de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 832 "Ancho" => 1500 "Tamanyo" => 123152 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evolution of skin lesions at first five days of internment: áreas of extensive skin detachment in the context of ruptura of blisters and severe exudation and necrotic áreas.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Necrotizing fasciitis (NF) is a rare severe infection affecting subcutaneous tissue and superficial fascia associated with considerable mortality (70–80%).<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1–3</span></a> The infections are the most feared adverse events of tocilizumab (TOC); there are few published pos-marketing data.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A case report of NF is presented with a published cases review through PubMed database and several European Biologics Registers.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 66-year-old Caucasian woman with a seropositive RA presented with sudden onset of severe and progressive forearm and elbow pain with 3 days of evolution. She denied fever and history of trauma or animal bite. Since fourteen years ago, she has been consecutively treated with methotrexate (up to 20<span class="elsevierStyleHsp" style=""></span>mg/week), etanercept (50<span class="elsevierStyleHsp" style=""></span>mg weekly) and adalimumab (40<span class="elsevierStyleHsp" style=""></span>mg fortnightly), which were discontinued owing to lack of efficacy. For three years, she has been treated with prednisolone (7.5<span class="elsevierStyleHsp" style=""></span>mg/day), leflunomide (LEF) (10<span class="elsevierStyleHsp" style=""></span>mg/day) and TOC (8<span class="elsevierStyleHsp" style=""></span>mg/kg intravenous (iv) every 4 weeks). The prior medical history was significant for bacterial osteomyelitis (foot fifth digit) under TOC monotherapy for a year. Vital signs were as follow: pulse, 86beats/min; blood pressure, 135/72<span class="elsevierStyleHsp" style=""></span>mmHg; body temperature, 36.8<span class="elsevierStyleHsp" style=""></span>°C. Had active synovitis in metacarpophalangeal, interphalangeal and wrist joints. Left upper limb presented diffusely oedematous with a slight erythematous rash and increased temperature. Laboratory tests were as follow: hemoglobin 12.3<span class="elsevierStyleHsp" style=""></span>g/dl; white blood cell (WBC) count 11.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>109/l (neutrophils 10.6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>109/l); platelets 149<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>109/l; C-reactive protein (CRP) 74.6<span class="elsevierStyleHsp" style=""></span>mg/L; creatinine 1.51<span class="elsevierStyleHsp" style=""></span>mg/dl; sodium 138<span class="elsevierStyleHsp" style=""></span>mEq/l and glucose 91<span class="elsevierStyleHsp" style=""></span>mg/dl. Arteriovenous Doppler ultrasound excluded venous thrombosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Three days later, erythrocyte sedimentation rate was 58<span class="elsevierStyleHsp" style=""></span>mm and CRP 188.3<span class="elsevierStyleHsp" style=""></span>mg/L. Differential diagnosis included cellulitis and septic arthritis. Immunosuppressants drugs were discontinued, cholestyramine and empiric antibiotic therapy (vancomycin and imipenem) were initiated. Magnetic resonance showed peri-aponeurosis and muscle edema (especially deltoid muscle), signs of cellulitis, without organized collections. At day 5 of treatment, lesions rapidly progressed to extensive areas of skin detachment and necrosis with severe exudation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). She had now periodic fever. <span class="elsevierStyleItalic">Enterobacter aerogenes</span>, <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and <span class="elsevierStyleItalic">Stenotrophomonas maltophilia</span> were identified in the skin; blood cultures were negative. Surgical debridement with subsequent partial skin graft and a twenty-days period of antibiotics led to progressive improvement. She was discharged at day 39.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">After one-year follow-up there was no recurrence of infections. She is under hydroxychloroquine (400<span class="elsevierStyleHsp" style=""></span>mg/day) and prednisolone (7.5<span class="elsevierStyleHsp" style=""></span>mg/day). Methotrexate was added but soon discontinued due to oral mucositis. TOC was permanently withdrawn.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Literature review and discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">We identified three case reports of NF in RA patients receiving TOC<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3–5</span></a> and three under TNF antagonists<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6–8</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Published rates of serious skin and soft tissue infections in RA patients vary widely between different European Biologics Registers, from 12–18 per 1000 patient-years in the British register to 37–76 per 1000 patient-years in German register.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> Results from British register showed that the majority were cellulitis (227/309; 73%) and only four cases were NF (all with anti-TNF).<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">A German cohort study concluded that longer disease duration, history of severe infections, previous exposure to multiple DMARDs and concomitant treatments with LEF, prednisone or proton-pump inhibitor increase the risk of infections under TOC. This is our patient profile. In the TOWARD study, infections were more prevalent among patients receiving TOC and DMARDs simultaneously; however, there was no explicitly assigned association to LEF.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> Thus, we cannot overlooked that our patient was under LEF and glucocorticoids and we should attribute the adverse event to their association with TOC rather than to TOC alone. TOC contribution remains speculative and causality can neither be asserted nor ruled out with certainty. So, we believe that is important to report such infections in the post-marketing surveillance.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, physician should keep in mind that infections may mimic a disease flare and the absence of fever does not exclude serious infections in RA patients under biologics.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animals subjects</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors state that no human or animal experiments have been performed for this investigation.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors state that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have received written consent from the patients and/or subjects mentioned in the article. The author for correspondence must be in possession of this document.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">All authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1016825" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec975627" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1016824" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec975626" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Literature review and discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animals subjects" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-08-03" "fechaAceptado" => "2016-10-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec975627" "palabras" => array:6 [ 0 => "Rheumatoid arthritis" 1 => "Infection" 2 => "Necrotizing fasciitis" 3 => "Skin" 4 => "Tocilizumab" 5 => "Tumor necrosis factor antagonists" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec975626" "palabras" => array:6 [ 0 => "Artritis reumatoide" 1 => "Infección" 2 => "Fascitis necrosante" 3 => "Piel" 4 => "Tocilizumab" 5 => "Antagonistas del factor de necrosis tumoral alfa" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We present a case of necrotizing fasciitis in a 66-year-old Caucasian woman with rheumatoid arthritis receiving tocilizumab, and provide a review of published cases. The patient exhibited no systemic symptoms and discreet cutaneous inflammatory signals at presentation. She was successfully treated with broad-spectrum empiric antibiotic therapy and surgical debridement.