Serum interleukin-18 levels can improve the diagnostic performance of the PRINTO and ILAR criteria for systemic juvenile idiopathic arthritis.

OBJECTIVE: Recently, the Pediatric Rheumatology International Trials Organization (PRINTO) has proposed revisions to the current International League of Associations for Rheumatology (ILAR) criteria for systemic juvenile idiopathic arthritis (s-JIA). Interleukin (IL)-18 overproduction plays a significant role in the pathogenesis of s-JIA. This study aimed to evaluate the performance of the PRINTO criteria compared with the ILAR criteria and determine whether serum IL-18 levels improve their diagnostic performances. METHODS: Overall, 90 patients with s-JIA and 27 patients with other febrile disease controls presenting with a prolonged fever of > 14 days and arthritis and/or erythematous rash were enrolled. The ILAR and PRINTO classification criteria were applied to all patients and examined with expert diagnoses. Enzyme-linked immunosorbent assay was used for measuring serum IL-18 levels. RESULTS: The PRINTO criteria had higher sensitivity but lower specificity than the ILAR criteria (sensitivity: PRINTO 0.856, ILAR 0.533; specificity: PRINTO 0.259, ILAR 0.851). With the addition of serum IL-18 levels ≥ 4,800 pg/mL, the sensitivity of the ILAR criteria and specificity of the PRINTO criteria were improved to 1.000 and 1.000, respectively. PRINTO plus serum IL-18 levels ≥ 4,800 pg/mL showed the highest value in Youden's index (sensitivity - [1 - specificity]). CONCLUSION: Serum IL-18 levels could improve the diagnostic performance of the PRINTO and ILAR criteria for s-JIA. The PRINTO criteria plus serum IL-18 levels ≥ 4,800 pg/mL could be the best diagnostic performance for s-JIA.

Evaluation of clinical outcomes in systemic juvenile idiopathic arthritis patients treated with biological agents in Turkey: the TURSIS study.

OBJECTIVES: Biological drugs are one of the most effective treatment methods for systemic juvenile idiopathic arthritis (SJIA) and can significantly prevent morbidity and mortality. This study aimed to evaluate the efficacy and safety of biologics in patients with SJIA and provide real-life data that might help improve the outcomes. METHODS: TURSIS was a retrospective multicentre study carried out in patients with SJIA for whom a biological treatment had been initiated between 1st March 2013 and 30th December 2018. Data include patients' characteristics, laboratory-clinical results, outcomes, and safety-related variables. The 24-month follow-up data of the patients and the efficacy and safety of biological drugs were evaluated. RESULTS: 147 patients were enrolled. The clinical course of the disease was as follows; it was monocyclic in 38.1%, polycyclic in 49%, and persistent in 12.9% of patients. First-choice biologics were interleukin (IL)-1 blockers in the majority of patients (56.5%), followed by the anti-IL-6 (25.2%) and anti-TNF-alpha drugs (18.4%). Anakinra was the most preferred biologic agent in patients with macrophage activation syndrome (MAS), and tocilizumab was used more frequently in patients with persistent type (p=0.000 and p=0.003). The most frequent switch rate was seen in patients receiving anakinra (n=40/68, 58.8%), and it was most frequently switched to canakinumab (n=32/40, 80%). Better physician's global assessment scores were achieved in patients treated with anakinra in Month 3, compared to other treatments (p=0.04). CONCLUSIONS: The results of our study support the efficacy of biological drugs in particular anti-IL-1 and anti-IL-6 drugs, in the treatment of SJIA. These treatments resulted in improvement in activity of disease and provide a considerable decrease in the frequency of MAS.

Clinical features, treatment and outcomes of Italian children with enthesitis-related arthritis and juvenile psoriatic arthritis: a cross-sectional cohort study.

