Clinical characteristics and diagnostic indicators of macrophage activation syndrome in patients with systemic lupus erythematosus and adult-onset Still's disease / 北京大学学报(医学版)

OBJECTIVE@#To analyze and compare the clinical and laboratory characteristics of macrophage activation syndrome (MAS) in patients with systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD), and to evaluate the applicability of the 2016 European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organization classification criteria for MAS complicating systemic juvenile idiopathic arthritis (sJIA) in different auto-immune diseases contexts and to propose new diagnostic predictive indicators.@*METHODS@#A retrospective analysis was conducted on the clinical and laboratory data of 24 SLE patients with MAS (SLE-MAS) and 24 AOSD patients with MAS (AOSD-MAS) who were hospitalized at Peking University People's Hospital between 2000 and 2018. Age- and sex-matched SLE (50 patients) and AOSD (50 patients) diagnosed in the same period without MAS episodes were selected as controls. The cutoff values for laboratory indicators predicting SLE-MAS and AOSD-MAS were determined using receiver operating characteristic (ROC) curves. Furthermore, the laboratory diagnostic predictive values for AOSD-MAS were used to improve the classification criteria for systemic juvenile idiopathic arthritis-associated MAS (sJIA-MAS), and the applicability of the revised criteria for AOSD-MAS was explored.@*RESULTS@#Approximately 60% of SLE-MAS and 40% of AOSD-MAS occurred within three months after the diagnosis of the underlying diseases. The most frequent clinical feature was fever. In addition to the indicators mentioned in the diagnosis criteria for hemophagocytic syndrome revised by the International Society for Stem Cell Research, the MAS patients also exhibited significantly elevated levels of aspartate aminotransferase and lactate dehydrogenase, along with a significant decrease in albumin. Hemophagocytosis was observed in only about half of the MAS patients. ROC curve analysis demonstrated that the optimal discriminative values for diagnosing MAS was achieved when SLE patients had ferritin level≥1 010 μg/L and lactate dehydroge-nase levels≥359 U/L, while AOSD patients had fibrinogen levels≤225.5 mg/dL and triglyceride levels≥2.0 mmol/L. Applying the 2016 sJIA-MAS classification criteria to AOSD-MAS yielded a diagnostic sensitivity of 100% and specificity of 62%. By replacing the less specific markers ferritin and fibrinogen in the 2016 sJIA-MAS classification criteria with new cutoff values, the revised criteria for classifying AOSD-MAS had a notable increased specificity of 86%.@*CONCLUSION@#Secondary MAS commonly occurs in the early stages following the diagnosis of SLE and AOSD. There are notable variations in laboratory indicators among different underlying diseases, which may lead to misdiagnosis or missed diagnosis when using uniform classification criteria for MAS. The 2016 sJIA-MAS classification criteria exhibit high sensitivity but low specificity in diagnosing AOSD-MAS. Modification of the criteria can enhance its specificity.

A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis / 中国当代儿科杂志

OBJECTIVES@#To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA.@*METHODS@#In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14+ mononuclear cells, CD4+ T lymphocytes, and CD8+ T lymphocytes.@*RESULTS@#The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4+ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8+ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14+ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05).@*CONCLUSIONS@#The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA.@*METHODS@#Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA.@*RESULTS@#The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64.@*CONCLUSIONS@#The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

Optic neuromyelitis in relation with juvenile idiopathic arthritis: A case report

Optic neuromyelitis (ONM), also called neuromyelitis optica spectrum (Neuromyelitis Optica Spectrum Disorders, NMOSD) is recognized as an inflammatory autoimmune demyelinating disease of the central nervous system, mediated by autoantibodies against the aquaporin-4 receptor (AQP4-IgG). It predominantly affects the optic nerves and the spinal cord.1-3 It is known that patients with immune disorders are more likely to present other autoimmune diseases, but the relation between juvenile idiopathic arthritis and ONM has not been completely described.5 In this paper, we report a case of a patient with juvenile idiopathic arthritis, presenting with a rapidly progressive neurological condition, who is treated with biological drugs.1-4

La neuromielitis óptica (NMO), también llamada espectro de la neuromielitis óptica (neuromyelitis optica spectrum disorders) se reconoce como una enfermedad inflamatoria, autoinmune, desmielinizante del sistema nervioso central, mediada por autoanticuerpos contra el receptor de acuaporina 4 (AQP4-IgG) que afecta predominantemente a los nervios ópticos y la médula espinal1-3. Es conocido que los pacientes con trastornos inmunitarios tienen más probabilidades de presentar otras enfermedades autoinmunes; sin embargo, no está completamente descrita la asociación entre artritis idiopática juvenil y NMO5. En este escrito se reporta el caso de una paciente que cursa con artritis idiopática juvenil, inició con compromiso neurológico rápidamente progresivo, y es tratada con medicamentos biológicos1-4.

