Efficacy of Rituximab in Dermatomyositis and Polymyositis Refractory to Conventional Therapy

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Glucocorticoids (GC) and immunosuppressants such as methotrexate (MTX) and azathioprine (AZA) have been used for treatment with a high percentage of inneficacy.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Different biologic therapies, including rituximab (RTX), a chimeric anti CD20 monoclonal antibody, have occasionally been used. We report a case of refractory dermatomyositis (DM) and polymyositis (PM) intolerant to multiple conventional treatments that later responded to RTX.Clinical CasesCase 1The patient is a 50 year old woman with a history of smoking and depression, diagnosed with DM in 2008 with the presence of a skin rash on the face and arms, proximal limb muscle weakness, elevated muscle enzymes (creatine kinase [CK]: 2982 U/aldolase l: 19.6U/L) and a positive ANA with a titer of 1/640 and negative specific autoantibodies. The electromyogram shows a proximal myopathy of widespread distribution and moderate intensity. She had gastric intolerance and hypertension associated with high doses of GC, and had initially been prescribed prednisone (PD) at 0.5mg/kg/day, with a decrease in the CK values (960U/L) but without improvement of muscle weakness. Subsequent muscle enzymes and the dose of PD with respect to the patient receiving immunosuppressive therapy are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. AZA 150mg/day and MTX 15mg/week were suspended due to gastric intolerance with neither producing significant clinical improvement. Mycophenolate mofetil (MMF) 2g/day was suspended due to inefficiency and worsening clinical and laboratory. After use, the patient was reluctant to undergo an unconventional and unapproved treatment for MII. Because of the appearance of Cushing's syndrome features and cataracts, along with persistent disease activity, in 2010 it was decided to treat the patient with intravenous immunoglobulin (IVIG) at doses of 2g/kg/month for 3 months. There was a good clinical and analytical response but with a rapid relapse after 3 months of suspension. Thus, in February 2011 she was treated with RTX (2 iv infusion cycles of 1g separated by 2 weeks) without other immunosuppressives, showing improvement in muscle weakness and a near normalization of muscle enzymes. This response occured 5 months after the first infusion, but was maintained over time after 9 months without need for retreatment and facilitated a reduction in PD to 10mg/day. During this monitoring no adverse effects related to RTX were detected.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Case 2This patient is a 30-year-old woman with a history of hypertension and morbid obesity, evaluated in 2007 due to proximal limb weakness and elevated muscle enzymes (CK: 4609U/L). PM was diagnosed by the demonstration in the electromyogram of a diffuse proximal myopathy on the muscle biopsy and pathological data consistent with inflammatory myopathy. Initially, PD 1mg/kg/day was employed with a partial response with a decreasing dose to 0.5mg/kg/day after addition of immunosuppressants. These did not prevent several episodes of generalized weakness and severe functional disability requiring treatment with boluses of methylprednisolone (1g/day for 3 consecutive days). The evolution of the values of muscle enzymes and treatment is reflected in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Although MTX (20mg/day) and AZA (150mg/day) was employed, it was impossible to decrease the dose of PD under 30mg/day because of clinical deterioration, so IGIV (2g/kg/month for 3 months) was started, producing clinical and laboratory improvement, but relapsed after 3 months of its termination despite maintaining AZA and MTX associated with GC. In August 2009 it was decided to use RTX (two iv infusions of 1g separated by 2 weeks), maintaining GC, AZA and MTX. At 5 months, there is a great improvement in the proximal weakness and with a decrease in muscle enzymes, which was maintained over time. In January 2011, and after 17 months of the first cycle of RTX, she was given a second course for fear of a relapse, because the patient had to travel abroad for a long time and it was impossible to follow up. With this new dose, she remained in remission for a year and is still in remission, with an almost normalization of CK values (468U/L) and a dose of PD of 5mg/day. No side effects were related to the infusion of RTX or during follow up.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionThe IIM are characterized by the presence of a mild inflammatory infiltrate of the muscle where B lymphocytes seem to have an important role in the pathogenesis, especially in DM. RTX is a monoclonal anti-CD20 antibody used to treat non-Hodgkin lymphoma and rheumatoid arthritis, but is also used in other refractory autoimmune diseases such as SLE, Sjögren's syndrome or vasculitis, producing a profound and sustained depletion of CD20+B cells and without affecting stem cells or plasma cells. Currently, treatment of PM/DM is largely empirical and there is no agreement on what the most optimal therapy is. Initially high-dose GC is used and in cases of resistance to these, or serious extramuscular manifestations, immunosuppressants such as AZA, MTX, cyclosporine A, tacrolimus, MMF or cyclophosphamide<a class="elsevierStyleCrossRef" href="#bib0010">2</a> are added, with around 25% of patients not responding or relapsing even immunosuppresants.