Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Risk factors associated with multiple organ damage in childhood-onset systemic lupus erythematosus.

Objective: Previous studies have shown that approximately 39%-65% of patients with childhood-onset systemic lupus erythematosus (cSLE) have damage in at least one organ. Data on risk factors for organ damage in cSLE remain limited, especially in Asian populations. This study was conducted to evaluate the incidence of cSLE and identify the risk factors for accumulated organ damage in patients with cSLE. Methods: This was a retrospective study. Patients aged <18 years who were diagnosed with cSLE between 2008 and 2020 were enrolled. Information on baseline characteristics, treatment, and disease activity assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was collected from diagnosis until the most recent visits were reviewed from medical records. Disease damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Results: A total of 134 patients with a mean age at diagnosis of 11.2 ± 2.9 years were enrolled. The median duration of treatment was 4.7 (interquartile range 2.8-7.1) years. Forty patients (29.9%) had irreversible organ damage (SDI > 1) with an incidence rate of 5.7 events per 100 person-years. The most frequent type of organ damage was ocular (11.1%), followed by musculoskeletal (8.9%) and neurological (7.4%). High disease activity at diagnosis (SLEDAI-2K ≥ 12) (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.32-7.68), infection (OR 3.73, 95% CI 1.60-8.67), and mycophenolate mofetil use (OR 3.62, 95% CI 1.45-9.03) were predictors of organ damage. The median time to disease damage in patients with SLEDAI-2K scores ≥12 at diagnosis was 6.5 years (95% CI 5.77-7.36; P = 0.004). Conclusion: Physicians should be aware of organ damage in patients with cSLE, particularly those with high disease activity at initial presentation, those who are receiving mycophenolate mofetil therapy, and those with an infection.

Outcomes in children with rheumatic diseases following COVID-19 vaccination and infection: data from a large two-center cohort study in Thailand.

Introduction: Vaccination against coronavirus disease 2019 (COVID-19) is effective in protecting patients from severe COVID-19 infection. Disease flare-up following immunization in children with rheumatic disorders may result in patient reluctance to receive the vaccine. Underlying rheumatic diseases or the use of immunosuppressive drugs may influence the outcomes of COVID-19 vaccination and infection. We aimed to describe outcomes in children with rheumatic diseases following COVID-19 immunization and infection. Methods: This retrospective study was performed at two large academic centers in Thailand. During the COVID-19 pandemic, all patients were routinely queried about COVID-19-related conditions. We included patients with rheumatic diseases aged <18 years who received at least one dose of a COVID-19 vaccine or had a history of COVID-19 infection with more than 6 months of recorded follow-up after the last vaccine dose or COVID-19 illness. Demographic information and data on clinical symptoms, disease activity, treatment, outcomes, and COVID-19 vaccination and infection were collected. Results: A total of 479 patients were included. Most (229; 47.81%) patients had juvenile idiopathic arthritis, followed by connective tissue diseases (189; 39.46%), vasculitis syndromes (42; 8.76%), and other rheumatic diseases (19; 3.97%). Approximately 90% of patients received at least one dose of COVID-19 vaccination, and half of the patients had COVID-19 infection. Among patients, 10.72% and 3.27% developed a flare after COVID-19 vaccination and COVID-19 illness, respectively. Flare severity after COVID immunization and infection was mainly mild to moderate. The predictor of flare after COVID-19 vaccination was the use of prednisolone ≥10 mg/day before vaccination (hazard ratio: 2.04, 95% confidence interval: 1.05-3.97, p = 0.037). Inactive disease before receiving the COVID-19 vaccination was a predictor of inactive status after a flare (hazard ratio: 2.95, 95% confidence interval: 1.04-8.40; p = 0.043). Overall, 3.36% and 1.61% of patients experienced a new onset of rheumatic disease after receiving the COVID-19 vaccine and after COVID-19 infection, respectively. Conclusion: The COVID-19 vaccine is recommended for children with rheumatic disease, particularly those who are in stable condition. After COVID-19 vaccination, patients-especially those with active disease before vaccination or those receiving concurrent prednisolone doses of ≥10 mg/day-should be closely monitored.

Factors associated with medication adherence among children with rheumatic diseases.