Enfermedad de Scheuermann lumbar atípica en rara asociación con artritis idiopática juvenil / Atypical lumbar Scheuermann disease and juvenile idiopathic arthritis: a rarely association

El dolor lumbar en los adolescentes es causa frecuente de motivo de consulta en reumatología y obedece a diferentes causas. Se presenta un caso clínico de un adolescente de 14 años de edad, de procedencia rural que acudió a consulta refiriendo dolor y aumento de volumen de ambas rodillas de 3 meses de evolución, acompañado de dolor lumbar desde hacía más de 2 años y que había requerido tratamiento con antinflamatorios no esteroideos y reposo, sin otros síntomas sistémicos acompañantes. Al examen físico se encontró artritis de rodillas, aumento de la cifosis fisiológica en la columna dorsal y puntos sacroilíacos positivos. En los exámenes complementarios fue significativa la presencia del HLA-B27, sinovitis en bolsa subcuadricipital bilateral detectada mediante ultrasonido de rodillas, así como hallazgos en las radiografías a nivel de los cuerpos de las vértebras lumbares característicos de la enfermedad de Scheuermann, y esclerosis de ambas sacroilíacas, características de artritis idiopática juvenil. Se concluyó que el paciente padecía de dos afecciones que por mecanismos diferentes causan dolor lumbar(AU)

Low back pain in adolescents is a frequent reason for consultation in rheumatology and is due to different causes. A clinical case of a 14-year-old adolescent from rural origin who comes to the clinic reporting pain and volume increase in both knees of three months of evolution accompanied by low back pain of more than two years of evolution that had required treatment is presented. with non-steroidal anti-inflammatory drugs and rest, without other accompanying systemic symptoms, physical examination revealed knee arthritis, increased physiological kyphosis in the thoracic spine and positive sacroiliac points. In the complementary tests, the presence of HLA-B27, synovitis in the bilateral sub quadriceps bursa on ultrasound of the knees, findings in the radiographs at the level of the bodies of the lumbar vertebrae characteristic of Scheuermann's disease, and sclerosis of both sacroiliacs' characteristic of juvenile idiopathic arthritis, it is concluded that the patient suffers from two conditions, which by different mechanisms cause low back pain(AU)

Afectación articular en adolescente con artritis idiopática juvenil / Joint involvement in an adolescent with juvenile idiopathic arthritis

La artritis idiopática juvenil es una enfermedad inflamatoria sistémica y crónica que se caracteriza por el daño articular y la presencia de manifestaciones extraarticulares que afectan distintos órganos y sistemas de órganos del cuerpo humano. Como enfermedad tiene varias formas clínicas de presentación que se corresponden con posibles enfermedades en la edad adulta. El objetivo de la presente investigación es presentar el caso de un adolescente de 14 años de edad con historia de cuadro inflamatorio poliarticular de más de 3 años de duración con deformidad articular en ambas rodillas, lo cual es poco frecuente y que es expresión del proceso inflamatorio mantenido. Después del tratamiento fue dado de alta con una mejoría notable de los rangos de movimiento articular. En la actualidad evoluciona satisfactoriamente y lleva alrededor de un año en seguimiento en consulta externa sin exacerbaciones de la actividad clínica de la enfermedad. Se considera importante el reporte del caso para concientizar a la comunidad médica en relación con el diagnóstico precoz de esta enfermedad para minimizar el riesgo de aparición de complicaciones articulares y sistémicas(AU)

Juvenile idiopathic arthritis is a systemic and chronic inflammatory disease characterized by joint involvement and the presence of extra-articular manifestations that occur in different organs and organ systems of the human body. As a disease, it includes a series of clinical forms of presentation that correspond to possible diseases in adulthood. The objective of this research is to present the case of a 14-year-old adolescent with a history of polyarticular inflammatory symptoms lasting more than three years with the presence of rare joint deformity in both knees, which is an expression of the sustained inflammatory process. The case report is considered important to raise awareness in the medical community regarding the early diagnosis of this disease to minimize the risk of the appearance of joint and systemic complications(AU)

Juvenile otosclerosis: radio-clinical features and outcomes of surgical treatment

Purpose: To review the radio-clinical features and to evaluate the outcomes of surgery approaches for the treatment of otosclerosis in pediatric population. Methods: It's a retrospective study including 12 patients under 18 years of age, diagnosed with otosclerosis and using data over a 24 ­ year ­period (1996-2020). A clinical examination, an audiometric assessment and a computed tomography of the temporal bone (CT-Scan) prior to surgery had been performed in all cases. All patients underwent surgical treatment under general anesthesia. Follow ­up was essentially clinical and audiometric with a mean period of 4years. Results: Mean age of our patients was 15.3 with a ratio of 0.5. Only three of them had a family history of otosclerosis. Major functional sign was hearing loss; tinnitus was noted in only 5 cases. CT-Scan had shown typical radiographic evidence of otosclerosis grade Ia (Veillon classification) in 9 cases, grade Ib in 1 case and no abnormalities in 2 cases. Surgery was performed in all cases: 8 patients underwent stapedotomy and 4 had stapedectomy. The audiometric results were good, air-bone gap closure to within 10 dB was achieved in 84% of cases (10 cases) and to within 20dB in 100% of cases at last follow-up. Conclusion: Audiometric and radiological assessments are essential to guide the diagnosis and the treatment of juvenile otosclerosis. Stapes surgery is a good option for closing the air-bone gap in children with bilateral juvenile otosclerosis

Studying Juvenile Idiopathic Arthritis through a Network Medicine Approach / Estudando a Artrite Idiopática Juvenil mediante uma abordagem de medicina de redes

