Rol de interleuquina-6 en artritis reumatoide: nuevos conceptos: [revisión] / Role of inteleukin-6 in rheumatoid arthritis: new concepts: [review]

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology that involves complex and not completely elucidated mechanisms. In the recent years, the development of targeted therapies has given new insights into the nature of immunologic interactions involved in its pathogenesis. Until recently, the RA was thought to be predominantly a Th1 disease. New evidence established the preponderant role of the Th17 axis, of which IL-17 and IL-23 are major components. IL-6 has an important role in the differentiation of the Th17 and T regulatory (Treg) lymphocytes. Herein, we review current evidence regarding the role of cytokines in the pathogenesis of RA, especially in the differentiation of Th17 and Treg systems, as well as the deleterious effects of IL-6 and the molecular and clinical consequences of its blockade.

Reunión clínica inter-hospitales: hipertensión arterial y microangiopatía trombótica en lupus eritematoso sistémico / Inter-hospital clinical meeting: hypertension and thrombotic microangiopathy in systemic lupus erythematosus

Se presenta una paciente portadora de lupus eritematoso sistémico (LES), descompensado por múltiples factores, que desarrolló una nefropatía lúpica e hipertensión arterial severa de difícil manejo, asociadas a disfunción orgánica múltiple y microangiopatía trombótica, tratadas con plasmaféresis e inmunosupresión. Se exponen las causas y mecanismos fisiopatológicos más importantes de la hipertensión arterial (HTA) severa en pacientes con LES. Enseguida se analizará específicamente el púrpura trombocitopénico trombótico como causa y/o efecto de HTA en LES.

We present a patient with systemic lupus erythematosus (SLE), outweighed by multiple factors, who developed lupus nephritis and severe hypertension difficult to handle, associated with organ dysfunction and thrombotic microangiopathy treated with plasmapheresis and immunosuppression. This document explains the causes and pathophysiological mechanisms leading to hypertension (HT) in patients with severe SLE. Then specifically analyzed as thrombotic thrombocytopenic purpura cause and / or effect of hypertension in SLE.

Reunión clínica inter-hospitales: síndrome antifosfolípidos catastrófico, un cuadro de microangiopatía / Catastrophic antiphospholipid syndrome, a case of microangiopathy

Se presenta el caso de una mujer joven, sin antecedentes de importancia, que muestra trombosis de grandes y pequeños vasos. A pesar del tratamiento con anticoagulación y corticoides en dosis altas, desarrolla necrosis cutánea y una importante respuesta inflamatoria sistémica con disfunción orgánica múltiple, por lo que .se le indicó plasmaféresis y, posteriormente, rituximab, con buena respuesta. Se discute el síndrome antifosfolípidos con énfasis en los anticuerpos antiprotrombina y la patogenia de la microangiopatía en el síndrome antifosfolípidos catastróficos.

We present the case of a young, otherwise healthy woman, who developed thrombosis of large and small vessels and capillaries. Despite anticoagulation treatment and high doses of glucocorticoids, she developed cutaneous necrosis and systemic inflammatory response with multiple organ dysfunction. Plasmapheresis and rituximab were administered with good response. We discuss the antiphospholipid syndrome, with emphasis on antiprothrombin antibodies and the pathogenesis of microangiopathy in antiphospholipid syndrome.

Papel de los polimorfismos -238 y -308 del promotor del factor de necrosis tumoral alfa en la patogenia y respuesta al tratamiento anti- factor de necrosis tumoral alfa en artritis reumatoide / The influence of -238 and -308 TNF alpha polymorphisms on the pathogenesis and response to treatment in rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects 0.8 percent of the world population, it affects the synovial membrane of joints and the clinical presentation encompasses a wide spectrum, ranging from a mild to a severe and erosive disease that causes joint and cartilage destruction which finally provokes irreversible structural damage and patient disability. In the last years, there have been important advances in the pathogenesis of this disease, the efforts have been concentrated on pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). This protein guides numerous events in the synovial and systemic inflammatory process and is encoded in the Major Histocompability Complex (MHC), one of the most polymorphic of the genome. Polymorphisms affecting the TNFalpha gene and its regulatory regions are associated with RA prevalence and course. There is a possible association between these polymorphisms and the clinical response to the use of monoclonal antibodies anti-TNFalpha. The possibility that the determination of genotypes -238 and -308 may have prognostic and therapeutic consequences is debated nowadays (Rev Méd Chile 2005; 133: 1089-95).