OBJECTIVES: Limited information is available on the clinical features, treatment modalities and outcomes of the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA). This study was aimed to describe the characteristics of Italian children with ERA and JPsA and to compare them with those of patients with the other categories of JIA. METHODS: Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment approaches, and disease status in patients from across different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and laboratory tests, and recording of ongoing therapies. RESULTS: Of the 9081 children with JIA enrolled in the EPOCA Study, 1300 were recruited at 18 paediatric rheumatology centres in Italy. 45 (3.5%) had ERA and 49 (3.8%) had JPsA. Several remarkable differences in demographic features and frequency of articular and extra-articular manifestations, disease damage, impairment in physical function and health-related quality of life, school-related problems, comorbidities, and ongoing treatments were observed between ERA and JPsA and the other JIA categories. CONCLUSIONS: We described the characteristics of Italian children with ERA and JPsA and highlighted their peculiarities and their differences from the other JIA subsets. These data provide useful insights for future revisions of JIA classification and a benchmarking against which the features from other cohorts may be compared.

Prevalence of coeliac disease in patients with rheumatoid arthritis and juvenile idiopathic arthritis: a systematic review and meta-analysis.

OBJECTIVES: The reported prevalence of coeliac disease (CD) in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) varies in previous studies. We aimed to examine the prevalence of CD in patients with RA and JIA. METHODS: We searched Medline, Embase, Cochrane and Web of Science Core Collection between 1 January 1990 and 31 October 2022. In our primary analysis, the prevalence of biopsy-confirmed CD in RA and JIA patients was investigated. In secondary analyses, the prevalence of serological markers for CD was examined. Pooled weighted prevalences of CD and serological markers with 95% confidence intervals (95%CI) were calculated and quality of included studies was assessed. Meta-regression analysis was performed on publication year, sample size, CD prevalence in the general population, proportion of females, and quality assessment score. RESULTS: In this systematic review, 14 publications were deemed relevant for RA and 22 for JIA, with nine and 18 included in the primary analyses of CD prevalence, respectively. Among a total of 754 RA patients and 2077 patients with JIA, the weighted pooled prevalence estimates of biopsy-confirmed CD were 0.4% (95%CI=0.0-1.2) and 1.4% (95%CI=0.7-2.2), respectively. The pooled prevalence estimates of positive CD serology were 0.9% (95%CI=0.3-1.9) in RA and 5.4% (95%CI=2.5-9.2) in JIA. CONCLUSIONS: In this meta-analysis, we found a pooled prevalence of biopsy-confirmed CD in patients with RA and JIA comparable to that in the general population. Routine screening for CD is not warranted in RA but could be considered in JIA patients with additional risk factors for CD.

Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.

OBJECTIVES: TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. METHODS: In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. RESULTS: 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). CONCLUSIONS: Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.

The dual role of body mass index on Juvenile Idiopathic Arthritis course: a pediatric experience.

Despite the well-known role of obesity as risk factor for Juvenile Idiopathic Arthritis (JIA) severity, emerging but limited evidence suggested a similar role for underweight. We investigated the role of body mass index (BMI) across its full spectrum in a cohort of children with JIA.We retrospectively studied 113 children with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. The patients underwent a comprehensive evaluation including both clinical and biochemical assessments. According to BMI Z-score, the cohort was divided into five groups as underweight, normal weight, overweight (OW), obesity (OB), and severe OB. Disease activity was calculated by Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count and relapses were defined according to Wallace criteria.The mean age of the cohort was 7.43 ± 4.03 years. The prevalence of underweight, normal weight, OW, OB, and severe OB was 7.2%, 54.1%, 10.8%, 17.1%, and 10.8%, respectively. Significant higher ferritin levels and erythrocyte sedimentation rate values were found in patients with severe OB and underweight compared to subjects belonging to normal weight, OW, and OB groups. A greater JADAS-10 score was observed in underweight patients and in those with severe OB than other groups. The relapse rate was higher in patients with severe OB and underweight compared to other groups.          Conclusions: Both underweight and OB might negatively affect JIA course. Weight control is fundamental in children with JIA to avoid a more unfavourable course of the disease. What is Known: • Obesity represents a well-known risk factor for JIA severity. • The role of underweight in children with JIA is still poorly explored. What is New: • As observed in children with obesity, underweight young patients with JIA seem to experience a more severe JIA course. • Healthy lifestyle promotion in children with JIA is a crucial step in the management of the disease.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07-1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD. CONCLUSION: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. WHAT IS KNOWN: • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. WHAT IS NEW: • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Is tear proteome profile a predictor of developing uveitis in ANA-positive patients with oligoarticular juvenile idiopathic arthritis?