Juvenile Idiopathic Arthritis (JIA) is a group of inflammatory conditions of unknown etiology whose underlying molecular pathophysiology is still not well characterized. Several studies have attempted to fill this gap by characterizing the gene expression profiles of JIA patients. However, there is a lack of systematic assessment of the reliability of these transcriptome results on the disease classification, prescription, and monitoring. In addition, despite this disease is more common in females, none of these studies have tried to assess the impact of sex on disease pathophysiology. In this project, we performed a comprehensive systematic review and a gene expression meta-analysis to reveal the core molecular JIA pathophysiology taking into consideration the patient sex. We gathered and cataloged more than 60,000 entries of genomic features reported as JIA-related in the functional genomics literature, and found a dramatic disparity among the JIA transcriptome studies. Near 15,000 genes have been reported as perturbed in JIA leukocytes. Less than one percent of these genes were reported in at least a quarter of the reviewed studies. We then removed the study-specific analytical bias by re-analyzing more than 700 unique pediatric transcriptome profiles from nine JIA studies using a common analytical framework. The differential expression results from different studies were combined using a random effect model meta-analysis approach. We implemented this differential gene expression meta-analysis methodology in the MetaVolcanoR R package that we made available in Bioconductor. Using this package, we confirmed several gene expression signatures previously associated with JIA and uncover new genes whose expression was perturbed in JIA patients. The effect sizes of the topmost reported perturbed genes coincide with our meta-analysis results. Through a meta-coexpression approach, we characterized the cell type signatures of circulating leukocytes in the JIA affected children. Additionally, we characterized the JIA sexual dimorphism. We found that systemic JIA female patients over-activate a gene expression signature which comprises early myelocytes and band neutrophil expression markers. This signature is correlated with the disease status and response to IL-1 receptor blockade. This suggests that sJIA pathophysiology is characterized by a sexually dimorphic neutrophilia that impacts disease progression and the response to anti-IL-1 treatments. We further assessed this immature neutrophil and female-biased signature in other contexts. We found that this signature presents a sex-dependent expression over human lifetime, in other inflammatory diseases, and its expression increases during pregnancy

A Artrite Idiopática Juvenil (AIJ) é um grupo de condições inflamatórias de etiologia desconhecida, cuja patofisiologia molecular subjacente ainda não está bem caracterizada. Vários estudos tentaram preencher essa lacuna, caracterizando os perfis de expressão gênica de pacientes com AIJ. No entanto, há uma falta de avaliação sistemática desses resultados transcriptômicos na classificação, prescrição e monitoramento da doença. Além disso, apesar de esta doença ser mais comum em mulheres, nenhum desses estudos tentou avaliar o impacto do sexo na fisiopatologia da doença. Neste projeto, realizamos uma revisão sistemática abrangente e uma metanálise de expressão gênica para revelar a fisiopatologia molecular da AIJ levando em consideração o sexo do paciente. Reunimos e catalogamos mais de 60.000 entradas de características genômicas reportadas como relacionadas à AIJ na literatura. Entre os estudos de transcriptoma, encontramos uma disparidade dramática. Cerca de 15.000 genes foram reportados como perturbados nos leucócitos da AIJ, sendo que menos de um por cento desses genes foram relatados em pelo menos um quarto dos estudos revisados. Em seguida, re-analisamos mais de 700 transcriptomas pediátricos de nove estudos usando uma abordagem analítica comum. Os resultados de expressão diferencial foram combinados usando meta-análise de modelo de efeitos aleatórios. Implementamos esta abordagem de meta-análise de expressão gênica diferencial no pacote MetaVolcanoR R que disponibilizamos no Bioconductor. Usando este pacote, confirmamos várias assinaturas de expressão gênica previamente associadas à AIJ e descobrimos novos genes cuja expressão está perturbada em pacientes com AIJ. Os tamanhos dos efeitos dos genes mais reportados como perturbados coincidem com os resultados da nossa meta-análise. Por meio de uma análise de meta-co-expressão, caracterizamos as assinaturas dos tipos de leucócitos circulantes. Além disso, caracterizamos o dimorfismo sexual da AIJ. Descobrimos que pacientes do sexo feminino com AIJ sistêmica super-ativam genes característicos de mielócitos precoces e neutrófilos bastonetes. Esta assinatura está correlacionada com o estado clínico da doença e à resposta ao tratamento por bloqueio do receptor de IL-1. Isto sugere que a fisiopatologia da AIJs é caracterizada por uma neutrofilia sexualmente dimórfica que afeta a progressão da doença e a resposta aos tratamentos anti-IL-1. Avaliamos ainda esta assinatura neutrofílica em outros contextos. Descobrimos que essa assinatura apresenta uma expressão dependente do sexo ao longo da vida humana, em outras doenças inflamatórias, e sua expressão aumenta durante a gravidez

Tuberculosis miliar en pacientes en tratamiento con adalimumab, una asociación no tan frecuente en pediatría / Miliary tuberculosis in patients treated with adalimumab, an association not so frequent in pediatrics

Los antagonistas del Factor de Necrosis Tumoral-α, son medicamentos que en los últimos años han tenido un incremento de su uso en pacientes con condiciones inflamatorias inmunomediadas en pediatría, como la Artritis Idiopática Juvenil y la Enfermedad Inflamatoria Intestinal. El uso de estos medicamentos en adultos tiene una fuerte asociación con la primoinfección o reactivación por Mycobacterium tuberculosis, pero en niños la evidencia es limitada. Se presentan 2 casos de pacientes tratados con adalimumab, quienes, a pesar de un buen control de su enfermedad y una prueba de tuberculina negativa al inicio de la terapia, desarrollaron tuberculosis miliar en el seguimiento, con importantes implicaciones para su salud. El tamizaje de tuberculosis latente con tuberculina/IGRAS (Interferón-γ release assays, por sus siglas en inglés) y un alto índice de sospecha de tuberculosis, son las herramientas disponibles para una adecuada identificación de la tuberculosis en pacientes que reciben crónicamente estas terapias.

