Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study.

OBJECTIVES: Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA. METHODS: We conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0-24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA. RESULTS: We included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0-24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0-6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA. CONCLUSIONS: The novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.

Infant gut microbiota and environment associate with juvenile idiopathic arthritis many years prior to disease onset, especially in genetically vulnerable children.

BACKGROUND: The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a prospective birth cohort to assess disease risk. METHODS: Data was collected from the All Babies in Southeast Sweden (ABIS) population-based cohort (n = 17,055), 111 of whom later acquired JIA (ABISJIA). Stool samples were collected at one year of age for 10.4%. To determine disease association, 16S rRNA gene sequences were analyzed, with and without confound adjustment. Genetic and environmental risks were assessed. FINDINGS: ABISJIA had higher abundance of Acidaminococcales, Prevotella 9, and Veillonella parvula and lower abundance of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis, and Akkermansia muciniphila (q's < 0.05). Parabacteroides distasonis greatly increased the odds of later contracting JIA (OR = 6.7; 1.81-24.84, p = 0.0045). Shorter breastfeeding duration and increased antibiotic exposure compounded risk in a dose-dependent manner, especially in those with genetic predisposition. INTERPRETATION: Microbial dysregulation in infancy may trigger or accelerate JIA development. Environmental risk factors have a stronger impact on genetically predisposed children. This study is the first to implicate microbial dysregulation in JIA at such an early age, with many bacterial taxa associated with risk factors. These findings provide opportunities for intervention or early screening and offer new insights into JIA pathogenesis. FUNDING: Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping.

Tumors Constitute a Majority of Total Knee Arthroplasty in Patients <21 Years Old: A United States Nationwide Analysis.

BACKGROUND: Total knee arthroplasty (TKA) is rarely performed in patients under 21 years old, but the frequency of utilization of TKA in this population in the United States is not known. The purpose of this study was to evaluate trends in the use of TKA in patients <21 in the United States. Additionally, we aimed to determine the characteristics of these patients and the hospitals in which this procedure is performed. METHODS: We retrospectively reviewed the Kids' Inpatient Database, a national weighted sample of all inpatient hospital admissions in the United States in patients <21 years of age. We used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify patients undergoing TKA from 2000 to 2019 and determine a primary diagnosis. Descriptive statistics were calculated using the appropriate sample weights. RESULTS: The total weighted number of TKAs performed in patients <21 years from 2000 to 2019 was 1,535. There were 70.9% of TKAs performed for a primary diagnosis of tumor, and the use of TKA for malignant tumors has increased. In contrast, the use of TKA for inflammatory arthritis/juvenile idiopathic arthritis decreased significantly over the study period. The majority of TKAs were performed in urban teaching hospitals with a large bed size. CONCLUSION: Approximately 1,535 TKAs have been performed in patients <21 years from 2000 to 2019 in the United States. The majority of these procedures were performed for reconstruction after resection of a malignant tumor. The rate of TKA for inflammatory arthritis/juvenile idiopathic arthritis has decreased over the past two decades.

Early intra-articular corticosteroid injection is predictors of remission of juvenile idiopathic arthritis.

BACKGROUND: The aim of this study was to assess predictors of remission in children with juvenile idiopathic arthritis (JIA), treated with intra-articular corticosteroid injection (IACI) as monotherapy or in combination with methotrexate (MTX). METHODS: A retrospective study of 43 patients diagnosed with different JIA subtypes and followed-up at a tertiary center between 2000 and 2014. We included patients treated with IACI as monotherapy or in combination with MTX at onset or thereafter. We excluded patients treated with MTX as monotherapy or in combination with biologics. Patients were divided into two groups on the basis of assigned treatment. Primary outcomes were disease remission and duration. We performed descriptive analysis, bivariate analysis and cross-correlation analysis between variables. Statistically significant results (P value <0.05) were chosen as variables for multivariate analysis. RESULTS: Median age of onset was 4.56 years (SD±3.85). Median time between disease onset and first IACI was 16.9 months (SD±34.7). We evaluated between time to remission in relation to age, time interval between onset and first IACI, time between onset and start of treatment with MTX, and time between first and second IACI. All of these were statistically significant (P value <0.05) in bivariate analysis, but time between onset and first IACI was the only statistically significant result, using multiple linear regression analysis. Therefore, in our study, 37 patients (86%) of patients went into remission on medication after a median disease duration of 48.8 months. CONCLUSIONS: We found that remission was related to time between onset and first IACI. Our predictive model showed that early IACI can be considered as a strong predictor of remission.