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Presentamos un caso de fascitis necrosante en una mujer caucásica de 66 años de edad con artritis reumatoide en tratamiento con tocilizumab y se ha realizado una revisión de casos publicados. La paciente ha presentado falta de síntomas sistémicos y señales inflamatorias cutáneas discretas. Ha sido tratada con éxito con terapia antibiótica empírica de amplio espectro y desbridamiento quirúrgico.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 832 "Ancho" => 1500 "Tamanyo" => 123152 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evolution of skin lesions at first five days of internment: áreas of extensive skin detachment in the context of ruptura of blisters and severe exudation and necrotic áreas.</p>" ] ] 1 => 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:2 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AZA, azathioprine; cDMARD, classic disease-modifying antirheumatic drugs; CCT, corticotherapy; CRP, C-reactive protein; CT, computerized tomography; DIC, disseminated intravascular coagulation; DM, diabetes mellitus; F, female; HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulin; LEFL, leflunomide; MRI, magnetic resonance imaging; M, male; MTX, methotrexate; RA, rheumatoid arthritis; SSZ, sulfasalazine; TCZ, tocilizumab; WBC, white blood cell; ?, unknown.</p>" "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Case (reference) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> \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">Biological \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TCZ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TCZ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">TCZ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Etanercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Infliximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Etanercept \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">Gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \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">RA duration (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \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">TNFα blockers/TCZ therapy duration (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \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">Current cDMARD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AZA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">i.m MTX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">Previous DMARD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MTX, HCQ, adalimumab, etanercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MTX, SSZ, tracolimus, infliximab, etanercept \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SSZ, AZA, cyclosporin, i.m. gold, MTX \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gold, HCQ, SSZ, MTX, AZA, LEFL \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">CCTs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">Previous infection under biologics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">Area \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pectoral region<br>Shoulder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hand, Forearm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Shoulder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thigh \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lower limb \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">Fever at apresentation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">WBC (/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22,100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14,820 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \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">Neutrophils (/mm<span class="elsevierStyleSup">3</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4900 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19,669 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Raised \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13,990 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \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">CRP (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Raised \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \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">Fasciitis in CT/MRI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/not done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not done/not done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/not done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/not done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not done/not done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not done/not done \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">Isolated agents in skin swabs/blood cultures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Group A Streptococcus (pyogenes)/None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Group A Streptococcus/none \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Group A Streptococcus/none \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Group A Streptococcus/Group A Streptococcus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Group A Streptococcus/Group A Streptococcus \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">Treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gentamicin, penicillin, clindamycin, (+IVIGs<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>hydrocortisone) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Penicillin G, meropenem \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cefotaxime, metronidazol, vancomycin, ciprofloxacin; clindamycin, ciprofloxacin, flucloxacillin, benzylpenicillin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">DIC treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clindamicina, vancomicina, levofloxacina, IVIGs \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">Surgical debridement/skin graft \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/no \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">Sepsis/death \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No/no \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (DIC)/yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1723935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Characterization of reported cases of necrotizing fasciitis with tocilizumab and TNFα blockers.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical safety of tocilizumab in rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. 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| año/Mes | Html | Total | |
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| 2018 Septiembre | 1 | 0 | 1 |
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| 2018 Mayo | 3 | 2 | 5 |
| 2018 Abril | 2 | 11 | 13 |
| 2018 Marzo | 0 | 15 | 15 |
| 2018 Febrero | 0 | 11 | 11 |
| 2018 Enero | 0 | 14 | 14 |
| 2017 Diciembre | 0 | 10 | 10 |
| 2017 Noviembre | 0 | 8 | 8 |
| 2017 Octubre | 0 | 11 | 11 |
| 2017 Septiembre | 0 | 12 | 12 |
| 2017 Agosto | 0 | 9 | 9 |
| 2017 Julio | 0 | 22 | 22 |
| 2017 Junio | 0 | 17 | 17 |
| 2017 Mayo | 0 | 27 | 27 |
| 2017 Abril | 0 | 25 | 25 |
| 2017 Marzo | 0 | 30 | 30 |
| 2017 Febrero | 0 | 32 | 32 |
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