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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Adult Still&#39;s disease is an entity of uncommon autoimmune origin&#44; characterized from the physiopathogenic point of view by increased production of inflammatory cytokines&#44; mainly tumor necrosis factor&#44; interleukin 1 &#40;IL-1&#41; and IL-6&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Recently&#44; we employed tocilizumab treatment with a good response in 2 patients with adult Still&#39;s disease&#44; both with failure to respond to treatment with glucocorticoids and nonbiological disease modifying drugs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Patient 1 is a 50-year-old woman&#44; diagnosed with adult Still&#39;s disease in 2003 due to daily evening fever &#62;39<span class="elsevierStyleHsp" style=""></span>&#176;<span class="elsevierStyleSmallCaps">C&#44;</span> symmetric polyarthritis&#44; generalized myalgia&#44; evanescent salmon rash on the trunk and limbs&#44; together with elevated acute phase reactants and increased ferritin level &#40;1700<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; Other autoimmune&#44; infectious and neoplastic causes were ruled out&#46; In a span of eight years&#44; she received nonsteroidal anti-inflammatory drugs&#44; glucocorticoids in varying doses&#44; antimalarials&#44; sulfasalazine&#44; methotrexate&#44; leflunomide&#44; azathioprine&#44; rituximab&#44; etanercept and infliximab&#44; with partial response and multiple relapses&#46; In March 2011&#44; due to the persistence of fever&#44; polyarthritis and elevated acute phase reactants&#44; treatment was started with tocilizumab 8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;month methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg&#47;week and prednisone 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#46; A good response was observed after 4 weeks of treatment&#44; which persists to date with improvement of general condition of the skin and joints&#44; no fever and improvement of acute phase reactants&#46; Dyslipidemia occurred as an adverse event&#44; which warranted special treatment&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patient 2 is a 53-year-old woman with a history of breast cancer in 1997&#44; treated and without tumor activity&#46; In October 2009 she presented maculopapular rash&#44; daily fever&#44; arthritis&#44; myalgias&#44; and weight loss of 11<span class="elsevierStyleHsp" style=""></span>kg in 4 months&#46; She also had hepatosplenomegaly and generalized lymphadenopathy&#44; normochromic normocytic anemia&#44; neutrophilia&#44; thrombocytosis&#44; erythrocyte sedimentation rate &#40;ESR&#41; 67<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#44; C-reactive protein &#40;CRP&#41; 84<span class="elsevierStyleHsp" style=""></span>mg&#47;l and ferritin 1900<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Myeloproliferative and infectious processes were ruled out&#46; Still&#39;s disease was diagnosed and she received treatment with methotrexate 20<span class="elsevierStyleHsp" style=""></span>mg&#47;week and prednisone in an initial dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; with gradual reduction to 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day in 4 months&#44; persisting with joint pain&#44; myalgia&#44; rash and malaise&#46; We added tocilizumab treatment 8<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;month&#44; with a good clinical response and significant improvement in acute phase reactants&#46; So far&#44; she has had no adverse events and is under close surveillance due to the history of neoplasia&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Both cases presented had adult onset Still&#39;s disease treated with tocilizumab and a very good response to treatment&#44; almost from the first week&#44; improvement in the clinical manifestations of fever&#44; rash and arthropathy&#44; and a frank and rapid reduction in the acute phase reactants &#40;WBC&#44; CRP&#44; ESR&#41;&#46; This is similar to the cases reported in the literature that relate very significant improvement of clinical manifestations and acute inflammatory response even in refractory patients with multiple prior therapies&#46; As in the case of our patients&#44; the majority of reports describe that the response is maintained and adverse effects&#44; particularly dyslipidemia&#44; improve with specific treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;11</span></a> Although the data available to date are still limited due to the rarity of the disease and limited availability of anti-IL-6 treatment&#44; it seems clear that the use of tocilizumab represents a good alternative for the treatment of this disease&#44; which can be chronic and potentially disabling&#46; Our patients are the first to be reported in Latin American literature&#46;</p></span>"
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Journal Information
Vol. 10. Issue 3.
Pages 199-200 (May - June 2014)
Vol. 10. Issue 3.
Pages 199-200 (May - June 2014)
Letter to the Editor
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Efficacy of Tocilizumab in Refractory Adult-Onset Still's Disease; Report of 2 Cases
Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos
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Lilia Andrade-Ortega
Corresponding author
liliaandrade@prodigy.net.mx

Corresponding author.
, Fedra Irazoque-Palazuelos, Sandra Muñoz-López, Victor M. Rosales-Don Pablo
Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City, Mexico
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Dear Editor:

Adult Still's disease is an entity of uncommon autoimmune origin, characterized from the physiopathogenic point of view by increased production of inflammatory cytokines, mainly tumor necrosis factor, interleukin 1 (IL-1) and IL-6.1,2 Recently, we employed tocilizumab treatment with a good response in 2 patients with adult Still's disease, both with failure to respond to treatment with glucocorticoids and nonbiological disease modifying drugs.