Introduction: Failure to take medications regularly leads to poorer health outcomes. The Pediatric Rheumatology Adherence Questionnaire (PRAQ) is an effective tool for assessing medication adherence in rheumatic patients. Therefore, we aimed to determine the factors associated with poor medication adherence among children with rheumatic diseases. Methods: This was a cross-sectional study. Patients with rheumatic diseases who had taken at least one medication and had been followed up at our pediatric rheumatology clinic were included in the study, together with their caregivers. Patients with poor medication adherence were characterized as those who had taken less than 80% of their prescribed drugs, as determined using the pill count method. The original PRAQ was translated and validated in Thai language and was completed by caregivers and literate patients over age 13 years. Interviewing for additional problems with taking medications was conducted. We performed descriptive and logistic regression analyses. Results: From 210 patients, 52.86% had juvenile idiopathic arthritis (JIA), and 46.19% had connective tissue diseases. The mean patient age was 14.10 ± 4.74 years, with a median (interquartile range) disease duration of 4.33 (2.08-6.98) years. PRAQ scores in the group with poor adherence were significantly higher than scores in the group with good adherence (11.00 ± 3.47 vs. 9.51 ± 3.16, p = 0.004). Enthesitis-related arthritis (ERA) (odds ratio [OR] 9.09, 95% confidence interval [CI] 1.25-66.18; p = 0.029) and polyarticular JIA (OR 6.43, 95% CI 1.30-31.75; p = 0.022) were associated with poor treatment adherence. Disease duration ≥5 years (OR 3.88, 95% CI 1.17-12.87; p = 0.027), active disease (OR 6.49, 95% CI 1.76-23.99; p = 0.005), PRAQ scores ≥12 (OR 6.48, 95% CI 1.76-23.82; p = 0.005), forgetting to take medications (OR 14.18, 95% CI 4.21-47.73; p < 0.001), and unawareness about the importance of the medicines (OR 44.18, 95% CI 11.30-172.73; p < 0.001) were predictors of poor drug adherence. Conclusion: In the present study, poor medication adherence was found in one-fourth of children with rheumatic illnesses, particularly those with ERA, polyarticular JIA, longer disease duration, active disease, and high PRAQ scores. The most frequent reasons for inadequate medication adherence were forgetfulness and unawareness about the importance of disease control and consistency with treatment.

Central nervous system involvement and thrombocytopenia as predictors of mortality in children with hemophagocytic lymphohistiocytosis.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition. This study aimed to evaluate treatment outcomes and identify prognostic-related factors in Thai children with HLH. Materials and methods: We retrospectively reviewed the medical records of 76 pediatric patients with HLH who were treated at Ramathibodi Hospital between January 2004 and December 2019. Treatment outcomes were defined as early mortality (death within 30 days after diagnosis) and early treatment response (resolution of all clinical features and normalization of at least one HLH-related laboratory parameter within 4 weeks). Results: The overall mortality rate was 38% (29/76), with an early mortality rate of 45% (13/29). Malignancy-associated HLH had the highest mortality rate (88%), followed by primary HLH (56%). The predictors of early mortality were central nervous system (CNS) involvement [OR 13 (95%CI 2-83), p = 0.007] and platelet counts <44 × 106/mm3 [OR 8 (95%CI 1.3-49), p = 0.024]. The predictors of early treatment response were no CNS involvement [OR 6.6 (95%CI 1.5-28.8), p = 0.011], platelet counts more than 44 × 106/mm3 [OR 8 (95%CI 2.1-30.9), p = 0.003], and total bilirubin levels <1.8 mg/dL [OR 4 (95%CI 1.1-14.8), p = 0.036]. In the mixed-model analysis, platelet counts in non-survivors increased significantly less than those in survivors, with a mean difference in platelet changes between the two groups of 94.6 × 106/mm3 (p = 0.003). Conclusion: The independent predictors of early mortality in children with HLH were CNS involvement and low baseline platelet counts. A slow rate of platelet increases during the first week after diagnosis was also associated with mortality.

Comparison of the outcomes between early and late anti-tumor necrosis factor therapy in patients with enthesitis-related subcategory of juvenile idiopathic arthritis: a multi-center study in Southeast Asia.

