Transición en niños y adolescentes con enfermedades reumáticas

El objetivo general de esta investigación es poner de manifiesto los problemas durante el proceso de transición de adolescentes y jóvenes con enfermedades reumáticas y sugerir indicaciones para llevarla a cabo. Proporcionar una atención dirigida durante la adolescencia y asegurar la continuidad de su asistencia en las unidades de reumatología es fundamental para que sean capaces de conseguir un funcionamiento óptimo en la vida adulta. Para ello, se realizó una evaluación de la situación actual de la transición en adolescentes y jóvenes con enfermedades reumáticas mediante una encuesta a reumatólogos pediátricos europeos con preguntas dirigidas acerca de su práctica real y una descripción de los programas de transición en reumatología mediante una revisión sistemática. De este modo, se identificaron las estrategias y herramientas más relevantes para el desarrollo de los programas y se elaboraron una serie de recomendaciones mediante un proceso de consenso para mejorar la asistencia durante el proceso de transición. Los programas de transición de mayor calidad contienen seis puntos críticos: un programa de transición estructurado y por escrito; una planificación individualizada del proceso, con flexibilidad en su implementación y duración; un comienzo precoz; un coordinador que asuma la responsabilidad de la transición; la promoción de conocimientos y habilidades a jóvenes y sus padres; y la transmisión de la información relevante y traslado a la unidad de adultos. Sin embargo, faltan indicadores estandarizados y medidas que permitan evaluar adecuadamente el proceso de la transición en jóvenes con enfermedades reumáticas. Los resultados de nuestra encuesta demuestran limitaciones en la implantación real de la transición y una escasa disponibilidad de recursos. Aunque se considera necesario proporcionar una atención específica en la transición a la atención en las unidades de adultos, no todos los centros desarrollan un programa de transición y es más frecuente un proceso de transición informal que la aplicación de programas estructurados. La variabilidad encontrada depende de factores locales como los sistemas de atención sanitaria, marcos regulatorios y la disponibilidad de financiación. Por último, se elaboran 12 recomendaciones que proporcionan información relevante sobre las estrategias necesarias para alcanzar resultados óptimos en la transición de jóvenes con enfermedades reumáticas, según la evidencia disponible y la opinión de un grupo multidisciplinar de expertos. Dado el gran interés de los reumatólogos pediátricos y de adultos por mejorar el proceso de transición, se espera que estas recomendaciones sean útiles para cambiar la práctica actual

Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients.Funding for open access charge: Universidad de Málaga/CBU

Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group

Background: Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. Objective: This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. Methods: Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). Results: A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p 900,000 cells/mm3, maximum temperature 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. Conclusions: In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary

TLR7 gain-of-function genetic variation causes human lupus

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA and binds to guanosine. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2',3'-cGMP1 and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition

Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group

KAWA-RACE study group.[Background] Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children.[Objective] This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain.[Methods] Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals).[Results] A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p 900,000 cells/mm3, maximum temperature 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms.[Conclusions] In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary.CC received a grant from Spanish Society of Paediatric Rheumatology (SERPE), 2015.Peer reviewe