Proteína S libre en embarazadas normales: comparación entre dos métodos / Free protein S (PS) in normal pregnancy: A comparison between two analytical methods

Background: Pregnancy is a physiological hypercoagulable state with an increased incidence of thromboembolic phenomena. There is an increase in the concentrations of most clotting factors, a decrease in concentration of some of the natural anticoagulants and reduced fibrinolytic activity. Changes in PS levels have also been reported. Aim: To establish referral range values of functional PS and free PS antigen, during the second (2nd T) and third trimester (3rd T) of normal gestation. Patients and methods: Forty one normal pregnant women were included in our study, 20 during the 2nd T (22-24 weeks) and 21 during the 3rd T (29-38 weeks). Functional PS was measured by a clot based test and free PS antigen by ELISA. Results: Free PS Antigen was 65.8±18.3% during the 2nd T and 62.3±16.5% during the 3rd T. The figures for normal controls were 106±6.5%. Functional PS was 43.8±13.3 and 25.9±14.6% during the 2nd T and 3rd T, respectively. The figures for normal controls were 97±24% (p <0.001 compared with pregnant women). Free PS antigen did not change from the 2nd to the 3rd T (p=NS), however functional PS fell significantly from the 2nd to the 3rd T (p <0.001) and was significantly lower than free PS antigen in both trimesters (p <0.001). Conclusions: Pregnancy is associated to a decrease in PS. This abnormality is more pronounced for functional PS than free PS antigen and functional PS falls progressively during pregnancy. These assays should not be used to screen for PS deficiency during pregnancy because they could lead to a misdiagnosis.

Uso del rituximab(anticuerpo monoclonal anti-CD20) en lupus eritematoso sistémico refractario a tratamiento: Caso clínico / Rituximab (anti-CD20 monoclonal antibody) for refractory systemic lupus erythematosus: Report of one case

New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m2 for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.

Manifestaciones clínicas de la granulomatosis de Wegener y la poliangeítis microscópica en Santiago-Chile, 1990-2001 / Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients

Background: Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental factors are implicated. Aim: To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. Patients and methods: Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. Results: The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68percent and 57percent respectively).The main clinical features in the MPA group were renal involvement (68percent), peripheral nervous system involvement (57percent), pulmonary hemorrhage (28percent), and skin disease (32percent). In the WG group were alveolar hemorrhage (62percent), renal involvement (78percent), paranasal sinus involvement (57percent), and ocular disease (26percent). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p< 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75percent had pANCA, 4percent had cANCA and 21percent were ANCA negative) and in 55 WG patients (17percent had pANCA, 79percent had cANCA and 4percent were ANCA negative). Global mortality was 18percent and 17percent respectively, and the most common causes of death were infections. Conclusions: The clinical features of our patients are similar to other published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.

Utilidad de determinar el polimorfismo de la región promotora -308 del gen del factor de necrosis tumoral Alfa, en pacientes con artritis reumatoídea / Utility to determine the polymorphism of the promotional region -308 of the gene of the factor of tumorlike necrosis Alpha, in patients with rheumatoid arthritis

La artritis Reumatoídea es una enfermedad inflamatoria sistémica, crónica, de curso habitualmente progresivo, en cuya etiología interactúan mecanismos ambientales favorecidos por una predisposición genética. Existe un amplio espectro de citoquinas involucradas en la patogenia. Entre ellas, el Factor de Necrosis Tumoral Alfa (TNFa) juega un rol protagónico. Esto se ha visto confirmado en el último tiempo con las nuevas terapias biológicas que bloquean la acción de esta citoquina, logrando respuestas de gran impacto en la calidad de vida de los pacientes. En el presente artículo se revisan los elementos que ayudan a entender la fisiopatología, mecanismos reguladores y la importancia de determinar el polimorfismo del promotor del gen del TNF a-308, basados en la experiencia de un grupo de investigación nacional.

Neumonía por varicela en adultos / Varicella pneumonia in adults

La neumonía por varicela es una rara complicación en el curso de una Varicela (10-20 por ciento) de ocurrencia preferentemente en adultos e inmunocomprometidos, potencialmente mortal, de curso variable y parcialmente prevenible. La neumonía por varicela se presenta en los primeros días del cuadro clínico, puede ser asintomática o generar falla respiratoria y requerir asistencia ventilatoria. Su diagnóstico es clínico y por imágenes; los estudios serológicos (medición de IgM) y de aislamiento viral son complementarios. Pese a la posibilidad de efectuar profilaxis en los huéspedes susceptibles con gamaglobulina o aciclovir, la medida más costoefectiva es la vacunación, disponible en Chile. Una vez desencadenado el cuadro, las medidas terapéuticas son restringidas, consistente en aciclovir o valaciclovir usados precozmente y medidas de soportes ventilatorio de ser necesario. Pese a la falta de evidencias sólidas respecto al uso de corticoides, su beneficio parece superar el riesgo involucrado en su uso