RESUMEN
Systemic-onset juvenile idiopathic arthritis (SoJIA) accounts for a relatively small proportion of patients with juvenile arthritis. Its clinical manifestations are unique among the subsets of JIA and studies of cytokine profiles suggest differences between the underlying mechanisms of the different diseases. SoJIA may, in fact, be better classified separately from other subtypes of JIA. New biologic agents that are currently licensed or being tested, target the cytokines interleukin-1 and interleukin-6 and appear to be effective in treating SoJIA. By contrast, anti-tumor necrosis factor therapy is much less, if at all, successful in this subgroup of JIA. This article reviews the current literature on the pathogenesis and treatment of SoJIA.
Asunto(s)
Artritis Juvenil/complicaciones , Síndrome de Klinefelter/complicaciones , Adolescente , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/fisiopatología , Humanos , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/fisiopatología , Masculino , Metotrexato/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To document and evaluate the scores that normal, healthy children achieve when performing 9 maneuvers of the Childhood Myositis Assessment Scale (CMAS). METHODS: A total of 303 healthy children, 4-9 years of age, were scored as they performed 9 CMAS maneuvers. The data were then evaluated to determine whether normal scores for some maneuvers are age and sex dependent. RESULTS: All children were able to achieve maximum possible scores for the supine to prone, supine to sit, floor sit, floor rise, and chair rise maneuvers. All but 2 4-year-olds achieved a maximum possible score for the arm raise/duration maneuver. Performance of the head lift and sit-up maneuvers varied significantly, depending primarily on age. Children in all age groups had less difficulty performing the leg lift than the head lift or sit-up. CONCLUSION: The normative data generated by this study are of value for interpreting the serial CMAS scores of children with idiopathic inflammatory myopathies.
Asunto(s)
Evaluación de la Discapacidad , Músculo Esquelético/fisiología , Miositis/diagnóstico , Índice de Severidad de la Enfermedad , Niño , Preescolar , Femenino , Cabeza/fisiología , Humanos , Pierna/fisiología , Masculino , Movimiento , Miositis/fisiopatología , Curva ROC , Valores de ReferenciaRESUMEN
OBJECTIVE: To examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores. METHODS: One hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated. RESULTS: The intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30. CONCLUSION: The CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM.
Asunto(s)
Miositis/diagnóstico , Índice de Severidad de la Enfermedad , Adolescente , Niño , Preescolar , Evaluación de la Discapacidad , Humanos , Actividad Motora , Miositis/fisiopatología , Variaciones Dependientes del Observador , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
Infection with gastrointestinal nematodes exerts profound effects on both the immune and physiological responses of the host. We showed previously that the Th2 cytokines, IL-4 and IL-13, induce STAT6-dependent changes in intestinal epithelial cell permeability, absorption, and secretion that are similar to those observed in a secondary infection with Heligmosomoides polygyrus. In the current study we investigated whether nematode-induced effects on epithelial cell function were 1) generic, 2) dependent upon STAT6, and 3) attributable to direct effects on the epithelial cells themselves or mediated by effects on enteric nerves. Our results demonstrate that infection of BALB/c mice with three different gastrointestinal nematodes (H. polygyrus, Nippostrongylus brasiliensis, and Trichinella spiralis) alters intestinal epithelial cell function by decreasing resistance, glucose absorption, and secretory responses to 5-hydroxytryptamine and acetylcholine, two critical mediators in the submucosal reflex pathway. These modified responses are dependent on STAT6 and are the result of both direct effects and indirect effects mediated through enteric nerves.
Asunto(s)
Permeabilidad de la Membrana Celular/fisiología , Parasitosis Intestinales/patología , Parasitosis Intestinales/fisiopatología , Mucosa Intestinal/metabolismo , Infecciones por Nematodos/patología , Infecciones por Nematodos/fisiopatología , Transactivadores/fisiología , Animales , Femenino , Glucosa/antagonistas & inhibidores , Glucosa/metabolismo , Absorción Intestinal/genética , Absorción Intestinal/inmunología , Parasitosis Intestinales/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/inervación , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Infecciones por Nematodos/inmunología , Nematospiroides dubius/inmunología , Nippostrongylus/inmunología , Factor de Transcripción STAT6 , Sodio/metabolismo , Tetrodotoxina/farmacología , Transactivadores/deficiencia , Transactivadores/genética , Trichinella spiralis/inmunologíaRESUMEN
Gastrointestinal nematode infections generally invoke a type 2 cytokine response, characterized by the production of IL-4, IL-5, IL-9, and IL-13. Among these cytokines, IL-4 and IL-13 exhibit a functional overlap that can be explained by the sharing of a common receptor or receptor component (IL-4Ralpha). Binding of IL-4 by either the type 1 or 2 IL-4R, or of IL-13 by the type 2 IL-4R, initiates Jak-dependent tyrosine phosphorylation of the IL-4Ralpha-chain and the transcription factor, STAT6. In the present study, we investigated: 1) whether IL-13 has effects on intestinal epithelial cells similar to those observed with IL-4, and 2) whether the effects of IL-4 and IL-13 depend on STAT6 signaling and/or mast cells. BALB/c, STAT6(-/-), and mast cell-deficient W/W(v) mice or their +/+ littermates were treated with a long-lasting formulation of recombinant mouse IL-4 (IL-4C) or with IL-13 for seven days. Segments of jejunum were mounted in Ussing chambers to measure mucosal permeability; chloride secretion in response to PGE(2), histamine, 5-hydroxytryptamine, or acetylcholine; and Na(+)-linked glucose absorption. IL-4C and IL-13 increased mucosal permeability, decreased glucose absorption, and decreased chloride secretion in response to 5-hydroxytryptamine. These effects were dependent on STAT6 signaling. Responses to PGE(2) and histamine, which were dependent on mast cells and STAT6, were enhanced by IL-4C, but not by IL-13. The effects of IL-4 and IL-13 on intestinal epithelial cell function may play a critical role in host protection against gastrointestinal nematodes.