Tumor Necrosis Factor-α antagonists are drugs that in recent years have seen an increase in their use in patients with immune-mediated inflammatory conditions in pediatrics such as Juvenile Idiopathic Arthritis and Inflammatory Bowel Disease. The use of these drugs in adults has a strong association with primary infection or reactivation by mycobacterium tuberculosis, but in children the evidence is limited. We present 2 cases of patients treated with adalimumab who, despite good control of their disease and a negative tuberculin test at the beginning of therapy, developed miliary tuberculosis during follow-up with important implications for their health. Screening for latent tuberculosis with tuberculin / IGRAS (Interferón-γ release assays) and a high index of suspicion for tuberculosis are the tools available for an adequate identification of tuberculosis in patients who receive these therapies chronically.

Juvenile otosclerosis: radio-clinical features and outcomes of surgical treatment

Purpose: To review the radio-clinical features and to evaluate the outcomes of surgery approaches for the treatment of otosclerosis in pediatric population. Methods: It's a retrospective study including 12 patients under 18 years of age, diagnosed with otosclerosis and using data over a 24 ­ year ­period (1996-2020). A clinical examination, an audiometric assessment and a computed tomography of the temporal bone (CT-Scan) prior to surgery had been performed in all cases. All patients underwent surgical treatment under general anesthesia. Follow ­up was essentially clinical and audiometric with a mean period of 4years. Results: Mean age of our patients was 15.3 with a ratio of 0.5. Only three of them had a family history of otosclerosis. Major functional sign was hearing loss; tinnitus was noted in only 5 cases. CT-Scan had shown typical radiographic evidence of otosclerosis grade Ia (Veillon classification) in 9 cases, grade Ib in 1 case and no abnormalities in 2 cases. Surgery was performed in all cases: 8 patients underwent stapedotomy and 4 had stapedectomy. The audiometric results were good, air-bone gap closure to within 10 dB was achieved in 84% of cases (10 cases) and to within 20dB in 100% of cases at last follow-up. Conclusion: Audiometric and radiological assessments are essential to guide the diagnosis and the treatment of juvenile otosclerosis. Stapes surgery is a good option for closing the air-bone gap in children with bilateral juvenile otosclerosis

Clinical analysis of 5 cases of systemic juvenile idiopathic arthritis with coronary artery dilatation / 中华儿科杂志

Objective: To investigate the clinical characteristics of systemic juvenile idiopathic arthritis combined with coronary artery dilatation. Methods: A retrospective analysis was performed on the clinical data, including clinical manifestations, blood routine, inflammatory factors, echocardiography, vascular ultrasound and CT angiography, treatment and outcomes, etc, of 5 cases with systemic juvenile idiopathic arthritis combined with coronary artery dilation admitted to Department of Rheumatology in the affiliated Children's Hospital of Capital Institute of Pediatrics from May 2019 to June 2021. Results: There were 2 males and 3 females among 5 cases. The onset age ranged from 7 months to 4 years 7 months.The diagnostic time ranged from 1.5 months to 3.0 months.Four cases were diagnosed as atypical Kawasaki disease. Three cases showed unilateral coronary artery dilation.Two cases showed bilateral coronary artery dilation.Four cases developed multiple organ injuries.Three cases developed macrophage activation syndrome.Three cases developed lung injury.Two cases developed pericardial effusion.One case developed pulmonary hypertension.As for treatment, 3 cases treated with methylprednisolone pulse therapy and methotrexate combined with cyclosporine, improved after the final application of biological agents, and have stopped prednisone. The other 2 cases were treated with adequate oral prednisone and gradually reduced, and methotrexate was added at the same time, 1 case relapsed in the process of reduction. No other vascular involvement was found in 5 cases. Coronary artery dilation recovered completely after 1 to 3 months of treatment. Conclusions: Systemic juvenile idiopathic arthritis combined with coronary artery dilatation has the clinical characteristics of small onset age, long diagnostic time, prone to multiple organ injuries. Corticosteroids and conventional immunosuppressive agents are not sensitive, and biological agents should be used as soon as possible.The prognosis of coronary artery dilation is good after timely treatment.

