Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests.

OBJECTIVE: To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA). STUDY DESIGN: In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age. RESULTS: In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate. CONCLUSIONS: The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.

Abdominal pain in Finnish young adults with juvenile idiopathic arthritis.

OBJECTIVES: Abdominal pain (AP) is a common feature in the general population. However, in patients with juvenile idiopathic arthritis (JIA) AP has scantily been studied. Among other reasons, gastrointestinal symptoms may present as side effects due to the medical treatment of JIA. The aim of the study was to explore the frequency of AP and its relationship to disease components and health-related quality of life (HRQoL) among young adults with JIA. METHODS: This study included a cohort of 97 Finnish patients belonging to the population-based Nordic JIA cohort at their 17-year follow-up study visit. Mean age of the patients was 23 years. AP, functional status, fatigue, HRQoL, disease characteristics of JIA, and comorbidities were evaluated. AP was classified into three categories according to frequency: (1) never, (2) seldom (one to three times a month) and (3) frequent (at least once a week). RESULTS: About 48 (50%) young adults with JIA reported AP. Seldom AP was reported by 37 (38%), and frequent AP by 11 (11%) patients. AP was significantly associated with fatigue, female gender, functional status and arthritis-related pain. Patients having frequent AP reported lower HRQoL. AP was associated with the use of methotrexate and sulfasalazine, but not with nonsteroidal anti-inflammatory drugs (NSAIDs). CONCLUSION: AP is an important complaint in young adults with JIA and is associated with fatigue, female gender, methotrexate and sulfasalazine use. Patients with JIA reporting frequent AP with lower functional status and higher arthritis-related pain values have lower HRQoL.

Uveitis in Juvenile Idiopathic Arthritis: 18-Year Outcome in the Population-based Nordic Cohort Study.

PURPOSE: To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). DESIGN: Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA. PARTICIPANTS: A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden. METHODS: Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data. MAIN OUTCOME MEASURES: Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications. RESULTS: Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12. CONCLUSIONS: Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.

Systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome due to a CASP1 variant causing inflammasome hyperactivation.

OBJECTIVES: We investigated a patient with systemic juvenile idiopathic arthritis (sJIA) and recurrent macrophage activation syndrome (MAS) to discover genetic and immunological contributing factors. METHODS: Severe recurrent MAS motivated whole exome sequencing (WES) to identify genetic variants potentially involved in disease pathogenesis. In vitro peripheral blood mononuclear cell (PBMC) stimulations for cytokine expression and caspase-1 activity assays as well as NF-κB reporter luciferase assays were performed to functionally characterize variants. RESULTS: WES revealed an extremely rare heterozygous missense variant, c.482G>A, p.R161H in the CASP1 gene encoding pro-caspase-1. Lipopolysaccharide (LPS) stimulation of patient PBMCs induced high levels of IL-6 compared to controls, and activation of the NLRP3 inflammasome resulted in increased production of IL-1ß and IL-18 as well as significantly elevated caspase-1 activity. Constitutive and inducible levels of IL-18 and IFNγ in whole blood were markedly elevated. Expression of the CASP1 variant in an NF-κB reporter luciferase assay induced increased NF-κB activation in a RIP2-dependent manner. The disease course of the patient was complicated by severe recurrent MAS. However, dual IL-1 and IL-6 blockade caused disease remission. CONCLUSION: For the first time, we demonstrate the involvement of a CASP1 variant in sJIA and recurrent MAS. This variant is gain-of-function for both inflammasome and NF-κB activation leading to increased production of IL-6, IL-1ß and IL-18. Although dual IL-1 and IL-6 blockade may be beneficial in patients, in whom single treatment is not sufficient to control MAS, caution should be practiced, since interstitial lung disease may progress despite apparent clinical and biochemical remission.

The Danish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Danish language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 303 JIA patients (7.9% systemic, 35% oligoarticular, 22.1% RF negative polyarthritis, 35% other categories) and 99 healthy children, were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Danish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Clinical Outcome and Long-term Remission in JIA.

PURPOSE OF REVIEW: This review assesses the long-term remission and predictors of clinical outcome in patients with juvenile idiopathic arthritis (JIA). A comprehensive literature search was performed including articles published between January 1, 2004 and February 28, 2017. Studies, with a minimum follow-up of 24 months, were selected independently by two reviewers based on in- and exclusion criteria. The objective outcome was inactive disease/clinical remission as defined by the Wallace criteria at last follow-up. RECENT FINDINGS: The probability of achieving inactive disease and/or clinical remission is dependent on the JIA subcategories studied in the different articles. Overall, a significant proportion of JIA patients still showed signs of active disease at last follow-up. Some studies include patient populations followed for 15 years or more and these patients were exposed to different treatment protocols at disease presentation than patients diagnosed in the biologic era. Although the severity of the morbidity and associated mortality risk has decreased over time, a significant proportion of the current JIA patients still do not reach an inactive disease status within a 2-year follow-up window. Studying the long-term outcome of patients with JIA remains challenging due to the heterogeneity of the study designs and study populations. Although improvement has been shown in the biologic era, we still need to enhance the number of patients with inactive disease within the first 2 years after diagnosis.

