Infecciones en niños con artritis idiopática juvenil y comparación con niños sanos

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatría. Fecha de Lectura: 31-03-202

Colchicine treatment in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: A multicenter study in Spain

Objective: To evaluate the efficacy of colchicine therapy in pediatric patients with PFAPA syndrome who present with an incomplete response to the standard treatment or with frequent episodes (an interval of less than 14 days between two disease flares). Methods: A multicenter cohort study of children diagnosed with PFAPA syndrome and treated with colchicine was performed in three separate hospitals located in Spain. The patients clinical and laboratory data were reviewed by accessing their medical records. Response to colchicine was evaluated after 12 months of treatment for frequency, duration, and intensity of PFAPA episodes. Results: A total of 13 children were included in our study, 43% of whom were boys. Median age of the colchicine therapy initiation was 6 years (interquartile range (IQR)=3-9.5). Following a 12-month period of colchicine therapy (median dosage of 0.02 mg/kg/day; IQR=0.02-0.03), a significant decrease in the median number of flares (median 8; IQR=7-14 vs 3; IQR=2-4; p=0.005) and the duration of disease episodes (median 4 days; IQR=3.25-5.125 vs 1 day; IQR=1-2; p=0.003) was observed. Furthermore, the highest degree of fever during disease flares was reduced from median 40ºC (IQR=39.5-40) to 38.5ºC (IQR=37.7-38.9) (p=0.002). Conclusion: Colchicine therapy decreased the frequency and intensity of PFAPA. The use of colchicine could be an effective treatment in pediatric patients with PFAPA syndrome who present with frequent or severe relapses

Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases

Background: Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question. Objective: To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group. Methods: Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins. Results: There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination. Conclusions: We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.This work has been partially supported by a grant from Merck & Co (USA) MISP Call, Reference # 60465.S

Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.

Children with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients. A prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model. A total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5-11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1-1.5) in JIA and 1.12 (95%CI 0.9-1.3) in non-JIA participants (p = 0.19). Age We found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate

Clinical characteristics and prognostic factor in juvenile dermatomyositis: data of the Spanish registry

Abstract Background Juvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients. Methods We retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity. Results One hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5–10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22–47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5–34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6–22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications. Conclusions We describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication

Standardized nailfold capillaroscopy in children with rheumatic diseases : a worldwide study

Objectives: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). Material and methods: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. Results: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. Conclusions: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD

Pictavia Aurea

Este volumen, titulado Pictavia aurea, reúne 131 estudios que constituyen una granada muestra de los debates y las presentaciones en torno a la cultura hispánica del Siglo de Oro que entre los días 11 y 15 de julio de 2011 se dieron en la ciudad de Poitiers (Francia) en el marco del IX congreso de la Asociación Internacional “Siglo de Oro”. Auspiciada por la Universidad de Poitiers, a través del Centro de Estudios de la Literatura española de Entre Siglos (siglos xvii-xviii) (CELES XVII-XVIII) y el laboratorio «Formes et Représentations en Linguistique et Littérature» (FoReLL), la convocatoria reunió en la ciudad francesa a 276 participantes y a un centenar de asistentes en la novena edición del Congreso de la Asociación, que celebró entonces la efeméride del 450o aniversario del nacimiento de Luis de Góngora.A Isaías Lerner, maestro de la filología hispánic