Treatment of 11 cases of juvenile idiopathic arthritis by intra-articular injection of adalimumab / 中华儿科杂志

Objective: To evaluate the efficacy and safety of intra-articular injection of adalimumab (ADA) in the treatment of refractory oligoarticular juvenile idiopathic arthritis (JIA). Methods: This was a retrospective study. Clinical data on age, gender, and symptoms of joint swelling and pain were collected from 11 children with refractory oligoarticular JIA involving only knee joints admitted to Department of Rheumatism and Immunology of Children's Hospital, Capital Institute of Pediatrics from November 2019 to October 2020. The physician and parent-child evaluation of disease activity, the number of active joints, and the level of erythrocyte sedimentation rate (ESR) at different treatment time points were analyzed at every 4-week observation point after drug administration, and the non-parametric Kruskal-Wallis test was used to compare the differences in clinical evaluation indicators and changes in laboratory tests at different treatment times. The follow-up period was 6 months. Results: Among the 11 children, 5 were boys and 6 were girls. The age was 3.0 (2.8) years. All 11 children had symptoms of joint swelling and pain as well as limitation of movement. After 3 intra-articular injections of ADA, the joint symptoms of 11 children were better than before treatment; the joint symptoms of 7 children disappeared completely, and no recurrence occurred during the 6-month follow-up period. At different treatment times, physician and parent-child evaluation of disease activity, a gradual decrease in the number of active joints in the children, ESR, and juvenile arthritis disease activity score with 27 joints were all statistically significant (χ2=53.99, 59.37, 32.87, 40.07, 54.00, all P<0.001).No significant adverse drug reactions were observed in any of the 11 children during treatment and follow-up. Conclusion: Intra-articular injection of ADA in the treatment of refractory oligoarticular JIA has a significant effect in controlling joint symptoms and is relatively safe.

Niveles de ferritina en artritis idiopática juvenil de inicio sistémico comparada con otras fiebres de origen desconocido: estudio multicéntrico de pruebas diagnósticas / Ferritin levels in children with juvenile idiopathic arthritis of systemic onset and children with other causes of fever of unknown origin: A multicenter study of diagnostic tests

Resumen | Introducción. No se dispone de pruebas sensibles ni específicas para diagnosticar la artritis idiopática juvenil sistémica. Objetivo. Evaluar la utilidad diagnóstica de niveles de ferritina total cinco veces por encima del valor normal (ferritina total>5N) y el porcentaje disminuido (menor de o igual a 20 % de la ferritina total) de la ferritina glucosilada (ferritina glucosilada<20 %) para el diagnóstico de artritis idiopática juvenil sistémica en pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica. Materiales y métodos. Se hizo un estudio observacional de pruebas diagnósticas de corte transversal en menores de 16 años hospitalizados entre el 2010 y el 2014. El patrón diagnóstico de referencia fue el cumplimiento de los criterios de clasificación o diagnóstico confirmado en el seguimiento. Se determinaron las medidas de utilidad de las pruebas. Resultados. Se incluyeron 40 pacientes con fiebre de origen desconocido: 11 con artritis idiopática juvenil sistémica y 29 con otros diagnósticos. La mediana de la ferritina total fue mayor en la artritis idiopática juvenil sistémica (3.992 ng/ml) comparada con otras causas de fiebre de origen desconocido (155 ng/ml) (p=0,0027), así como la ferritina total>5N (90,91 % Vs. 51,72 %) (p=0,023). El porcentaje de ferritina glucosilada≤20 % fue de 96,5 % en otras fiebres de origen desconocido en comparación con la artritis idiopática juvenil sistémica (81,8 %) (p=0,178). La ferritina total>5N tuvo una sensibilidad del 91 %, una especificidad del 48 %; un cociente de probabilidades (Likelihood Ratio, LR) positivo de 1,76 y uno negativo de 0,19, demostrando mayor utilidad para el diagnóstico que la combinación de la ferritina total>5N y ferritina glucosilada≤20 %, cuya sensibilidad fue del 81,8 %, la especificidad del 48,3 %, un cociente de probabilidades LR positivo de 1,58 y un LR negativo de 0,38. Conclusión. En pacientes con fiebre de origen desconocido evaluados por reumatología pediátrica, la ferritina total>5N demostró ser útil como prueba de tamización para el diagnóstico de artritis idiopática juvenil sistémica.

Abstract | Introduction: There are no sensitive or specific tests available to diagnose systemic juvenile idiopathic arthritis (sJIA). Objective: To assess the utility as diagnostic tests of total ferritin (TF) levels greater than 5 times the normal value (TF>5N) and the decreased percentage (less than or equal to 20% of TF) of glycosylated ferritin (GF≤20%) for the diagnosis of sJIA in patients with fever of unknown origin evaluated by pediatric rheumatology. Materials and methods: We conducted an observational, cross-sectional study of diagnostic tests in children under 16 years of age hospitalized between 2010 and 2014. The reference diagnostic standard was the fulfillment of the classification criteria or confirmed diagnosis at follow-up. We determined the measures of utility of the tests. Results: We included 40 patients with fever of unknown origin, 11 with sJIA, and 29 with other diagnoses. The median TF was higher in sAIJ (3992 ng/ml) versus other causes of fever of unknown origin (155 ng/ml) (p=0.0027), as well as TF>5N (90.91% versus 51.72%) (p=0.023). The percentage of GF≤20% was higher in patients with other causes of fever of unknown origin (96.5%) compared to sJIA (81.8%) (p=0.178). TF>5N had a sensitivity of 91%, specificity of 48%, positive likelihood ratio (LR) of 1.76, and negative LR of 0.19 demonstrating greater utility for the diagnosis of sJIA than the combination of FT> 5N with GFR <20%, with a sensitivity of 81.8%, specificity of 48.3%, positive LR of 1.58, and negative LR of 0.38. Conclusion: In patients with FUO evaluated by pediatric rheumatology, TF> 5N proved useful as a screening test for the diagnosis of sJIA.