BACKGROUND: Little is known about the impact of delayed initiation of anti-tumor necrosis factor (TNF) therapy in patients with enthesitis-related arthritis (ERA). Here, we compared the impact of delayed treatment on disease outcomes of ERA patients in Southeast Asia. RESEARCH DESIGN AND METHODS: This retrospective study enrolled 149 ERA patients from Thailand and Singapore. Early (e-aTNF) and late (l-aTNF) treatment groups received anti-TNF therapy starting at ≤6 months and >6 months, respectively, after diagnosis. Outcomes included mean differences in disease activity parameters, Juvenile Spondyloarthritis Disease Activity (JSpADA) score, Juvenile Arthritis Diseases Activity (JADAS)-10 score, and American College of Rheumatology Pediatric (ACR Pedi) criteria, and the frequency of clinically inactive disease and first flare event. RESULTS: The mean changes in JSpADA (p = 0.002) and JADAS-10 (p < 0.001) scores over time were significantly higher in the e-aTNF group than in the l-aTNF group. A significantly higher proportion of patients in the e-aTNF group than l-aTNF group satisfied ACR Pedi 100 criteria at 2 years (p = 0.042). All other long-term outcomes were not significantly different between the groups. CONCLUSIONS: Although early anti-TNF treatment improved disease activity parameters somewhat better than delayed anti-TNF therapy, there was no significant difference in long-term outcomes.

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus.

OBJECTIVE: Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. METHODS: A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. RESULTS: The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. CONCLUSION: JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes.

Long-term growth and final adult height outcome in childhood-onset systemic lupus erythematosus.

BACKGROUND: Growth impairment is the most common complication in patients with childhood-onset systemic lupus erythematosus (cSLE). There are limited data on risk factors affecting growth development in Asian patients with cSLE. This study aimed to determine the predictors of growth impairment in such patients. METHODS: All SLE patients aged < 15 years diagnosed in Ramathibodi Hospital between 2006 and 2016 were enrolled in a retrospective cohort study. Baseline characteristics, including height, weight, clinical manifestations, disease activity score, and medications, were reviewed from medical records from the time at diagnosis to achievement of final adult height (FAH). Age at menarche in girls, adult voice appearance in boys, and parental height were collected by interview. Parent-adjusted FAH (PaFAH) Z-score was calculated as the difference between FAH Z-score for chronological age of the patients and their mid parental height-Z score. The patients were classified into two groups: (1) normal growth (PaFAH Z-score ≥ - 1.5, 2) growth impairment (PaFAH Z-score < - 1.5). Descriptive statistics and logistic regression analysis were used to analyze the data. RESULTS: Of 106 cSLE patients, 19 (18%) were male and 87 (82%) were female. The mean age at study enrollment was 20.6 ± 3.0 years, mean age at diagnosis 12.1 ± 2.3 years, and mean age at achievement of FAH 17.5 ± 1.9 years. Growth impairment was found in 23.6% of patients (52.6% in boys and 17.2% in girls). Predictors of growth impairment were male sex, duration of disease before menarche in girls and adult voice appearance in boys, and cumulative corticosteroid dose (prednisolone equivalent) ≥230 mg/kg received before the late phase of puberty, with odds ratios of 7.07 (95%CI 2.11-23.74), 1.26 (95% CI 1.02-1.56), and 6.99 (95%CI 1.63-30.02), respectively. CONCLUSIONS: One-fourth of cSLE patients developed growth impairment, which mostly affected male patients. Longer duration of disease before the late phase of puberty and corticosteroid dose ≥230 mg/kg received before the late phase of puberty were factors predictive of growth impairment.

Evaluating performance of the 2019 EULAR/ACR, 2012 SLICC, and 1997 ACR criteria for classifying adult-onset and childhood-onset systemic lupus erythematosus: A systematic review and meta-analysis.