PURPOSE: Although less than one-third of anti-nuclear antibody (ANA) positive patients with oJIA develop uveitis, ANA positivity is still the most well-known marker for assessing the risk of uveitis in oligoarticular JIA (oJIA). Therefore, novel biomarkers are needed to better assess the risk of developing uveitis. For this purpose, we performed a comparative tear proteome analysis of uveitis patients to reveal the identity of differentially regulated proteins. DESIGN: Tear samples were collected using the Schirmer strips in 7 oJIA and 7 oJIA patients with uveitis (oJIA-U). All oJIA-U patients had developed bilateral anterior uveitis and were inactive and topical treatment-free. METHODS: The nHPLC LC-MS/MS system was used for protein identification and label-free proteome comparisons. The PANTHER and STRING analyses were carried out using UniProt accession numbers of the identified proteins. RESULTS: Patient characteristics, e.g., age, gender, disease duration, and treatments were similar. For protein identification, three different databases were searched. Twenty-two, 147, and 258 database searches, respectively. Of these, 15 were common to all three proteome databases. Of these 15 proteins, 10 proteins were upregulated, and 2 were downregulated, based on the twofold regulation criteria. The upregulated proteins were, namely, cystatin-S, secretoglobin family 1D member, opiorphin prepropeptide, mammaglobin-B, lysozyme C, mesothelin, immunoglobulin kappa constant, extracellular glycoprotein lacritin, beta-2-microglobulin, and immunoglobulin J chain. The downregulated proteins were dermcidin and prolactin-inducible protein. Among the differentially regulated proteins, cystatin-S was the most regulated protein with an 18-fold upregulation ratio in tear samples from uveitis patients. CONCLUSION: Here, the identities and regulation ratios of several proteins were revealed when tear samples from uveitis patients were compared to patients without uveitis. These proteins are putative biomarkers for assessing uveitis risk and require further attention.

Frosted branch angiitis in a patient with systemic juvenile idiopathic arthritis: a case report.

BACKGROUND: Frosted branch angiitis is a retinal vascular condition that is associated with a viral infection or autoimmune disorders like Crohn's disease, systemic lupus erythematosus, and Behcet's disease. Frosted branch angiitis presents with vascular inflammation, retinal edema, and severe retinal vascular sheathing. We present a case of systemic juvenile idiopathic arthritis, an autoinflammatory disease, presenting with frosted branch angiitis. REPORT OF CASE: A 14-year-old female with systemic juvenile idiopathic arthritis and a history of bilateral anterior uveitis developed acute unilateral vision loss and was found to have frosted branch angiitis complicated by branch retinal vein occlusion. She underwent an extensive serology workup and aqueous viral PCR to rule out other possible autoimmune and viral etiologies for forested branch angiitis. She received systemic and intravitreal antiviral treatment due to positive CMV IgM initially. However, the clinical picture improved following the use of a higher dose of oral steroids and the switch of the immunosuppressive agent to a TNF-a inhibitor. CONCLUSION: To our knowledge, this would be the first case in the literature demonstrating a systemic juvenile idiopathic arthritis patient presenting with frosted branch angiitis. Infectious causes still must be ruled out, especially CMV, as it is the most common cause of secondary frosted branch angiitis.

A MASsive attack: a pediatric case of macrophage activation syndrome complicated by DIC as an onset of systemic juvenile idiopathic arthritis successfully treated with anakinra and review of the literature.