Uveítis asociada a la artritis idiopática juvenil / Uveitis associated to juvenile idiopathic arthritis

Objetivo: Caracterizar las uveítis asociadas a la artritis idiopática juvenil. Métodos: Se realizó un estudio observacional, descriptivo, de corte transversal, donde se evaluaron las variables edad, raza, sexo, lateralidad de la uveítis, clasificación anatómica, agudeza visual mejor corregida, presencia de complicaciones y tratamiento. Resultados: Predominaron los mayores de seis años, el sexo femenino y la raza blanca. En cuanto a la lateralidad hubo mayor predominio de las bilaterales, con localización anatómica anterior. En los resultados visuales sobresalieron los que presentaban una agudeza visual mejor corregida ≥ 0,5. Las complicaciones más frecuentes fueron: la pérdida visual, la hipertensión ocular y la queratopatía en banda. Con respecto al tratamiento, la mayoría de los pacientes tenían asociado metotrexate al tratamiento tópico y oral con esteroides. Conclusión: La uveítis asociada a la artritis idiopática juvenil sigue siendo un problema importante de salud en la infancia a pesar de los avances en los programas de atención a esta enfermedad; por tanto, el diagnóstico precoz, el seguimiento estricto y el tratamiento adecuado son los pilares para una mejor evolución(AU)

Objective: Characterize uveitis associated to juvenile idiopathic arthritis. Methods: A cross-sectional observational descriptive study was conducted based on evaluation of the following variables: age, race, sex, laterality of uveitis, anatomical classification, best corrected visual acuity, presence of complications and treatment. Results: A predominance was observed of patients aged over six years, female sex and white race. Bilateral uveitis prevailed, with anterior anatomical location. Patients with a best corrected visual acuity ≥ 0.5 stood out for their visual results. The most common complications were visual loss, ocular hypertension and band keratopathy. Most patients had methotrexate associated to topical and oral treatment with steroids. Conclusion: Uveitis associated to juvenile idiopathic arthritis continues to be an important health problem in childhood, despite the progress in the care of this condition. Therefore, early diagnosis, strict follow-up and appropriate treatment are the pillars of a better evolution(AU)

Risk factors of persistently active disease among Filipino children with systemic juvenile idiopathic arthritis: A 10-year study in a tertiary hospital

@#<p style="text-align: justify;"><strong>Background:</strong> Systemic juvenile idiopathic arthritis (SJIA) is one of the most common subtypes of arthritis among children in southeast Asia with higher progression of disease activity. Unsuccessful control of the disease may lead to long-term disability resulting in functional limitations that would affect productivity of the individual.</p><p style="text-align: justify;"><strong>Objective:</strong> The study determined the risk factors for persistently active disease among Filipino children aged 2 weeks to 18 years diagnosed with SJIA seen in the Section of Pediatric Rheumatology of the University of Santo Tomas Hospital (USTH) from June 2009 to June 2019.</p><p style="text-align: justify;"><strong>Methodology:</strong> A retrospective cohort study was done involving chart review of both clinical division and private division patients. The following parameters were determined: sex, age at diagnosis, time elapsed from symptom onset to diagnosis, joint involvement, inflammatory markers and extraarticular manifestation. Statistical analysis included frequencies, percentages and logistic regression for the risk factors of interest.</p><p style="text-align: justify;"><strong>Results:</strong> One hundred twenty-seven patients with SJIA who were appropriately treated for at least three years were included. Among which, 88 (69%) developed persistently active disease. Among them, 36 (41%) were diagnosed at 1-5 years old. Many were diagnosed (n=54, 61%) after five weeks. The most commonly affected joints were the wrists, knees and ankles. The most common contracture noted involved the cervical joint. Only 33 (26%) patients received biologic agents. Risk factors identified for the development of persistent disease activity were low hemoglobin levels at the time of diagnosis and after one month of treatment, elevated platelet count after a month, substantial joint count after three months and increased ESR after 6 months.</p><p style="text-align: justify;"><strong>Conclusion:</strong> The change or improvement of the joint count and in hemoglobin, platelet count and ESR levels after appropriate treatment may determine the risk for persistently active disease in Filipino children with SJIA.</p>

Trastorno de la alineación de articulaciones metacarpofalángicas en una adolescente con artritis idiopática juvenil / Metacarpophalangeal joint alignment disorder in a teenager diagnosed with juvenile idiopathic arthritis

La artritis idiopática juvenil es una enfermedad inflamatoria, sistémica y crónica que afecta a personas menores de 18 años de edad. Tiene diversas formas clínicas de presentación, pero todas y cada una de ellas pueden causar un elevado número de complicaciones articulares y extraarticulares que pueden desencadenar discapacidad funcional y disminución de la percepción de la calidad de vida relacionada con la salud. Se presenta la imagen poco frecuente de alteraciones de la alineación en las articulaciones metacarpofalángicas de ambas manos en una paciente de 14 años de edad con antecedentes de 3 años de evolución de artritis idiopática juvenil. Se administró tratamiento con esteroides y medicamentos modificadores de la enfermedad. A los 3 meses se encontraba estable, con una escala visual análoga de dolor ocasional de 2 puntos y con esquema terapéutico adecuado para el control de su enfermedad de base(AU)