Introduction: The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE criteria are often used to classify patients with adult-onset and childhood-onset systemic lupus erythematosus (SLE) in clinical practice because there are currently no diagnostic criteria for SLE. However, there is scarce evidence regarding which criteria are best for diagnosing patients with adult-onset and childhood-onset SLE. Methods: We searched Medline and Scopus databases for English-language articles from inception through October 2021. Data were extracted from the included publications by two independent reviewers. We performed bivariate meta-analysis with a random-effects model to pool diagnostic parameters. Meta-regression and subgroup analyses were performed to explore heterogeneity sources. We used network meta-analysis to compare diagnosis performance among the three criteria and ranked them in descending order. Publication bias was assessed using Deeks' funnel plot. Results: We included 29 studies for systematic review and meta-analysis. Of these, 18 studies involved adult-onset SLE and 11 studies involved childhood-onset SLE. The pooled sensitivities of the three criteria for diagnosis of adult-onset SLE were comparable between SLICC 2012 and EULAR/ACR 2019 [95.86, 95% confidence interval (CI) 92.28-97.81 vs. 94.79, 95% CI 92.03-96.63]; pooled specificity was highest in ACR 1997 (92.24, 95% CI 87.06-95.46). In childhood-onset SLE, pooled sensitivity was highest in SLICC 2012 (93.76, 95% CI 89.45-96.39), and pooled specificity was highest in ACR 1997 (95.89, 95% CI 91.73-98.00). In network meta-analysis, the pooled diagnostic odds ratio ranked highest for EULAR/ACR 2019 (131.570, 95% CI 61.50-281.47) in adult-onset SLE and ranked highest for SLICC 2012 (191.07, 95% CI 76.06-480.01) in childhood-onset SLE. Deeks' funnel plot showed no publication bias. Conclusion: We found that the diagnostic performance of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria differed between adult-onset and childhood-onset SLE. EULAR/ACR 2019 performed best for adult-onset SLE and SLICC 2012 was best for childhood-onset SLE in classifying patients with SLE. Systematic review registration: [www.ClinicalTrials.gov], identifier [CRD420 21281586].

Associations between HLA-B27 subtypes and outcomes in Thai children with enthesitis-related arthritis.

OBJECTIVE: Expression of human leukocyte antigen B27 (HLA-B27) has been identified as a predictor of severe disease in enthesitis-related arthritis (ERA) patients. However, the associations between HLA-B27 subtypes and outcomes of this disease are still unclear. Here, we examined the distributions of HLA-B27 subtypes among ERA patients and the associations with disease outcomes. METHODS: This was a historical cohort study of ERA patients. Patients were followed from diagnosis to the most recent visit. Relationships between outcomes and the HLA-B27 subtype were assessed by mixed-effect regression, Kaplan-Meier survival, and Cox proportional hazards regression analyses. RESULTS: Of the 66 ERA patients, 50 HLA-B27-positive (86% male) and 16 HLA-B27-negative (69% male) patients were included in this study. Patients with HLA-B27-positive were classified into HLA-B*27:04-positive (84%), including combined HLA-B*27:04 and HLA-B*27:07 (2%), and HLA-B*27:04-negative (16%), including HLA-B*27:05 (10%), HLA-B*27:06 (2%), HLA-B*27:07 (2%), and HLA-B*27:15 (2%). HLA-B*27:04-positive (83.3%) and HLA-B*27:04-negative patients (100%) had refractory disease more than HLA-B27-negative patients (37.5%, p = 0.001). HLA-B*27:04-negative patients (57%, 1.73 years) had relapsing disease more and earlier than HLA-B*27:04-positive (35%, 5.54 years) and HLA-B27-negative patients (40%, 6.92 years; p < 0.001). Furthermore, HLA-B*27:04-negative was predictors of refractory disease (HR 4.56, 95%CI 1.40-14.87; p = 0.012) and relapsing disease (HR 3.80, 95% CI 1.18-12.30; p = 0.026). The duration before anti-tumor necrosis factor treatment initiation > 1 year was also a predictor of refractory disease (HR 116.08, 95% CI 14.67-918.26; p < 0.001). CONCLUSION: HLA-B*27:04 was the most common HLA-B27 subtype in Thai ERA patients. HLA-B*27:04-negative was associated with more unfavorable outcomes than HLA-B*27:04-positive and HLA-B27-negative patients. Key Points • Most ERA patients in Thailand had HLA-B27-positive, and HLA-B*27:04 was the most common HLA-B27 allele in these patients. • The outcomes of ERA were associated with the presence of HLA-B27 and its subtypes. • HLA-B*27:04-negative patients had unfavorable outcomes, including refractory and relapsing disease, compared to HLA-B*27:04-positive and HLA-B27-negative patients.

Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response.

OBJECTIVE: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. METHODS: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. RESULTS: Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (rs = 0.81, P < 0.0001) and galectin-9 (rs = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). CONCLUSION: Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential.

Assessment of transition readiness in adolescents in Thailand with rheumatic diseases: a cross-sectional study.

BACKGROUND: Most childhood-onset rheumatic diseases are chronic health conditions, which need long-term care throughout adulthood. A well-organized transition care is challenging and patient assessment of transition skills is needed for transfer preparation to an adult care setting. The Transition Readiness Assessment Questionnaire (TRAQ) is used to assess transition skills in chronically ill patients. Currently, limited transition skill assessment data exist in pediatric patients with rheumatic diseases, especially in Asian countries. This study aimed to determine the transition readiness skills in patients with rheumatic diseases and ascertain predictive factors contributing to high transition readiness skills. METHODS: This is a cross-sectional study. All patients with rheumatic diseases aged 15-20 years were recruited. The TRAQ was cross-culturally adapted into the Thai language with good internal consistency and reliability. Patients completed the Thai TRAQ at the recent clinic visit and took the retest at a 2-week interval. Demographic data, baseline characteristics, clinical manifestations, and disease status were collected. Descriptive and logistic regression analyses were performed. RESULTS: A total of 111 patients with a mean age of 17.4 ± 1.8 years were included. Median (IQR) disease duration was 6.4 (3.2-9.0) years. The most common rheumatic disease was juvenile idiopathic arthritis (48.6%), followed by systemic lupus erythematosus (35.1%). The mean TRAQ score was 3.85 ± 0.69. Independent visits (OR 4.35, 95% CI 1.23-15.37) was a predictor of a high TRAQ score. Furthermore, dependent visits (OR 7.84, 95% CI 2.41-25.50) was a predictor of low TRAQ score in the "appointment keeping" domain, whereas inactive disease (OR 4.54, 95% CI 1.25-16.55) was a predictor of a low TRAQ score in "tracking health issues" domain. Lack of knowledge and skills on health insurance coverage, financial management, appointment arrangement, and coping with their illness were issues causing lower TRAQ score. CONCLUSIONS: Patients, who had independent visits, had a higher chance to obtain higher TRAQ scores, whereas patients, who had an inactive disease or dependent visits, had less transition readiness skills. Physicians and parents should prepare to transfer patients to adult care settings, mainly encouraging independent living skills.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

Age-related changes in lymphocyte subpopulations in healthy Thai children.

BACKGROUND: Ethnicity and environmental factors can influence the percentages of lymphocyte subpopulations. This study aimed to assess the percentages of lymphocyte subpopulations according to age in Thai children. METHODS: This was a cross-sectional study. The percentages of lymphocyte subpopulations were measured in umbilical cord blood and peripheral blood of healthy Thai children aged 1 month-15 years. The participants were stratified into five age groups: (a) cord blood; (b) age < 2 years; (c) age 2-5 years; (d) age 5-10 years; and (e) age 10-15 years. RESULTS: Of 182 total samples, 32, 39, 41, 28, and 42 were from cord blood, children aged <2 years, children aged 2-5 years, children aged 5-10 years, and children aged 10-15 years, respectively. The percentages of most lymphocyte subpopulations including CD8 + T cells, CD19 + cells, γδ T cells, double-negative T cells, NK cells, and NK T cells increased significantly with age. Only the CD4+ T-cell percentage decreased in older children. Moderate correlations were observed between age and the percentages of CD4+ T cells, γδ T cells, NK cells, NK T cells, and double-negative T cells. Weak correlations were observed between age and the percentages of CD8+ T cells and CD19+ cells. CONCLUSION: Our study demonstrated age-related changes in the percentages of lymphocyte subpopulations in Thai children, which differed from those described in other countries. Therefore, the establishment of age-specific reference values for lymphocyte subsets in each country is recommended.

Correlations between serum interleukin 6, serum soluble interleukin 6 receptor, and disease activity in systemic juvenile idiopathic arthritis patients treated with or without tocilizumab.