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> IVIG has been tested (dose of 1–2g/kg) and shown to act quickly and improve muscle weakness, with few adverse effects but with a high cost and a transitory<a class="elsevierStyleCrossRef" href="#bib0020">4</a> effect. Drugs that inhibit TNF-alpha do not appear to be effective, so are not recommended for use in these diseases, unless other treatment options have failed.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> There are isolated cases or small series published demonstrating the efficacy of RTX in the treatment of refractory IIMs.<a class="elsevierStyleCrossRefs" href="#bib0030">6–9</a> In these publications, a high percentage of patients who respond adequately or do not need a new cycle of early retreatment are those who received IVIG or cyclophosphamide in combination with RTX. There are also differences in the dose of RTX used, with no significant influence on the results (375mg/weekly for 4 doses or cycles of 1g every two weeks for 2 doses), and concomitant therapy used in conjunction with RTX. Garcia et al.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> collected data from 17 patients with IIM which used RTX plus cyclophosphamide IV and where there was an initial improvement in all of them (including 4 in whom respiratory disease was present), requiring a second course of RTX at 11 months only in 5 patients, with subsequent favorable responses in all cases. The publication with the largest number of IIM cases treated with RTX refractory was published by Couderc et al.,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> based in the French AIR (Auto-Immunity and Rituximab) trial. They obtained a favorable response in 16 of the 30 patients with refractory IIM treated with RTX, with an average efficiency of 15 months and a decrease in the values of CPK and dose of GC in most of them. The dose used was 1g×2 doses 2 weeks apart in 83% of cases and 375mg/m2 weekly×4 weeks in 17%. Most received concurrent GC and immunosuppressive treatment (28 and 21 patients, respectively) and of 10 patients a favorable response was seen in 8 of them.We expose the effectiveness of RTX in refractory DM and PM (to immunosuppresants) but without the simultaneous use of IVIG or cyclophosphamide and allowing lower doses of GC without relapse. We used a dose of RTX similar to that employed for rheumatoid arthritis by checking their effectiveness in other publications. In both cases, the response to RTX was late (5 months or so) but, unlike the response induced by IVIG, remained constant for at least 1 year after the first cycle.Regarding the possible side effects of RTX, there are several, the most frequent being infusional reactions and other hematological disorders as well as infections (upper respiratory, urinary or skin) or severe and progressive multifocal leukoencephalopathy. In our 2 cases, administration of RTX was well tolerated and not accompanied by adverse effects.ConclusionBased on the cases presented and previously published experiences, we believe that RTX is a valid alternative to consider in the treatment of DM and PM refractory to conventional treatment, even without other simultaneous immunosuppressive drugs. The dose of RTX and the optimal treatment for remission should be established.Ethical disclosuresProtection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation.Confidentiality of Data. The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.Right to privacy and informed consent. The authors have obtained the informed consent of the patients and /or subjects mentioned in the article. The author for correspondence is in possession of this document.DisclosuresThe authors have no disclosures to make." 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Eficacia de rituximab en dermatomiositis y polimiositis refractarias al tratamiento convencional. Reumatol Clin. 2012. http://dx.doi.org/10.1016/j.reuma.2012.02.007." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "GC: glucocorticoids; AZA: azathioprine; MTX: methotrexate; MMF: mycophenolate mofetil; IGIV: intravenous immunoglobulin; RTX: rituximab; CK: creatinkynase (normal: <250); aldolase (normal: <7); AST: aspartate aminotransferase (normal: 10–40); ALT: alanine aminotransferase (normal: 10–40); PD: prednisone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Initial diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">GC \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">AZA \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">MMF \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">IGIV \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">3 months after IGIV \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">1.st RTX infusion \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">3 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">6 