Temporal Relationship Between Juvenile Idiopathic Arthritis Disease Activity and Uveitis Disease Activity.

OBJECTIVE: To determine whether there is a temporal association between arthritis and uveitis activity among children with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS: Uveitis and arthritis data from patients with JIA-U age ≤21 years were collected from July 2013 to December 2019 at a tertiary care center. Arthritis activity was assessed at each rheumatology visit, and the primary outcome was the presence of active uveitis at ophthalmologic examination within 45 days of the rheumatology visit. Repeated-measures logistic regression was used to evaluate the temporal association between any uveitis activity within 45 days of arthritis activity. Models were adjusted for demographic-, disease-, and treatment-related factors. RESULTS: A total of 98 patients were included: 81 (83%) female, 67 (69%) antinuclear antibody positive, 59 (60%) oligoarticular, and 13 (13%) enthesitis-related arthritis (ERA) subtypes. There were 1,229 rheumatology visits, with a median of 13 visits per patient (interquartile range 7-18). Concordance between arthritis and uveitis activity was observed 73% of the time (694 of 947). There was an independent temporal association between uveitis and arthritis activity (odds ratio 2.47 [95% confidence interval 1.72-3.54]; P < 0.01), adjusted for demographic and disease characteristics. Use of combination biologic and nonbiologic disease-modifying antirheumatic drugs, female sex, HLA-B27 positivity, and ERA and polyarticular (rheumatoid factor negative) subtypes were associated with decreased odds of active uveitis at any time point. CONCLUSION: In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity. These novel results suggest that an arthritis flare should prompt an expedited referral to the ophthalmologist.

Moving from nature to nurture: a systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

OBJECTIVES: JIA is the most common paediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanism and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: Four databases (MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to January 2020. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes 66 environmental factors from 39 studies (11 cohort and 28 case-control studies) over 45 years. Study sample sizes ranged from 41 to 1.9 million participants. Eight environmental factors from ten studies were meta-analysed. Caesarean section delivery was associated with increased JIA risk [pooled odds ratio (OR) 1.11, 95% CI: 1.01, 1.22]. Conversely, presence (vs absence) of siblings (pooled OR 0.60, 95% CI: 0.44, 0.81) and maternal prenatal smoking (pooled OR 0.70, 95% CI: 0.58, 0.84) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research undertaken over five decades. We also highlight the challenges of combining data collected over this period due to limited between study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study.

BACKGROUND: The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA. METHODS: In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors. RESULTS: Exposure to antibiotics during the periods 1-12 months, 1-3 years and 5-8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11-9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36-3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15-2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment. The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA. CONCLUSIONS: Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.

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)

Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches.

Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.

Association of HLA-G, HLA-E and HLA-B*27 with susceptibility and clinical phenotype of enthesitis related arthritis (ERA).

We studied the association of Enthesitis related arthritis (ERA) the most common variant of juvenile idiopathic arthritis (JIA) in Asians, with HLA-G and -E polymorphisms. HLA-G (14 bp Ins/Del rs371194629, +3142 rs1063320, +3187 rs9380142) and HLA-E (rs1264457, and rs2844724) polymorphisms were analyzed in 127 patients with ERA and 381 ethnically matched healthy controls with TaqMan 5'-nuclease assay using allele-specific fluorogenic oligonucleotide probes. HLA-G and -E polymorphisms were not found to be associated with susceptibility to ERA. HLA-G +3187 (rs9380142) G allele was associated with hip arthritis (Pc = 0.04, OR = 2.22, 95%CI = 1.07-4.63) and hip deformity (Pc = 0.02, OR = 2.51, 95%CI = 1.16-5.43). HLA-B*27 was positive in 91. HLA-E rs1264457 G and rs2844724 T alleles may be associated with B*27 positivity in ERA. Among HLA-G, -E haplotypes, frequency of -InsGAAC was significantly higher in patients than healthy controls (Pc = 0.003). In conclusion, HLA-G and HLA-E haplotype -InsGAAC may be associated with susceptibility to ERA and HLA-G +3187 rs9380142 A>G polymorphism may be a poor prognostic marker for progression to hip arthritis and deformity in ERA-JIA.

Nutri-epigenetics: the effect of maternal diet and early nutrition on the pathogenesis of autoimmune diseases.