Methotrexate Intolerance in Juvenile Idiopathic Arthritis: Definition, Risks, and Management.

Juvenile idiopathic arthritis is the most common rheumatic disorder in childhood and adolescence posing a significant threat of short-term and long-term disability if left untreated. Methotrexate is a folic acid analog with various immunomodulatory properties. It has demonstrated significant efficacy for the treatment of juvenile idiopathic arthritis, often considered the preferred first-line disease-modifying anti-rheumatic drug given as monotherapy or in combination with biological drugs. Despite this, there is a considerable risk for treatment disruptions owing to the high prevalence of methotrexate intolerance, with symptoms such as nausea, stomach ache, vomiting, and behavioral symptoms. Many different risk factors for the intolerance have been proposed including gender, age, disease activity, treatment duration, dosing and administration, and genetic and psychological factors. As the studies have shown contradictory results, many questions are left unanswered. Therefore, a consensus regarding outcome measures and reporting is crucial. In this review, we describe the identification and assessment of methotrexate intolerance and evaluate potential risk factors, genetic associations as well as management strategies.

Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort.

OBJECTIVES: To identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution of the cJADAS10 components and explore characteristics associated with active disease at the 18-year follow-up. METHODS: Patients with onset of JIA in 1997-2000 were followed for 18 years in the population-based Nordic JIA cohort. We used a discrete mixture model for longitudinal clustering of the cJADAS10 and its components. We assessed factors potentially associated with higher scores on the patient's global assessment of well-being (PaGA) by hierarchical clustering and correlation analysis. RESULTS: Four disease activity trajectories were identified based on the cJADAS10 components among 427 patients. In trajectory-group 2, the PaGA and the physician's global assessment of disease activity (PhGA) increased significantly during the course, but not the active joint count. The increase in the PaGA was significantly higher than the increases in the PhGA and the active joint count (p<0.0001). A similar pattern was found among all the patients with active disease in the total cohort. Patients with higher PaGA scores had unfavourable scores on several other patient-reported outcomes. CONCLUSIONS: We have identified groups of patients based on long-term disease activity trajectories. In our study the PaGA was the most important driver of disease activity into adulthood assessed by cJADAS10. We need to better understand how our patients interpret global well-being and implement strategies to achieve inactive disease perceived both by the patient and the physician.

Inflammatory biomarkers predicting long-term remission and active disease in juvenile idiopathic arthritis: a population-based study of the Nordic JIA cohort.

OBJECTIVES: To assess the ability of baseline serum biomarkers to predict disease activity and remission status in juvenile idiopathic arthritis (JIA) at 18-year follow-up (FU) in a population-based setting. METHODS: Clinical data and serum levels of inflammatory biomarkers were assessed in the longitudinal population-based Nordic JIA cohort study at baseline and at 18-year FU. A panel of 16 inflammatory biomarkers was determined by multiplexed bead array assay. We estimated both univariate and multivariate logistic regression models on binary outcomes of disease activity and remission with baseline variables as explanatory variables. RESULTS: Out of 349 patients eligible for the Nordic JIA cohort study, 236 (68%) had available serum samples at baseline. We measured significantly higher serum levels of interleukin 1ß (IL-1ß), IL-6, IL-12p70, IL-13, MMP-3, S100A9 and S100A12 at baseline in patients with active disease at 18-year FU than in patients with inactive disease. Computing receiver operating characteristics illustrating the area under the curve (AUC), we compared a conventional prediction model (gender, age, joint counts, erythrocyte sedimentation rate, C reactive protein) with an extended model that also incorporated the 16 baseline biomarkers. Biomarker addition significantly improved the ability of the model to predict activity/inactivity at the 18-year FU, as evidenced by an increase in the AUC from 0.59 to 0.80 (p=0.02). Multiple regression analysis revealed that S100A9 was the strongest predictor of inactive disease 18 years after disease onset. CONCLUSION: Biomarkers indicating inflammation at baseline have the potential to improve evaluation of disease activity and prediction of long-term outcomes.

Body mass index is associated with health-related quality of life and disease characteristics in young adults with juvenile idiopathic arthritis.

