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      Dos casos de reactivación de tuberculosis pulmonar por infliximab: Problemas y propuestas de solución Translated title: Two cases of pulmonary tuberculosis reactivation by infliximab: Problems and proposals

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          Abstract

          Introducción: Se han descrito múltiples factores de riesgo para el desarrollo de la tuberculosis; uno recientemente conocido es la inmunosupresión secundaria al uso de infliximab, anticuerpo monoclonal quimérico antifactor de necrosis tumoral-α usado en enfermos con artritis reumatoide o espondilitis anquilosante refractarias a tratamiento y en enfermedad de Crohn fistulizante, entre otros, en los que se ha comunicado reactivación tuberculosa en Estados Unidos y Europa. Presentación de casos: En México sólo se conoce un caso. Presentamos dos más en enfermos con espondiloartropatías HLA-B27 refractarios a tratamiento modificador de la enfermedad. Uno en una mujer de 23 años, después de la segunda dosis de infliximab; otro en un hombre de 32 años, después de la quinta dosis, a la semana 22 de tratamiento. Ambos presentaron forma neumónica cavitada con buena respuesta al tratamiento antituberculoso acortado convencional y suspensión del infliximab. Discusión: La revisión bibliográfica incluye el impacto de los problemas: infliximab-reactivación tuberculosa y la epidemiología tuberculosa actual, medidas preventivas, controversias en detección, tratamiento y fisiopatología de la relación infliximab-reactivación tuberculosa para proponer medidas para su diagnóstico, vigilancia y manejo de nuevos casos aplicables en nuestro entorno

          Translated abstract

          Introduction: There are numerous risk factors for the development of tuberculosis (TB); one recently known is immunosupression produced by infliximab, a chimeric anti-tumor necrosis factor alpha monoclonal antibody used, amongst others, in rheumatoid arthritis, ankylosing spondylitis and Crohn's disease; several cases of reactivation of pulmonary TB have been reported in the United States of America and Europe. Cases presentation: Only one case of reactivation of pulmonary TB has been reported in Mexico. We now present two more cases in patients with HLA-B27 spondyloarthropathy refractory to usual drug management; one occurred in a 23 year old woman after the second dose of infliximab; the other in a 32 year old male, after the fifth dose during the fifth month of treatment. Both developed a cavitating pneumonia, with complete resolution after standard outpatient TB chemotherapy and discontinuation of infliximab. Discussion: The bibliographic review includes the relationship between infliximab and reactivation of pulmonary TB, epidemiology of tuberculosis in Mexico, preventive measures, controversies in the detection, physiopathology and treatment suggestions for the early diagnosis and management in our socioeconomic environment

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          Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group.

          Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.
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            An endotoxin-induced serum factor that causes necrosis of tumors.

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              Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis.

              To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS). Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.
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                Author and article information

                Journal
                iner
                Revista del Instituto Nacional de Enfermedades Respiratorias
                Rev. Inst. Nal. Enf. Resp. Mex.
                Instituto Nacional de Enfermedades Respiratorias (México, DF, Mexico )
                0187-7585
                March 2005
                : 18
                : 1
                : 27-37
                Affiliations
                [01] Sinaloa Culiacán orgnameInstituto Mexicano del Seguro Social orgdiv1Hospital General Regional No. 7 México
                Article
                S0187-75852005000100006 S0187-7585(05)01800100006
                91ac9f8d-2120-4715-915e-b6f64c6b2303

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 13 January 2005
                : 10 November 2004
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 50, Pages: 11
                Product

                SciELO Mexico

                Categories
                Trabajos originales

                TNF-α,reactivación tuberculosa,pulmonary tuberculosis,Infliximab,reactivation

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