Autoimmune diseases comprise a wide group of diseases involving a self-response of the immune system against the host. The etiopathogenesis is very complex involving disease-specific factors but also environmental factors, among which the diet. Maternal diet during pregnancy as well as early nutrition recently attracted the interest of the scientists as contributing to the immune programming. In this paper, we reviewed the most recent literature on the effect of maternal diet and early nutrition in modulating the immune system in a selected subset of autoimmune diseases: type 1 diabetes, celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis and rheumatoid arthritis. Particularly, we focused our narrative on the role of maternal and perinatal nutrition in the epigenetic mechanisms underlying the auto-immune response. Maternal diet during pregnancy as well as breastfeeding and early nutrition play a big role in many epigenetic mechanisms. Most of the nutrients consumed by the mother and the infant are known exerting epigenetic functions, such as folate, methionine, zinc, vitamins B12 and D, fibers, casein and gliadin, and they were linked to gene expression changes in the immune pathways. Despite the common role of maternal diet, breastfeeding and early nutrition in almost all the autoimmune diseases, each disease seems to have specific diet-driver epigenetic mechanisms that require further investigations. The research in this field is opening new routes to establishing a precision nutrition approach to the auto-immune diseases.

Do geography and ethnicity play a role in juvenile Spondyloarthritis? A multi-center binational retrospective study.

BACKGROUND: Observations among Israeli pediatric rheumatologists reveal that pediatric Juvenile Spondyloarthritis (JSpA) may present differently compared to patients from the United States (US). This study is aimed to compare the demographic and clinical variables of Israeli and US JSpA patients upon presentation. METHODS: We performed a retrospective, cross-sectional, multicenter comparison of JSpA patients among 3 large Israeli pediatric rheumatology centers and a large US pediatric rheumatology center. Patients with diagnosis of Juvenile Ankylosing Spondylitis (JAS) and/or Enthesitis-related Arthritis (ERA) were included. The demographic, clinical and radiologic features were compared. RESULTS: Overall 87 patients were included (39 Israeli, 48 US patients). Upon presentation, inflammatory back pain, sacroiliac joint tenderness and abnormal modified Schober test, were significantly more prevalent among Israeli patients (59% vs. 35.4, 48.7% vs. 16.7, and 41.2% vs. 21.5%, respectively, all p < 0.05), whereas peripheral arthritis and enthesitis were significantly more prevalent among US patients (43.6% vs. 91.7 and 7.7% vs. 39.6% in Israeli patients vs. US patients, p < 0.05). In addition, 96.7% of the Israeli patients versus 29.7% of the US patients demonstrated sacroiliitis on MRI (p < 0.001, N = 67). Less than one-third of the Israeli patients (32%) were HLA-B27 positive vs. 66.7% of US patients (p = 0.007). CONCLUSION: Israeli children with JSpA presented almost exclusively with axial disease compared to US patients who were more likely to present with peripheral symptoms. HLA B27 prevalence was significantly lower in the Israeli cohort compared to the US cohort. Further studies are needed to unravel the genetic and possibly environmental factors associated with these findings.

Neutrophils Lose the Capacity to Suppress T Cell Proliferation Upon Migration Towards Inflamed Joints in Juvenile Idiopathic Arthritis.

Neutrophils are highly abundant in synovial fluid of rheumatic inflamed joints. In oligoarticular juvenile idiopathic arthritis (JIA), synovial fluid neutrophils have impaired effector functions and altered phenotype. We hypothesized that these alterations might impact the immunoregulatory interplay between neutrophils and T cells. In this study we analyzed the suppressive effect of neutrophils, isolated from blood and synovial fluid of oligoarticular JIA patients, on CD4+ T cells activated by CD3/CD28 stimulation. JIA blood neutrophils suppressed T cell proliferation but synovial fluid neutrophils from several patients did not. The loss of T cell suppression was replicated in an in vitro transmigration assay, where healthy control neutrophils migrated into synovial fluid through transwell inserts with endothelial cells and synoviocytes. Non-migrated neutrophils suppressed proliferation of activated CD4+ T cells, but migrated neutrophils had no suppressive effect. Neutrophil suppression of T cells was partly dependent on reactive oxygen species (ROS), demonstrated by impaired suppression in presence of catalase. Migrated neutrophils had reduced ROS production compared to non-migrated neutrophils. A proteomic analysis of transwell-migrated neutrophils identified alterations in proteins related to neutrophil ROS production and degranulation, and biological processes involving protein transport, cell-cell contact and inflammation. In conclusion, neutrophils in synovial fluid of children with JIA have impaired capacity to suppress activated T cells, which may be due to reduced oxidative burst and alterations in proteins related to cell-cell contact and inflammation. The lack of T cell suppression by neutrophils in synovial fluid may contribute to local inflammation and autoimmune reactions in the JIA joint.