Macrophage activation syndrome (MAS) is one of the most severe complications of systemic juvenile idiopathic arthritis (sJIA). Around 10% of patients with sJIA exhibit systemic symptoms accompanied by macrophage activation syndrome (MAS), but it may occur subclinically in another 30-40%. In this article, we present a case of a 3-year-old girl diagnosed with sever MAS as an onset of sJIA complicated by disseminated intravascular coagulation (DIC). First symptoms of sJIA were observed about 5 months before setting the diagnose, and it was resembling urticaria. A comprehensive allergological diagnostics were conducted, but no cause for the skin changes was identified. A few weeks before admission to the hospital, the girl was presented with a high fever. During the hospital stay, viral, bacterial, and fungal infections were ruled out. However, the findings indicated significantly elevated markers of inflammation (ferritin, CRP, ESR) in the conducted tests. Meanwhile, swelling of the feet and ankle joints was also observed. Based on Ravelli criteria, we set the diagnosis of MAS in a course of sJIA. We implemented treatment with steroid pulses, followed by cyclosporine; however, her clinical condition did not improve. Despite intensive treatment, skin petechiae were observed twice, and laboratory tests revealed a very high INR along with an extremely low level of fibrinogen. The patient required multiple plasma transfusions and clotting factor administrations. Due to the severe condition of the girl, we initiated biological treatment with anakinra, after which the child's condition gradually improved. In this case, we want to present how dynamic and life-threatening the course of MAS can be. In the discussion, we are also comparing our approach and the applied treatment with the currently available knowledge.

Criteria for Cytokine Storm Syndromes.

In the past two decades, there has been a great deal of work aimed to devise diagnostic guidelines, classification criteria, and diagnostic scores for cytokine storm syndromes (CSSs). The most notable effort has been the large-scale multinational study that led to the development of the 2016 classification criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). Future studies should scrutinize the validity of the proposed criteria, particularly in systemic JIA patients treated with biologics, in children with subtle or incomplete forms of MAS, and in patients with MAS complicating other rheumatologic disorders. More generic CSS criteria are also available but often lack sensitivity and specificity in a wide variety of patient populations and CSSs of different etiologies. The coronavirus disease 2019 (COVID-19)-related lung disease led to an evolution of the concept of a "cytokine storm." Emerging and unsolved challenges in the diagnosis of the different forms of CSSs highlight the need for diagnostic tools and well-established classification criteria to enable timely recognition and correct classification of patients.

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response.

BACKGROUND: Determining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets. AIM: We aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA. MATERIALS AND METHODS: This cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children's Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann-Whitney, Kruskal-Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination. RESULTS: Forty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve. CONCLUSION: The significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination.

Prevalence of temporomandibular disorders in juvenile idiopathic arthritis evaluated with diagnostic criteria for temporomandibular disorders: A systematic review with meta-analysis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a very common systemic inflammatory rheumatic disorder affecting the musculoskeletal system in children below 16 years of age. Joint inflammation and tissue destruction is the prime characteristic of the disease. Along with the systemic involvement in the long joints, several studies are mentioning the increased association of temporomandibular disorders (TMDs) in JIA. This current systematic review intends to find the prevalence rate of TMD in JIA-affected individuals as compared to healthy controls. METHODS: We have searched in PubMed, Scopus and Ovid SP for articles published between the timeframe 1 January 1990 and 1 June 2023. All the searched articles were subjected to the Population, Exposure, Comparison, and Outcome model (PECO) based on which inclusion or exclusion is carried out. Participants (P) are children below 18 years of age, Exposure (E) is children or adolescents with a diagnosis of JIA, Comparator is age and gender-matched healthy controls who has no JIA or any systemic disorder, Outcome (O) is the prevalence of TMD. Only the studies that evaluated TMD using diagnostic criteria for evaluation of TMD (DC/TMD) were included in the analysis. We have set the exclusion to the following reasons- diagnostic sensitivity studies, case reports, and systematic reviews. The software Review Manager Version 5.4 (Cochrane Collaboration) was used to perform the pooled analysis. We measured the risk ratio (RR) between the two groups (JIA and no JIA) for the outcome TMD. RESULTS: The pooled total included subjects were 366 in this review with an established diagnosis of JIA as evaluated by DC/TMD. The overall effect of the pooled data suggests that there is a significant difference in the TMD prevalence in the JIA group when compared to the control, results suggest that TMD is more prevalent in the JIA group RR 3.86; 95% CI [2.59, 5.76]. CONCLUSION: Overall, based on the data we can suggest a positive relationship between JIA and TMD, hence presence of JIA can be a risk factor for the development of TMD. The sensitivity of DC/TMD is low when compared to magnetic resonance imaging.