BACKGROUND: There is a growing interest concerning the relationship between obesity and several medical conditions and inflammation. Nevertheless, there is a lack of studies regarding body mass index (BMI) among patients with juvenile idiopathic arthritis (JIA). Our aim was to investigate the impact of BMI on health-related quality of life (HRQoL) measured with a 36-Item Short Form Survey (SF-36), disease activity, and disability in young adults with JIA. METHODS: This study is a part of the population-based Nordic JIA cohort study. All newly diagnosed patients with JIA were recruited consecutively between 1997-2000 in specific regions in the Nordic countries. Patients in this sub-study were enrolled from 434 patients who attended their 18-year follow-up visit. Patients were classified according to the World Health Organization (WHO) into four groups based on their BMI. HRQoL, disease characteristics, disability, fatigue, sleep quality, physical activity, pain, comorbidities, and social status were assessed. RESULTS: Three hundred fifty-five patients from the original study cohort were enrolled in this study and 72% of them were female. Mean age was 23.9 (± SD 4.4) years. A significant relationship was found between the JIA categories and BMI groups (p = 0.014). A significant relationship was also found between BMI and disease activity scores (DAS28) (p = 0.028), disability (p < 0.001), pain (p = 0.013), fatigue (p = 0.035), and sleep quality (p = 0.044). Moreover, a significant relationship between BMI and HRQoL regarding bodily pain (p = 0.010) and general health (p = 0.048) was revealed when adjusted for sex, age, and JIA subtype. CONCLUSION: We discovered that BMI was significantly related to HRQoL, disease activity, and disability. BMI deserves more attention considering the treatment options and outcome of JIA in young adults.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

Tubulointerstitial nephritis in a patient with probable autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is caused by a nonmalignant defective Fas-mediated apoptosis. The main clinical manifestations are chronic lymphadenopathy, splenomegaly, and autoimmune cytopenia. Most patients with ALPS have a FAS germline mutation. ALPS has occasionally been associated with glomerulonephritis and we present the first report of tubulointerstitial nephritis associated with probable ALPS. A 5-year-old girl presented with fever, vomiting, hypertension, and azotemia. No autoantibodies, viral, or streptococcal antibodies were detected. A renal biopsy showed small-vessel vasculitis with normal glomeruli and inflammation in the interstitium. The patient responded to prednisolone treatment and obtained a full renal recovery. Symptoms of connective tissue disorder supervened and after the development of more pronounced splenomegaly, a diagnosis of ALPS was confirmed.

Biologic switching patterns among children with non-systemic juvenile idiopathic arthritis.

BACKGROUND: In juvenile idiopathic arthritis (JIA) clinical remission is unattainable in some patients despite modern biologic disease-modifying antirheumatic drugs (bDMARD) therapy and switching bDMARD is required. The best choice of second-line bDMARD remains unclear. This retrospective observational study aims to describe the pattern, timing, frequency, and reasons for bDMARD switching among children diagnosed with non-systemic JIA. METHODS: Patients were identified by combining unique personal identification numbers, the International Code of Diagnosis (ICD10) for JIA and biologic therapy. Clinical characteristics were collected retrospectively from the electronic medical records. Included were 200 children diagnosed with non-systemic JIA initiating their first biologic drug between January 1st, 2012, and March 1st, 2021. We compared characteristics of non-switchers vs switchers and early switchers (≤ 6 months) vs late switchers (> 6 months). RESULTS: The median age at diagnosis was 7.7 years. We found that 37% switched to a different bDMARD after a median age of 6.3 years after diagnosis. In total, and 17.5% of patients switched at least twice, while 6% switched three or more times. The most common reason for switching was inefficacy (57%) followed by injection/infusion reactions (15%) and uveitis (13%). 77% were late switchers, and switched primarily due to inefficacy. All patients started a tumor necrosis factor inhibitor (TNFi) as initial bDMARD (Etanercept (ETN): 49.5%, other TNFis: 50.5%). The patients who started ETN as first-line bDMARD were more likely to be switchers compared to those who started another TNFi. CONCLUSION: During a median 6.3-year follow-up biologic switching was observed in more than one third, primarily due to inefficacy.

Synovial fibroblasts in juvenile idiopathic arthritis: A scoping review.

Synovial fibroblasts and their role in juvenile idiopathic arthritis have received limited attention compared to other immune mediated disease such as rheumatoid arthritis. Furthermore, no review exists regarding synovial fibroblasts, their interaction with immune cells and their potential involvement in juvenile idiopathic arthritis pathogenesis. This scoping review set out to identify and compile the current knowledge of all peer-reviewed studies on synovial fibroblasts from patients with juvenile idiopathic arthritis. The aim was to map the current knowledge and to produce a tool to assist future studies. The entire MEDLINE, EMBASE and Web of Science databases were used to identify all published studies in English regarding synovial fibroblasts from patients with juvenile idiopathic arthritis. We identified 18 eligible studies out of a total of 1778 screened entries. The majority of studies identified synovial fibroblast subsets or functional characteristics that may be involved in disease pathogenesis. We identified mechanisms of cell-cell interaction with leukocytes, pro-inflammatory signaling and unfavorable connective tissue homeostasis that may contribute to cartilage damage or bony overgrowth. All included studies identified mechanisms potentially linking synovial fibroblasts to specific disease traits in juvenile idiopathic arthritis. Most findings were similar to mechanisms also described in synovial fibroblast from adults with arthritis. However, the limited number of studies found identifies an unmet need for additional studies on synovial fibroblasts and their potential role in juvenile idiopathic arthritis.