Presentation of a case of Bruton type primary agammaglobulinemia in Guinea.

X-linked agammaglobulinemia (XLA) is a rare genetic disease caused by a mutation in the Bruton tyrosine kinase (BTK) gene. It is characterized by a profound deficiency of B cells and a decrease in all classes of immunoglobulins (Ig). We report one case in a 3-year-old boy seen for recurrent acute otitis media, perineal abscess, oligoarthritis. The serum immunoglobulin (Ig) assay showed an IgG level of 0.6g/l. IgM and IgA are indosable. Marrow immunophenotyping showed an absence of precursor B less than 1%. Molecular biology confirmed Burton's disease (stop mutation, C37C) in exon 2 of the BTK gene. Treatment with intravenous immunoglogulin was started.

Juvenile â€Å“idiopathic†arthritis (JIA) as a manifestation of food allergy. Case study.

Studies linking type of diet and juvenile idiopathic arthritis (JIA) have variable results and are inconsistent. This case shows an evolution which fulfilled the criteria of JIA, but was diagnosed as food allergy. Case: A seven-year old boy had fever, arthralgia, general malaise, headaches, abdominal pain and rashes. These symptoms were diagnosed as fever of unknown origin (FUO) and probable JIA. There was a stabbing pain in the right iliac fossa. An upper and lower endoscopy were performed and nodular ileocolitis was detected. A hypoallergenic diet was prescribed, in addition to mesalazine and oral corticosteroids. The patient was asymptomatic for 2.5 months and then relapsed with all symptoms after consuming dairy. This JIA case shows the diagnostic phases of food allergy: improvement and recurrence of symptoms with the reintroduction of the allergen (oral challenge=gold standard of food allergy). There is evidence that supports the existence of a gut-joint axis, where the luminal content triggers a series of immunologically mediated reactions that can cause systemic diseases such as J other connective tissue diseases. This case report adds reasonable evidence in support of food allergy as a cause of JIA.

Assessment and treatment of Down syndrome-associated arthritis: a survey of pediatric rheumatologists.

BACKGROUND: Inflammatory arthritis in children with Down syndrome (DS) was first described in 1984 and is now termed Down syndrome-associated arthritis (DA). Studies have shown that DA is under-recognized with a 19-month average delay in diagnosis. Additionally, most patients present with polyarticular, rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative disease. Current therapies for juvenile idiopathic arthritis (JIA) have been used, but appear to be poorly tolerated, more toxic and less effective in patients with DA. There is currently no standardized approach to the assessment or management of DA. The objective of this study was to describe provider perspectives toward diagnostic and treatment approach of DA, to provide baseline information upon which to design future studies. METHODS: An electronic survey, organized into sections regarding individual practices of assessment and treatment approach of DA, was sent to the Pediatric Rheumatology electronic list-serv. Survey responses were voluntary and results were analyzed by descriptive statistics. RESULTS: Of 90 survey responses received, 89 were included in the analysis (one was a duplicate response). The respondents were mostly pediatric rheumatologist (94%), with greater than 10 years of experience (55%). The majority (64%) currently see 1-3 patients with DA. Most view DA as the same disease as JIA (73%), and the majority (63%) use a combination of history, exam and imaging to diagnose DA. The most ordered diagnostic tests are CBC (97%) and ESR (96%). The most used treatments include NSAIDs (94%) and methotrexate (91%) followed by anti-TNF agents (90%). Methotrexate is most administered by subcutaneous route (84%) at a dose of 15 mg/m2 (56%). Oral corticosteroids were only used in 19% of the patients with DA. CONCLUSION: This is the first study to evaluate provider perspectives towards the diagnostic and treatment approach of DA. Most pediatric rheumatologists feel that DA and JIA are synonymous, and similar approaches to diagnosis are employed, utilizing history, physical exam, laboratory tests, and imaging modalities. DA is treated similarly to JIA with initiation of NSAIDs, disease-modifying anti-rheumatic drugs and biologic therapy. More research is needed to determine optimal screening and therapeutic approach specific to DA.

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate.