Patient 1 is a 50-year-old woman, diagnosed with adult Still's disease in 2003 due to daily evening fever >39°C, symmetric polyarthritis, generalized myalgia, evanescent salmon rash on the trunk and limbs, together with elevated acute phase reactants and increased ferritin level (1700ng/ml). Other autoimmune, infectious and neoplastic causes were ruled out. In a span of eight years, she received nonsteroidal anti-inflammatory drugs, glucocorticoids in varying doses, antimalarials, sulfasalazine, methotrexate, leflunomide, azathioprine, rituximab, etanercept and infliximab, with partial response and multiple relapses. In March 2011, due to the persistence of fever, polyarthritis and elevated acute phase reactants, treatment was started with tocilizumab 8mg/kg/month methotrexate 15mg/week and prednisone 15mg/day. A good response was observed after 4 weeks of treatment, which persists to date with improvement of general condition of the skin and joints, no fever and improvement of acute phase reactants. Dyslipidemia occurred as an adverse event, which warranted special treatment.

Patient 2 is a 53-year-old woman with a history of breast cancer in 1997, treated and without tumor activity. In October 2009 she presented maculopapular rash, daily fever, arthritis, myalgias, and weight loss of 11kg in 4 months. She also had hepatosplenomegaly and generalized lymphadenopathy, normochromic normocytic anemia, neutrophilia, thrombocytosis, erythrocyte sedimentation rate (ESR) 67mm/h, C-reactive protein (CRP) 84mg/l and ferritin 1900ng/ml. Myeloproliferative and infectious processes were ruled out. Still's disease was diagnosed and she received treatment with methotrexate 20mg/week and prednisone in an initial dose of 1mg/kg, with gradual reduction to 20mg/day in 4 months, persisting with joint pain, myalgia, rash and malaise. We added tocilizumab treatment 8mg/kg/month, with a good clinical response and significant improvement in acute phase reactants. So far, she has had no adverse events and is under close surveillance due to the history of neoplasia.

Both cases presented had adult onset Still's disease treated with tocilizumab and a very good response to treatment, almost from the first week, improvement in the clinical manifestations of fever, rash and arthropathy, and a frank and rapid reduction in the acute phase reactants (WBC, CRP, ESR). This is similar to the cases reported in the literature that relate very significant improvement of clinical manifestations and acute inflammatory response even in refractory patients with multiple prior therapies. As in the case of our patients, the majority of reports describe that the response is maintained and adverse effects, particularly dyslipidemia, improve with specific treatment.3–11 Although the data available to date are still limited due to the rarity of the disease and limited availability of anti-IL-6 treatment, it seems clear that the use of tocilizumab represents a good alternative for the treatment of this disease, which can be chronic and potentially disabling. Our patients are the first to be reported in Latin American literature.

References
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Adult onset Still's disease: review of 41 cases.
Clin Exp Rheumatol, 29 (2011), pp. 331-336
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Pathogenesis and management of adult-onset Still's disease.
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Treatment of refractory adult-onset Still's disease with tocilizumab: report of two cases and review of the literature.
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Ann Rheum Dis, 70 (2011), pp. 390-392
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R. Suematsu, A. Ohta, E. Matsuura, H. Takahashi, T. Fujii, T. Horiuchi, et al.
Therapeutic response of patients with adult Still's disease to biologic agents: multicenter results in Japan.
Mod Rheumatol, 22 (2012), pp. 712-719

Please cite this article as: Andrade-Ortega L, Irazoque-Palazuelos F, Muñoz-López S, Rosales-Don Pablo VM. Eficacia de tocilizumab en enfermedad de Still del adulto refractaria; a propósito de 2 casos. Reumatol Clin. 2014;10:199–200.

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