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">9 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">CK, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2982 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">960 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">902 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">728 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1737 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">361 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1632 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2762 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1253 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">344 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">339 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Aldolase, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.5 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AST, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">ALT, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">PD, mg/day \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab176523.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Case 1: Progression of Muscles Enzymes and Treatment." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "GC: glucocorticoids; AZA: azathioprine; MTX: methotrexate; IGIV: intravenous immunoglobulin; RTX: rituximab; CK: creatinkynase (normal: <250); AST: aspartate aminotransferase (normal: 10–40); ALT: alanine aminotransferase (normal: 10–40); PD: prednisone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Initial diagnosis \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">GC \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">AZA+MTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">+IGIV \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">3 months after IGIV \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">1st RTX infusion \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">3 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">6 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">15 months after RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">2nd cycle of RTX \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">9 months after 2nd cycle RTX \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><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">CK, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4609 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1024 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">331 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1316 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1366 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1101 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">737 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">468 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">616 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">593 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">AST, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">ALT, U/L \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">152 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">PD, mg/day \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab176522.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Case 2: Progression of Muscle Enzymes and Treatment." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapy of polymyositis and 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Case report

Efficacy of Rituximab in Dermatomyositis and Polymyositis Refractory to Conventional Therapy

Eficacia de rituximab en dermatomiositis y polimiositis refractarias al tratamiento convencional

Simón Ángel Sánchez-Fernández

Corresponding author

simon.sanchez.fernandez@gmail.com

Corresponding author.

, José Antonio Carrasco Fernández, Luisa Marena Rojas Vargas

Sección de Reumatología, Hospital La Mancha Centro, Alcázar de San Juan, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Idiopathic inflammatory myopathies &#40;IIM&#41; are connective tissue diseases of unknown etiology which primarily affect skeletal muscle&#44; skin and other internal organs&#46; Glucocorticoids &#40;GC&#41; and immunosuppressants such as methotrexate &#40;MTX&#41; and azathioprine &#40;AZA&#41; have been used for treatment with a high percentage of inneficacy&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Different biologic therapies&#44; including rituximab &#40;RTX&#41;&#44; a chimeric anti CD20 monoclonal antibody&#44; have occasionally been used&#46; We report a case of refractory dermatomyositis &#40;DM&#41; and polymyositis &#40;PM&#41; intolerant to multiple conventional treatments that later responded to RTX&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Clinical Cases</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case 1</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient is a 50 year old woman with a history of smoking and depression&#44; diagnosed with DM in 2008 with the presence of a skin rash on the face and arms&#44; proximal limb muscle weakness&#44; elevated muscle enzymes &#40;creatine kinase &#91;CK&#93;&#58; 2982 U&#47;aldolase l&#58; 