Is There a Link between the Molecular Basis of Juvenile Idiopathic Arthritis and Autoimmune Diseases? Systematic Review.

Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up. METHODS: We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases. RESULTS: A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed. CONCLUSIONS: Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.

[Monogenic variants in Laccase domain-containing 1 (LACC1) as the cause of juvenile arthritis]. / Monogene Varianten in "laccase domain-containing 1" (LACC1) als Ursache einer juvenilen Arthritis.

Monogenic mutations in laccase domain-containing 1 (LACC1) are associated with clinical pictures that mimic severe courses of polyarticular or systemic juvenile idiopathic arthritis. The diseases are characterized by an early onset during the first year of life, a familial clustering and a high inflammatory activity. The courses are mostly difficult to influence and often lead to sequelae. In this article four cases from two families are presented in which the homozygous mutation p.T276fs* in LACC1 was detected. The children initially suffered from polyarticular or systemic forms of juvenile arthritis. Of the patients two are currently being treated with tocilizumab and methotrexate and one female patient without a basis treatment is currently only receiving local repeated intra-articular steroids. A fourth female patient underwent an allogeneic bone marrow transplantation due to a relapse of an acute lymphatic leukemia. Since then, no further inflammatory symptoms have occurred. The cases presented are compared with the other 50 courses published to date. In addition, recent studies investigating the influence of LACC1 mutations, particularly on macrophage function, are summarized.

[Protocols in pediatric rheumatology (PROKIND): treat-to-target in polyarticular juvenile idiopathic arthritis]. / Protokolle in der Kinderrheumatologie (PROKIND): Treat-to-Target bei polyartikulärer juveniler idiopathischer Arthritis.

BACKGROUND: The aims of the PROKIND protocols are improvement and harmonization of the diagnostics, monitoring, treatment decision and prognosis. MATERIAL AND METHODS: This article reports the results of a prospective treat-to-target observational study of patients with polyarticular juvenile idiopathic arthritis (JIA) during the first year of treatment. Disease activity was assessed with the 10-joint juvenile arthritis disease activity score (JADAS-10), functional limitation with the childhood health assessment questionnaire disability index (CHAQ-DI) and with information on overall well-being, on pain, on fatigue and on global estimation of disease activity. RESULTS: Overall, 129 patients with polyarticular JIA (rheumatoid factor, RF, positive (+) polyarthritis n = 22, RF negative (-) polyarthritis n = 133 from 23 pediatric rheumatology institutions in Germany and Austria were recruited. Patients with initial treatment with methotrexate formed cohort 1, patients with additional repeated intravenous corticosteroid pulse therapy formed cohort 2 and patients with concomitant intra-articular corticosteroid administration in at least 5 joints formed cohort 3. The mean JADAS10 showed a decrease in disease activity from 16.4 ± 6.1 to 2.8 ± 3.6 and the decrease in the CHAQ-DI from 1.0 ± 0.8 to 0.3 ± 0.5 showed the improvement in functional capacity. Similarly, improvements in quality of life, pain and fatigue were demonstrable. A JADAS inactive disease was achieved by 18.1% at month 3, 47.7% at month 6 and 66.7% at month 12. In cohort 1 a JADAS remission was achieved by 72.4%, by 50% in cohort 2 and by 69.2% in cohort 3. An escalation to treatment with biologics was necessary in 38% of patients in cohort 1, 60% in cohort 2 and 46% in cohort 3. CONCLUSION: Using a treat-to-target approach a dramatic improvement in disease activity, functional capacity and quality of life in polyarticular JIA could be achieved. Even after 12 months an inactive disease was achieved in the majority of cases.

Disease activity assessment for juvenile idiopathic arthritis in transitional care.