INTRODUCTION: Interleukin (IL)-6 is a proinflammatory cytokine involved in systemic juvenile idiopathic arthritis (SJIA). Since these patients are often treated with tocilizumab (TCZ), anti-IL-6 receptor (IL-6R) antibody, we investigated correlations between serum IL-6 and soluble IL-6R-levels and disease activity in SJIA patients treated with or without TCZ. MATERIAL AND METHODS: 164 serum samples were taken from 42 SJIA patients treated with or without TCZ (69 and 95 samples, respectively). Patients were assigned to three groups according to disease status: 1) systemic (patients with systemic features and/or arthritis), 2) arthritis (patients with arthritis but no systemic features), and 3) inactive (clinically inactive disease). Disease activity was assessed using the Juvenile Arthritis Disease Activity Score-27 (JADAS-27) at the time of blood collection. RESULTS: IL-6 levels were highest in SJIA patients with predominant systemic features, while serum sIL-6R levels were highest in patients with persistent arthritis. Serum IL-6 correlated with JADAS-27 in patients treated with and without TCZ (r = 0.38 and r = 0.65, respectively), whereas serum sIL-6R levels correlated with JADAS-27 in patients treated without (r = 0.30) but not with (r = -0.14) TCZ. The sIL-6R/IL-6 ratio negatively correlated with JADAS-27 in patients treated with and without TCZ (r = -0.49 and r = -0.56, respectively). CONCLUSIONS: Serum IL-6 levels correlated more strongly with disease activity parameters than did sIL-6R levels and could be useful for monitoring disease activity in SJIA patients. The sIL-6R/IL-6 ratio might be a promising disease activity marker in both SJIA patients treated with and without TCZ.

Recurrent ruptured abdominal aneurysms in polyarteritis nodosa successfully treated with infliximab.

Systemic polyarteritis nodosa (PAN) is a rare form of necrotizing vasculitis in children. Recurrent episodes of abdominal aneurysm ruptures are uncommon and life-threatening condition in children. Failures of response to immunosuppressive medications and radiological intervention also lead to high mortality. Some reports suggested that tumor necrosis factor (TNF) might have role in the inflammation of this disease. After an English-language literature review, this is the first case report in children of recurrent abdominal-ruptured aneurysms with a failure of conventional therapy but successfully treated with anti-TNF-α monoclonal antibody. We herein describe a 9-year-old girl who presented with chronic abdominal pain, hypertension, and massive lower gastrointestinal bleeding. The disease was refractory to conventional treatment, including administration of a corticosteroid, cyclophosphamide, and intravenous immunoglobulin, and recurrent-ruptured aneurysms developed in the gastrointestinal tract. Arterial embolization during angiography resulted in temporary improvement of the gastrointestinal bleeding. Infliximab, a chimeric anti-tumor necrosis factor-α monoclonal antibody, was initiated and resulted in disease remission with resolution of the gastrointestinal bleeding and abdominal pain. Anti-TNF therapy might be another treatment option for refractory disease to prevent ongoing inflammation that could lead to aneurysmal dilatation or even rupture. However, early recognition of refractory disease and aggressive treatment in the early course of the disease are crucial to reduce morbidity and mortality.

Early reduction of serum interleukin-6 levels as a predictor of clinical remission in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin (IL)-6 is the main proinflammatory cytokine in systemic juvenile idiopathic arthritis (SJIA). OBJECTIVE: To determine if serial changes in serum IL-6 levels can predict outcomes of SJIA patients. METHODS: This was a retrospective cohort study. Medical records of patients aged 2-19 years with active SJIA between January 2012 and February 2014 were reviewed. Baseline characteristics were recorded at enrollment. Serum IL-6 levels were measured at enrollment and at 2-4 weeks, 6-8 weeks, 3 months, and 6 months thereafter. Treatment response and clinical remission were assessed after 2 years of follow-up. RESULTS: Of the 35 patients with active SJIA, 16 were in remission at the end of the study. IL-6 levels in the remission group returned to normal within 6 months, whereas they remained persistently high in the non-remission group. At the 3-month follow-up, patients were assigned to groups A and B based on reductions in serum IL-6 levels of >50% and ≤50%, respectively. At the end of the study, more patients in group A (72.2%) than in group B (17.6%) achieved clinical remission (p < 0.05). After multivariate analysis, a >50% reduction in serum IL-6 levels at the 3-month follow-up visit was a predictor of clinical remission at 2 years (odds ratio 22.74, 95% confidence intervals 2.16-239.85, p < 0.01). CONCLUSIONS: An early reduction in serum IL-6 levels is significantly associated with clinical remission at 2 years in SJIA patients. Monitoring of serial changes in serum IL-6 levels is beneficial for predicting clinical remission.