19&#46;6<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and a positive ANA with a titer of 1&#47;640 and negative specific autoantibodies&#46; The electromyogram shows a proximal myopathy of widespread distribution and moderate intensity&#46; She had gastric intolerance and hypertension associated with high doses of GC&#44; and had initially been prescribed prednisone &#40;PD&#41; at 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#44; with a decrease in the CK values &#40;960<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; but without improvement of muscle weakness&#46; Subsequent muscle enzymes and the dose of PD with respect to the patient receiving immunosuppressive therapy are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; AZA 150<span class="elsevierStyleHsp" style=""></span>mg&#47;day and MTX 15<span class="elsevierStyleHsp" style=""></span>mg&#47;week were suspended due to gastric intolerance with neither producing significant clinical improvement&#46; Mycophenolate mofetil &#40;MMF&#41; 2<span class="elsevierStyleHsp" style=""></span>g&#47;day was suspended due to inefficiency and worsening clinical and laboratory&#46; After use&#44; the patient was reluctant to undergo an unconventional and unapproved treatment for MII&#46; Because of the appearance of Cushing&#39;s syndrome features and cataracts&#44; along with persistent disease activity&#44; in 2010 it was decided to treat the patient with intravenous immunoglobulin &#40;IVIG&#41; at doses of 2<span class="elsevierStyleHsp" style=""></span>g&#47;kg&#47;month for 3 months&#46; There was a good clinical and analytical response but with a rapid relapse after 3 months of suspension&#46; Thus&#44; in February 2011 she was treated with RTX &#40;2 iv infusion cycles of 1<span class="elsevierStyleHsp" style=""></span>g separated by 2 weeks&#41; without other immunosuppressives&#44; showing improvement in muscle weakness and a near normalization of muscle enzymes&#46; This response occured 5 months after the first infusion&#44; but was maintained over time after 9 months without need for retreatment and facilitated a reduction in PD to 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; During this monitoring no adverse effects related to RTX were detected&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case 2</span><p id="par0015" class="elsevierStylePara elsevierViewall">This patient is a 30-year-old woman with a history of hypertension and morbid obesity&#44; evaluated in 2007 due to proximal limb weakness and elevated muscle enzymes &#40;CK&#58; 4609<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41;&#46; PM was diagnosed by the demonstration in the electromyogram of a diffuse proximal myopathy on the muscle biopsy and pathological data consistent with inflammatory myopathy&#46; Initially&#44; PD 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day was employed with a partial response with a decreasing dose to 0&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day after addition of immunosuppressants&#46; These did not prevent several episodes of generalized weakness and severe functional disability requiring treatment with boluses of methylprednisolone &#40;1<span class="elsevierStyleHsp" style=""></span>g&#47;day for 3 consecutive days&#41;&#46; The evolution of the values of muscle enzymes and treatment is reflected in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Although MTX &#40;20<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; and AZA &#40;150<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; was employed&#44; it was impossible to decrease the dose of PD under 30<span class="elsevierStyleHsp" style=""></span>mg&#47;day because of clinical deterioration&#44; so IGIV &#40;2<span class="elsevierStyleHsp" style=""></span>g<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#47;</span>kg&#47;month for 3 months&#41; was started&#44; producing clinical and laboratory improvement&#44; but relapsed after 3 months of its termination despite maintaining AZA and MTX associated with GC&#46; In August 2009 it was decided to use RTX &#40;two iv infusions of 1<span class="elsevierStyleHsp" style=""></span>g separated by 2 weeks&#41;&#44; maintaining GC&#44; AZA and MTX&#46; At 5 months&#44; there is a great improvement in the proximal weakness and with a decrease in muscle enzymes&#44; which was maintained over time&#46; In January 2011&#44; and after 17 months of the first cycle of RTX&#44; she was given a second course for fear of a relapse&#44; because the patient had to travel abroad for a long time and it was impossible to follow up&#46; With this new dose&#44; she remained in remission for a year and is still in remission&#44; with an almost normalization of CK values &#40;468<span class="elsevierStyleHsp" style=""></span>U&#47;L&#41; and a dose of PD of 5<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; No side effects were related to the infusion of RTX or during follow up&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">The IIM are characterized by the presence of a mild inflammatory infiltrate of the muscle where B lymphocytes seem to have an important role in the pathogenesis&#44; especially in DM&#46; RTX is a monoclonal