Disease characteristics of HLA-B27 positive and negative finnish patients with juvenile idiopathic arthritis - results of the 18-year cohort follow-up study.

BACKGROUND: The aim of this long-term follow-up study was to compare the disease characteristics of HLA-B27 positive and negative patients with juvenile idiopathic arthritis (JIA). METHODS: The study is a cohort study with consecutive cases of newly diagnosed Finnish patients with JIA according to the International League of Associations for Rheumatology (ILAR) criteria [1]. Patients were enrolled between 1997 and 2000 from a defined area of Southern Finland. Clinical data including disease activity and serology were registered during a mean period of 17.5 years. RESULTS: 159 patients completed the 18-year follow-up study. HLA-B27 was available for 151 patients, of which 25% were HLA-B27 positive. Chronic uveitis was diagnosed in 30% of HLA-B27 positive and 29% of HLA-B27 negative patients. HLA-B27 positive patients had a lower prevalence of temporomandibular (TMJ) involvement than the antigen negative ones, 19% versus 28%. None of the HLA-B27 positive patients had cervical spine affected compared to 11% of antigen negative patients (p = 0.022). Of the HLA-B27 positive patients, 54% had had biological medication at some point during follow-up versus 25% in the negative group (p = 0.003). At last follow-up, 32% of antigen positive patients were not in remission compared to 18% of the antigen negative (p = 0.017). CONCLUSIONS: The use of biological medication was more common in HLA-B27 positive patients with JIA. At the 18-year follow-up, more antigen positive patients had active disease compared HLA-B27 negative patients. This real-world follow-up study indicates that the prospects for worse outcome with HLA-B27 positivity in long-term should be taken into consideration.

Incidence of Orofacial Manifestations of Juvenile Idiopathic Arthritis From Diagnosis to Adult Care Transition: A Population-Based Cohort Study.

OBJECTIVE: To estimate the cumulative incidences of orofacial conditions related to temporomandibular joint (TMJ) juvenile idiopathic arthritis (JIA) between diagnosis in childhood to transition into adult care, and to identify features in JIA associated with TMJ involvement. METHODS: A population-based cohort analysis was conducted of patients with JIA involving longitudinal data on orofacial health from 2000 to 2018. Regardless of TMJ status, the patients were referred to the Regional Specialist Craniofacial Clinic of Western Denmark for routine orofacial examinations. Data collection included information about disease-specific background characteristics, TMJ involvement, JIA-induced dentofacial deformity, and orofacial symptoms and dysfunction. RESULTS: A total of 613 patients were followed up with a mean clinical TMJ observation time of 4.0 years. From JIA onset to transition into adult care, the cumulative incidence of patients with JIA involvement of the TMJ was 30.1%. Furthermore, 20.6% of the cohort had developed arthritis-induced dentofacial deformity. A substantial proportion of the cohort experienced several events with orofacial symptoms (23.5%) and dentofacial dysfunction (52%). Young age at diagnosis (<9 years), female gender, and antinuclear antibody positivity were significantly associated with TMJ involvement. CONCLUSION: Orofacial signs and symptoms were frequent findings in children and adolescents with JIA. TMJ involvement was seen in 30.1% of the cohort; and 20.6% of the total cohort developed JIA-related dentofacial deformity before transition into adult care. This is the first population-based study in the era of available biologic treatments to document these frequent orofacial complications in children with JIA.

A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings.

BACKGROUND: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings. METHODS: To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included. RESULTS: The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p < 0.001). CONCLUSIONS: Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.

Management of Orofacial Manifestations of Juvenile Idiopathic Arthritis: Interdisciplinary Consensus-Based Recommendations.

Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA.

[Biological therapy in juvenile idiopathic arthritis].

During the past 20 years of the biologic era, remission has become a realistic goal when treating children and adolescents with juvenile idiopathic arthritis (JIA). Studies describing long-term effects and safety are now available for several biologic agents, overall being well tolerated and with acceptable adverse events. No significant association between treatment with biologics and malignancy has been detected. This review finds that although biologics have been a success for most JIA patients, some fail to respond leaving the need for new treatment options and optimal switching between biologics most relevant.