OBJECTIVES: Long-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment. METHODS: Children aged 4-17 years with polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1). RESULTS: Of 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart failure-related AEs, demyelinating disease, lupus-like syndrome, malignancies, tuberculosis or deaths were reported. JIA ACR 30/50/70/90 responses and JADAS27 LDA were achieved in 66% to 96% of patients at week 104, and 63 (37%) patients achieved clinical remission (JADAS27 ID sustained for ≥6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis). CONCLUSIONS: Through 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.

Juvenile idiopathic arthritis in infants with Harlequin Ichthyosis: two cases report and literature review.

BACKGROUND: Harlequin Ichthyosis is the most severe variant of congenital autosomal recessive ichthyosis, associated with severe morbidity and potentially lethal in early life. At birth, patients present thick and plaque-like scales all over the body, with consequent cutaneous and extra-cutaneous complications, such as poor thermoregulation, recurrent infections, pain, electrolytes imbalance and joint contractures. Juvenile Idiopathic Arthritis usually manifests before the age of 16 years and persists for more than 6 weeks. The association between these two pathologies has been described in the literature as a very rare event, which creates diagnostic and therapeutic challenge. CASE PRESENTATION: We describe two patients affected by Harlequin Ichthyosis who early developed Juvenile Idiopathic Arthritis. Both patients were treated with retinoids, ibuprofen and long-acting intra-articular glucocorticoids; due to polyarticular involvement, one child was also treated with weekly oral methotrexate. CONCLUSIONS: The association between Harlequin Ichthyosis and Juvenile Idiopathic Arthritis is rare and the pathophysiological mechanism that binds them is still unknown. Nonetheless caregivers should be aware of the possible occurrence of Juvenile Idiopathic Arthritis at very early ages in children affected by Harlequin Ichthyosis.

Juvenile "idiopathic" arthritis (JIA) as a manifestation of food allergy. Case Study / Alergia alimentaria artritis reumatoidea juvenil. Reporte de un caso

ABSTRACT Studies linking type of diet and juvenile idiopathic arthritis (JIA) have variable results and are inconsistent. This case shows an evolution which fulfilled the criteria of JIA, but was diagnosed as food allergy. Case: A seven-year old boy had fever, arthralgia, general malaise, headaches, abdominal pain and rashes. These symptoms were diagnosed as fever of unknown origin (FUO) and probable JIA. There was a stabbing pain in the right iliac fossa. An upper and lower endoscopy were performed and nodular ileocolitis was detected. A hypoallergenic diet was prescribed, in addition to mesalazine and oral corticosteroids. The patient was asymptomatic for 2.5 months and then relapsed with all symptoms after consuming dairy. This JIA case shows the diagnostic phases of food allergy: improvement and recurrence of symptoms with the reintroduction of the allergen (oral challenge=gold standard of food allergy). There is evidence that supports the existence of a gut-joint axis, where the luminal content triggers a series of immunologically mediated reactions that can cause systemic diseases such as JIA and other connective tissue diseases. This case report adds reasonable evidence in support of food allergy as a cause of JIA.

RESUMEN Los estudios que relacionan el tipo de dieta y la artritis idiopática juvenil (AIJ) tienen resultados variables y son inconsistentes. Este caso muestra una evolución que cumplió con los criterios de AIJ, pero fue diagnosticada como alergia alimentaria. Caso: Un niño de siete años tenía fiebre, artralgia, malestar general, dolores de cabeza, dolor abdominal y erupciones cutáneas. Estos síntomas fueron diagnosticados como fiebre de origen desconocido (FUO) y probable AIJ. Hubo un dolor punzante en la fosa ilíaca derecha. Se realizó una endoscopia superior e inferior y se detectó ileocolitis nodular. Se prescribió una dieta hipoalergénica, además de mesalazina y corticosteroides orales. El paciente estuvo asintomático durante 2,5 meses y luego recayó con todos los síntomas después de consumir lácteos. Este caso de AIJ muestra las fases diagnósticas de la alergia alimentaria: mejora y recurrencia de los síntomas con la reintroducción del alergeno (desafío oral = estándar de oro de alergia alimentaria). Existe evidencia que respalda la existencia de un eje de la articulación intestinal, donde el contenido luminal desencadena una serie de reacciones inmunológicamente mediadas que pueden causar enfermedades sistémicas como la AIJ y otras enfermedades del tejido conectivo. Este informe del caso agrega evidencia razonable en apoyo de la alergia a los alimentos como causa de AIJ.