anti-CD20 antibody used to treat non-Hodgkin lymphoma and rheumatoid arthritis&#44; but is also used in other refractory autoimmune diseases such as SLE&#44; Sj&#246;gren&#39;s syndrome or vasculitis&#44; producing a profound and sustained depletion of CD20&#43;B cells and without affecting stem cells or plasma cells&#46; Currently&#44; treatment of PM&#47;DM is largely empirical and there is no agreement on what the most optimal therapy is&#46; Initially high-dose GC is used and in cases of resistance to these&#44; or serious extramuscular manifestations&#44; immunosuppressants such as AZA&#44; MTX&#44; cyclosporine A&#44; tacrolimus&#44; MMF or cyclophosphamide<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> are added&#44; with around 25&#37; of patients not responding or relapsing even immunosuppresants&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> IVIG has been tested &#40;dose of 1&#8211;2<span class="elsevierStyleHsp" style=""></span>g&#47;kg&#41; and shown to act quickly and improve muscle weakness&#44; with few adverse effects but with a high cost and a transitory<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> effect&#46; Drugs that inhibit TNF-alpha do not appear to be effective&#44; so are not recommended for use in these diseases&#44; unless other treatment options have failed&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> There are isolated cases or small series published demonstrating the efficacy of RTX in the treatment of refractory IIMs&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;9</span></a> In these publications&#44; a high percentage of patients who respond adequately or do not need a new cycle of early retreatment are those who received IVIG or cyclophosphamide in combination with RTX&#46; There are also differences in the dose of RTX used&#44; with no significant influence on the results &#40;375<span class="elsevierStyleHsp" style=""></span>mg&#47;weekly for 4 doses or cycles of 1<span class="elsevierStyleHsp" style=""></span>g every two weeks for 2 doses&#41;&#44; and concomitant therapy used in conjunction with RTX&#46; Garcia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> collected data from 17 patients with IIM which used RTX plus cyclophosphamide IV and where there was an initial improvement in all of them &#40;including 4 in whom respiratory disease was present&#41;&#44; requiring a second course of RTX at 11 months only in 5 patients&#44; with subsequent favorable responses in all cases&#46; The publication with the largest number of IIM cases treated with RTX refractory was published by Couderc et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> based in the French AIR &#40;Auto-Immunity and Rituximab&#41; trial&#46; They obtained a favorable response in 16 of the 30 patients with refractory IIM treated with RTX&#44; with an average efficiency of 15 months and a decrease in the values of CPK and dose of GC in most of them&#46; The dose used was 1<span class="elsevierStyleHsp" style=""></span>g&#215;2 doses 2 weeks apart in 83&#37; of cases and 375<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> weekly&#215;4 weeks in 17&#37;&#46; Most received concurrent GC and immunosuppressive treatment &#40;28 and 21 patients&#44; respectively&#41; and of 10 patients a favorable response was seen in 8 of them&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We expose the effectiveness of RTX in refractory DM and PM &#40;to immunosuppresants&#41; but without the simultaneous use of IVIG or cyclophosphamide and allowing lower doses of GC without relapse&#46; We used a dose of RTX similar to that employed for rheumatoid arthritis by checking their effectiveness in other publications&#46; In both cases&#44; the response to RTX was late &#40;5 months or so&#41; but&#44; unlike the response induced by IVIG&#44; remained constant for at least 1 year after the first cycle&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Regarding the possible side effects of RTX&#44; there are several&#44; the most frequent being infusional reactions and other hematological disorders as well as infections &#40;upper respiratory&#44; urinary or skin&#41; or severe and progressive multifocal leukoencephalopathy&#46; In our 2 cases&#44; administration of RTX was well tolerated and not accompanied by adverse effects&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0035" class="elsevierStylePara elsevierViewall">Based on the cases presented and previously published experiences&#44; we believe that RTX is a valid alternative to consider in the treatment of DM and PM refractory to conventional treatment&#44; even without other simultaneous immunosuppressive drugs&#46; The dose of RTX and the optimal treatment for remission should be established&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Protection of human and animal subjects&#46;</span> The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Confidentiality of Data&#46;</span> The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study&#46;<span class="elsevierStyleVsp" style="height:0.5px"></span></p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Right to privacy and informed consent&#46;</span> The authors have obtained the informed consent of the patients and &#47;or subjects mentioned in the article&#46; The author for correspondence is in possession of this document&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Disclosures</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have no disclosures to make&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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        0 => array:2 [