Juvenile idiopathic arthritis is an inflammatory, systemic and chronic disease that affects people under 18 years of age. It presents various clinical forms of presentation but each and every one of them can generate a high number of joint and extra-articular complications that can trigger functional disability and decrease in the perception of health-related quality of life. There is a rare image of alterations in the alignment at the level of metacarpophalangeal joints of both hands in a 14-year-old patient with a history of three years of evolution of juvenile idiopathic arthritis(AU)

Disfunción temporomandibular en pacientes con síndrome de Sjögren / Temporomandibular dysfunction in patients with Sjögren's syndrome

Introducción: El síndrome de Sjögren es una enfermedad reumática, inflamatoria y crónica caracterizada por dolor articular y resequedad de las mucosas. La articulación temporomandibular (ATM) y las glándulas parótidas y salivales suelen estar afectadas. Objetivo: Determinar la prevalencia de la afectación de la articulación temporomandibular en pacientes con síndrome de Sjögren. Métodos: Estudio básico, no experimental, descriptivo y de corte transversal que incluyó a 78 pacientes con diagnóstico de síndrome de Sjögren atendidos en la Unidad Móvil número 2 de Alausi entre 2017 y 2019. Para identificar la afectación de la ATM se realizaron ecosonografías. Se usó la prueba de correlación de Pearson para establecer la relación entre las características de la enfermedad y la presencia de afectación articular. Resultados: El promedio de edad fue de 46,18 años. Predominaron los pacientes entre 40 y 60 años (62,82 por ciento), el sexo femenino (85,90 por ciento), y el tiempo de evolución de la enfermedad entre 3 y 5 años (50,00 por ciento). El 79,49 por ciento presentó síndrome de Sjögren secundario, y la artritis reumatoide fue la causa más frecuente (54,84 por ciento). El 65,38 por ciento tenía algún tipo de afectación de la ATM, y el hallazgo más común fue la disminución del espacio articular (56,86 por ciento). Conclusiones: Existió una elevada prevalencia de afectación de la ATM en los pacientes con síndrome de Sjögren, y el hallazgo principal fue la disminución del espacio articular. Se encontró una correlación positiva media entre el tiempo de evolución de la enfermedad y la presencia de afectación de la ATM(AU)

Introduction: Sjögren's syndrome is a rheumatic, inflammatory and chronic disease characterized by the presence of joint pain and dryness of the mucous membranes. The temporomandibular joint and the parotid and salivary glands usually have a high frequency of involvement. Objective: To determine the prevalence of temporomandibular involvement in patients with Sjögren's syndrome. Methods: Descriptive, correlational and explanatory study that included 78 patients diagnosed with Sjögren's syndrome treated in the mobile unit number 2 of Alausi. Echocardiography of the temporomandibular joints was performed to identify the involvement of the joint. Pearson's correlation test was used to establish a relationship between the characteristics of the disease and the presence of joint involvement. Results: Average age of 46.18 years with a predominance of patients between 40 and 60 years of age (62.82 percent), of the female sex (85.90 percent) and with time of evolution of the disease between 3 and 5 years (50.00 percent). 79.49 percent of the cases presented secondary Sjögren's syndrome, rheumatoid arthritis being the most frequent disease (54.84 percent). 65.38 percent of the patients presented some type of involvement of the temporomandibular joint, with the decrease in joint space being the most frequent finding (56.86 percent). Conclusions: There was a high prevalence of temporomandibular joint involvement in patients with Sjögren's syndrome, with the decrease in joint space being the finding that was most frequently identified. A positive average correlation was found between the time of evolution of the disease and the presence of temporomandibular joint involvement(AU)

Recomendaciones pediátricas para el manejo de la uveítis no infecciosa en Costa Rica / Pediatric recommendations for the management of non-infectious uveitis in Costa Rica

Resumen Justificación: La uveítis idiopática y la asociada a artritis idiopática juvenil son condiciones oculares que llevan a deterioro visual. En Costa Rica, la incidencia en pediatría se desconoce; aunque existe una clínica especializada en el Hospital Nacional de Niños para el manejo de estas patologías, no hay guías ni recomendaciones de manejo que hayan sido publicadas. Objetivos: Resumir las recomendaciones de manejo vigentes para uveítis no infecciosas y ofrecer una guía adaptada a la realidad costarricense, específicamente para población pediátrica. Métodos: Se efectuó una revisión no sistemática de bibliografía médica indexada en las plataformas PubMed y Scielo, sobre el diagnóstico y manejo de uveítis no infecciosa orientado a población pediátrica y en artritis idiopática juvenil. Se revisaron las guías recomendadas en Europa y se ajustaron a lo que se realiza en la Clínica de Uveítis del Hospital Nacional de Niños. Conclusiones: Se realiza una propuesta de manejo que incluye una valoración oftalmológica oportuna, diagnóstico certero, y tratamiento temprano y agresivo para prevención de complicaciones y minimizar secuelas.