Macrophage activation syndrome: early diagnosis is key.

Macrophage activation syndrome (MAS) is a life-threatening condition, and it is a subset of hemophagocytic lymphohistiocytosis (HLH). The clinical features include a persistent high-grade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and a sepsis-like condition. From the clinical features, it is usually difficult to differentiate between a true sepsis, disease flare-ups, or MAS. Although the laboratory abnormalities are similar to those of a disseminated intravascular coagulation, which shows pancytopenia, coagulopathy, hypofibrinogenemia, and an elevated d-dimer test, it can also be a late stage of MAS. Currently, MAS is still underrecognized and usually results in delayed in diagnosis, which leads to high morbidity and mortality. This literature review was conducted in the context of the clinical manifestations and the laboratory abnormalities in MAS, which might provide some clues for an early diagnosis. The best ways for an early recognition and a satisfactory diagnosis were based on the relative changes in the overall parameters from the baseline, together with a thorough and continuous physical examination for these kinds of patients. At present, diagnostic criteria have been proposed for HLH, MAS-associated systemic juvenile idiopathic arthritis, and an MAS-associated systemic lupus erythematosus. Therefore, selecting the proper diagnostic criteria for use is essential because not all of the criteria are suitable for every autoimmune disease.

The Thai 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 Thai 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 104 JIA patients (45.2% systemic JIA, 10.6% oligoarticular, 9.6% RF negative polyarthritis, 34.6% other categories) and 102 healthy children, were enrolled in one paediatric rheumatology centre. Notably, none of the enrolled JIA patients is affected with psoriatic arthritis or undifferentiated arthritis. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed satisfactory psychometric performances. In conclusion, the Thai 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.

The comparisons between thermography and ultrasonography with physical examination for wrist joint assessment in juvenile idiopathic arthritis.

OBJECTIVE: This study aimed to assess infrared thermography (IRT) and ultrasonography (US) for detecting wrist arthritis in juvenile idiopathic arthritis (JIA) patients. Although IRT could help us in detecting joint inflammation, IRT studies in JIA patients with wrist arthritis are still limited. Currently, no validated US criteria exist for detecting arthritis, and the most useful parameters between gray-scale ultrasound (GSUS) or power Doppler ultrasound (PDUS) remain unclear. APPROACH: Forty-six JIA patients were included in this study. Detecting wrist arthritis at varying degrees using IRT and US were compared with physical examination. MAIN RESULTS: Sixteen patients had previous wrist arthritis that is currently inactive and 30 still had wrist arthritis. The median ages (IQR) were 7.7 (4.3) and 10.2 (4.8) years, respectively. Fifteen healthy participants were included, with a median age (IQR) of 9.2 (2.0) years. Using IRT, mean temperature (T mean) and maximum temperature (T max) at skin surface in the region of interest (ROI) in the arthritis group were higher than in the inactive group and the healthy controls with p < 0.05. When patients with arthritis were subgroup analyzed by disease severity based on physical examination, the moderate to severe arthritis had T mean and T max higher than the mild arthritis group with statistical significance. The heat distribution index (HDI), two standard deviations of all pixel temperature values in the ROI, in the moderate to severe arthritis group was higher than in the healthy controls (p = 0.027). The receiver operating characteristic analysis in arthritis detection revealed diagnostic sensitivity of 85.7% and 71.4% and specificity of 80.0% and 93.3% at cut-off points of T mean ⩾ 31.0 °C and T max ⩾ 32.3 °C, respectively. For US, GSUS and PDUS are useful in detecting arthritis, providing high sensitivity (83.3%) and specificity (81.3%). SIGNIFICANCE: Our study demonstrated that both IRT and US were applicable tools for detecting wrist arthritis.