          "identificador" => "xres90921"
          "titulo" => "Abstract"
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        1 => array:2 [
          "identificador" => "xpalclavsec78145"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "xres90920"
          "titulo" => "Resumen"
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec78144"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Clinical Cases"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Case 1"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Case 2"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Discussion"
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conclusion"
        ]
        8 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Ethical disclosures"
        ]
        9 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Disclosures"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2012-01-11"
    "fechaAceptado" => "2012-02-23"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec78145"
          "palabras" => array:4 [
            0 => "Dermatomyositis"
            1 => "Polymyositis"
            2 => "Refractory"
            3 => "Rituximab"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec78144"
          "palabras" => array:4 [
            0 => "Dermatomiositis"
            1 => "Polimiositis"
            2 => "Refractario"
            3 => "Rituximab"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies&#44; which present a response after treatment with rituximab&#44; enabling steroid dose reduction and a prolonged remission&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se presentan un caso de dermatomiositis y otro de polimiositis refractarias a varios inmunosupresores convencionales y con respuesta a tratamiento con rituximab&#44; con el que se posibilita la disminuci&#243;n de dosis de corticoide y se mantiene a la enfermedad en remisi&#243;n durante un largo periodo&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; S&#225;nchez-Fern&#225;ndez S&#193;&#44; et al&#46; Eficacia de rituximab en dermatomiositis y polimiositis refractarias al tratamiento convencional&#46; Reumatol Clin&#46; 2012&#46; http&#58;&#47;&#47;dx&#46;doi&#46;org&#47;10&#46;1016&#47;j&#46;reuma&#46;2012&#46;02&#46;007&#46;</p>"
      ]
    ]
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        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">GC&#58; glucocorticoids&#59; AZA&#58; azathioprine&#59; MTX&#58; methotrexate&#59; MMF&#58; mycophenolate mofetil&#59; IGIV&#58; intravenous immunoglobulin&#59; RTX&#58; rituximab&#59; CK&#58; creatinkynase &#40;normal&#58; &#60;250&#41;&#59; aldolase &#40;normal&#58; &#60;7&#41;&#59; AST&#58; aspartate aminotransferase &#40;normal&#58; 10&#8211;40&#41;&#59; ALT&#58; alanine aminotransferase &#40;normal&#58; 10&#8211;40&#41;&#59; PD&#58; prednisone&#46;</p>"
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Initial diagnosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">GC&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">AZA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">IGIV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">9 months after RTX&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">CK&#44; U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">902&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">728&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1737&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">361&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1632&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2762&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1253&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">344&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">339&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Aldolase&#44; U&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">18&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \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">AST&#44; U&#47;L&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="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&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="char" valign="\n
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                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">ALT&#44; U&#47;L&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&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="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">28&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="char" valign="\n
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                  \t\t\t\t">48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&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="char" valign="\n