Summary Importance: Idiopathic uveitis and that associated with juvenile idiopathic arthritis are ocular conditions that lead to visual impairment. In Costa Rica, the incidence in pediatric population is unknown; although there is a specialized clinic at the National Children's Hospital for the management of these pathologies, there are no guidelines or recommendations published in our country. Aims: To summarize the current management recommendations for non-infectious uveitis and offer a guide adapted to the Costa Rican reality, specifically for the pediatric population. Methods: A non-systematic review of indexed medical literature on PubMed and Scielo platforms was carried out on the diagnosis and management of non-infectious uveitis aimed to pediatric patients and in juvenile idiopathic arthritis. The recommended guidelines in Europe were reviewed and adjusted to what is done at the Uveitis Clinic of the National Children's Hospital. Conclusions: A management proposal is made that includes a timely ophthalmological evaluation, accurate diagnosis; early and aggressive treatment to prevent complications and minimize sequelae

Cambio de diagnóstico y de categoría diagnóstica en pacientes con artritis idiopática juvenil en 7 años de seguimiento / Change of diagnosis and diagnostic category in patients with juvenile idiopathic arthritis within 7 years of follow-up

Resumen: Introducción: Al menos 50% de los pacientes pediátricos portadores de artritis idiopática juvenil (AIJ) continuará control en reumatología adulto. La clasificación de la Liga Internacional de Asociaciones de Reumatología (ILAR) vigente, actualmente en revisión, difiere de la clasificación de las artritis inflamatorias del adulto. Se ha reportado cambios de categoría en 10,8% de los pacientes durante el seguimiento. Objetivo: Analizar los pacientes con AIJ seguidos al menos 7 años para objetivar cambios de diagnós tico en la transición, e identificar factores de mal pronóstico funcional. Pacientes y Método: Estudio retrospectivo en base a registros clínicos. Se incluyó a la totalidad de los pacientes con AIJ controla dos en policlínico pediátrico del Hospital de Puerto Montt entre el año 2005 y 2017, que cumplieron siete o más años de seguimiento. Se realizó análisis descriptivo en base a variables clínicas: categoría diagnóstica, tiempo de evolución al diagnóstico, actividad clínica y serológica, y tiempo de evolución al inicio de la terapia farmacológica. Resultados: Se evaluaron 18 pacientes, 3 Oligo-articular (OA) persistente, 1 OA extendida, 4 Poli-articular (PA) factor reumatoide (FR) negativo, 4 PA FR positivo, 5 Sistémicas, 1 Psoriática, todos con seguimiento mayor a 7 años. Once de 18 niños fueron transfe ridos a adultos. Tres de 11 cambiaron de diagnóstico a Artritis Reumatoide (AR) más otra enferme dad autoinmune: Síndrome de Sjögren + Lupus eritematoso sistémico, Púrpura trombocitopénico inmune, Enfermedad autoinmune no clasificada y cinco de 11 niños de categoría ILAR: OA a Artritis reumatoide juvenil, OA extendida a PA FR negativo, 3 Sistémicas a PA FR negativo. Edad de inicio, formas poli-articulares, retrasos en diagnóstico y comienzo de terapia se asociaron a secuelas e infla mación persistente. Conclusiones: Ocho de once pacientes transferidos cambiaron denominación diagnóstica y/o presentaron otras enfermedades autoinmunes. Algunos factores de mal pronóstico deben mejorar.

Abstract: Introduction: At least 50% of pediatric patients with Juvenile Idiopathic Arthritis (JIA) will require continued fo llow-up in adult rheumatology. The present International League of Associations for Rheumatology (ILAR) classification, currently under revision, differs from its classification of inflammatory arthritis in adults. Category changes have been reported in 10.8% of patients during follow-up. Objective: To analyze JIA patients in follow-up for at least 7 years to detect diagnosis changes during transition to adult care, identifying factors of poor functional prognosis. Patients and Method: Retrospective study based on medical records of JIA patients seen at the pediatric polyclinic of the Puerto Montt Hospital between 2005 and 2017, who were monitored for at least 7 years. Descriptive analysis was performed according to clinical variables: diagnostic category, evolution before diagnosis, clinical and serological activity, and evolution before starting drug therapy. Results: We evaluated 18 pa tients, corresponding to 3 patients with persistent oligoarticular arthritis (OA), 1 with extended OA, 4 with polyarticular arthritis (PA) rheumatoid factor (RF) negative, 4 with PA RF positive, 5 with syste mic JIA, and 1 with psoriatic arthritis, all have had follow-up more than 7 years. 11 out of 18 patients transitioned to adult care. Three out of 11 patients changed diagnosis to Rheumatoid Arthritis (RA) plus another autoimmune disease such as Sjögren's Syndrome + Systemic Lupus Erythematosus, Immune thrombocytopenia, or unclassified autoimmune disease, and 5 out of 11 children changed ILAR category from OA to Juvenile Rheumatoid Arthritis, extended OA to PA RF negative, and 3 from Systemic arthritis to PA RF negative. Age of onset, polyarticular forms, delay in diagnosis, and the start of therapy were associated with sequelae and persistent inflammation. Conclusions: Eight of the eleven JIA patients who transitioned to adult care changed their diagnosis or presented other autoimmune diseases. Some factors of poor prognosis must improve.