OBJECTIVE: The indices to measure disease activity of chronic arthritis in adulthood and childhood are different. Therefore, assessing the status of the disease in young patients with juvenile idiopathic arthritis (JIA) can be tricky, especially when the transition to adult care is ongoing. The aim of our study was to assess the level of correlation between adult and juvenile scores in the measurement of disease activity in JIA patients during transitional care. METHODS: We estimated the disease activity by using the Juvenile Arthritis Disease Activity Score 71 (JADAS71), clinical JADAS, adult Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in JIA patients in transitional care. We enrolled patients older than 16 years at the time of the first transition visit, and disease activity was assessed at baseline and 12 months. Regression analyses were carried out to estimate the level of agreement among the different indices. RESULTS: We recruited 26 patients with JIA; 11 patients were polyarticular (42.3%) and 15 patients were oligoarticular (53.1%). The mean age at diagnosis was 7.7±3.9 years and the age at the first evaluation was 20.9±3.7 years. The correlation between JADAS71 and DAS28 was r2=0.69, r2=0.86 between JADAS71 and SDAI, and r2=0.81 between JADAS71 and CDAI. CONCLUSIONS: SDAI and JADAS71 showed the best correlation, but a few patients were not captured at the same level of disease activity. New prospective studies with a larger number of patients will be needed in this field.

New developments related to lung complications in pediatric rheumatic disease.

PURPOSE OF REVIEW: While substantial progress has been made understanding lung disease in adult patients with rheumatic disease, pediatric lung disease has not been well addressed. Several recent studies provide new insights into diagnosis, management and treatment of lung disease in children with rheumatic disease. RECENT FINDINGS: Building on previous research, newly diagnosed patients may have abnormalities in pulmonary function tests and chest computed tomography imaging even when asymptomatic. New guidelines for screening for rheumatic-associated lung disease provide important recommendations for clinicians. New theories have been proposed about immunologic shifts leading to the development of lung disease in children with systemic juvenile idiopathic arthritis. Additionally, there are new antifibrotic agents that are being explored as treatments in pediatric patients with fibrotic lung diseases. SUMMARY: Patients appear to have frequent lung function abnormalities while being clinically asymptomatic, emphasizing importance for rheumatologists to refer for pulmonary function tests and imaging at diagnosis. New advances are helping define optimal approaches to treatment of lung disease, including use of biologic agents and antifibrotic medicines for pediatric patients with rheumatologic diseases.

Improvement of Refractory Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease with Single-Agent Blockade of IL-1ß and IL-18.

Systemic juvenile idiopathic arthritis associated with interstitial lung disease (SJIA-LD) represents a highly morbid subset of SJIA for which effective therapies are lacking. We report the case of a patient with refractory SJIA-LD who underwent treatment with MAS-825, an investigational bispecific monoclonal antibody targeting IL-1ß and IL-18. MAS-825 treatment was associated with a marked reduction in total IL-18 and free IL-18 in both serum and bronchoalveolar lavage fluid (BAL). Baseline oxygen saturation, exercise tolerance, and quality of life metrics improved after treatment with MAS-825, while pulmonary function testing remained stable. Following treatment, the BAL showed no evidence of pulmonary alveolar proteinosis and inflammatory infiltrates were markedly reduced, reflected by decreased numbers of CD4 T-cells, CD8 T-cells, and macrophages. The patient was able to wean entirely off systemic corticosteroids and other biologics after 10 months of treatment with MAS-825 and experienced no side effects of the drug. This case demonstrates improvement in pulmonary symptoms, lung inflammation, and burden of immunomodulatory therapy after treatment with MAS-825 and suggests that simultaneous targeting of both IL-1ß and IL-18 may be a safe and effective treatment strategy in SJIA-LD.

Efficacy and safety of emapalumab in macrophage activation syndrome.

OBJECTIVES: Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-γ (IFNγ) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria. METHODS: We studied emapalumab, a human anti-IFNγ antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study. RESULTS: Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFNγ activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed. CONCLUSIONS: Neutralisation of IFNγ with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus. TRIAL REGISTRATION NUMBER: NCT02069899 and NCT03311854.