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                  \t\t\t\t">53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">PD&#44; mg&#47;day&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&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
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                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab176523.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Case 1&#58; Progression of Muscles Enzymes and Treatment&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">GC&#58; glucocorticoids&#59; AZA&#58; azathioprine&#59; MTX&#58; methotrexate&#59; IGIV&#58; intravenous immunoglobulin&#59; RTX&#58; rituximab&#59; CK&#58; creatinkynase &#40;normal&#58; &#60;250&#41;&#59; AST&#58; aspartate aminotransferase &#40;normal&#58; 10&#8211;40&#41;&#59; ALT&#58; alanine aminotransferase &#40;normal&#58; 10&#8211;40&#41;&#59; PD&#58; prednisone&#46;</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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Initial diagnosis&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">GC&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">AZA&#43;MTX&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">&#43;IGIV&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">3 months after IGIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">1st RTX infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">3 months after RTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">6 months after RTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">15 months after RTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">2nd cycle of RTX&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">9 months after 2nd cycle RTX&nbsp;\t\t\t\t\t\t\n
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                  \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">CK&#44; U&#47;L&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4609&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1024&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">331&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1316&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1366&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1101&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">737&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">468&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="char" valign="\n
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2012.07.006

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	15	8	23
2024 October	142	49	191
2024 September	169	17	186
2024 August	154	26	180
2024 July	220	40	260
2024 June	156	31	187
2024 May	135	42	177
2024 April	137	24	161
2024 March	151	31	182
2024 February	103	29	132
2024 January	121	27	148
2023 December	95	36	131
2023 November	115	30	145
2023 October	126	43	169
2023 September	141	49	190
2023 August	122	24	146
2023 July	88	28	116
2023 June	88	19	107
2023 May	42	16	58
2023 April	58	4	62
2023 March	140	28	168
2023 February	104	34	138
2023 January	109	26	135
2022 December	154	35	189
2022 November	134	38	172
2022 October	134	45	179
2022 September	121	44	165
2022 August	109	44	153
2022 July	101	42	143
2022 June	128	41	169
2022 May	109	59	168
2022 April	130	52	182
2022 March	162	56	218
2022 February	142	38	180
2022 January	159	41	200
2021 December	107	57	164
2021 November	131	46	177
2021 October	119	76	195
2021 September	93	51	144
2021 August	90	56	146
2021 July	79	46	125
2021 June	139	60	199
2021 May	152	33	185
2021 April	271	77	348
2021 March	184	58	242
2021 February	103	24	127
2021 January	110	30	140
2020 December	90	29	119
2020 November	86	25	111
2020 October	57	11	68
2020 September	60	18	78
2020 August	60	27	87
2020 July	55	19	74
2020 June	40	24	64
2020 May	59	15	74
2020 April	51	17	68
2020 March	21	10	31
2020 February	2	0	2
2019 July	0	2	2
2019 May	1	0	1
2019 January	1	0	1
2018 May	6	4	10
2018 April	77	10	87
2018 March	108	10	118
2018 February	49	6	55
2018 January	49	6	55
2017 December	72	5	77
2017 November	75	7	82
2017 October	76	12	88
2017 September	88	17	105
2017 August	117	20	137
2017 July	111	7	118
2017 June	106	19	125
2017 May	125	23	148
2017 April	94	14	108
2017 March	92	53	145
2017 February	78	16	94
2017 January	83	13	96
2016 December	122	17	139
2016 November	131	17	148
2016 October	158	27	185
2016 September	249	19	268
2016 August	146	9	155
2016 July	94	21	115
2016 May	0	8	8
2016 February	1	0	1
2016 January	3	25	28
2015 December	2	0	2
2015 November	1	0	1
2015 October	3	12	15
2015 September	1	0	1
2015 August	1	0	1
2015 July	53	7	60
2015 June	79	12	91
2015 May	144	13	157
2015 April	114	14	128
2015 March	87	12	99
2015 February	102	8	110
2015 January	85	9	94
2014 December	78	18	96
2014 November	80	9	89
2014 October	67	12	79
2014 September	66	16	82
2014 August	74	10	84
2014 July	62	17	79
2014 June	117	22	139
2014 May	95	20	115
2014 April	82	14	96
2014 March	91	19	110
2014 February	64	27	91
2014 January	73	20	93
2013 December	66	19	85
2013 November	59	13	72
2013 October	74	17	91
2013 September	59	21	80
2013 August	69	30	99
2013 July	53	19	72
2013 June	49	27	76
2013 May	64	39	103
2013 April	33	18	51

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