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.

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.

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.

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.

De novo food allergy in pediatric liver transplantation recipients.

BACKGROUND: Food allergy (FA) prevalence is increasing in pediatric liver transplantation (LT). However, the clinical course is still limited. OBJECTIVE: This retrospective cohort study aimed to identify the prevalence, risk factors, and the natural history of de novo FA in children post LT. METHODS: Medical records of pediatric LT recipients from Jan 2001 - Dec 2014 were reviewed. De novo FA was diagnosed by symptoms after exposure to culprit food occurring after LT, and improvement after diet elimination. FA was confirmed if reproduced symptoms after re-challenge or documented sensitization or indicated gastrointestinal eosinophilia. RESULTS: Among 46 post LT children, 54.3% developed de novo FA at a median time of 12.2 months [Interquartile range (IQR) 6.2, 21.3 months] post LT. The confirmed FA was 39.1%. Gastrointestinal symptom was the most common manifestation followed by skin, anaphylaxis, and others. Culprit foods were cow's milk, shellfish, egg, wheat, soybean, peanut, coconut, fish and monosodium glutamate. The risk factors of FA were transplantation during age below 2 years [hazard ratio (HR), 2.62; 95% confidence interval (CI), 1.04 - 6.59; p = 0.03), atopic history in family (HR, 5.67; 95% CI, 1.33 - 24.12; p = 0.01), and Epstein-Barr (EBV) viremia (HR, 2.39; 95% CI, 1.02 - 5.63; p = 0.04). CONCLUSIONS: de novo FA in pediatric LT is not uncommon. Age at LT younger than 2 years, family history of atopy, and EBV viremia are associated with developing FA. Development of tolerance after elimination culprit diets for 3 years is similar to general population.

Paediatric rheumatology clinic population in Southeast Asia: are we different?

Objectives: To examine the descriptive epidemiology of the patient population referred to paediatric rheumatology centres (PRCs) in Southeast Asia (SEA) and to compare the frequency of conditions encountered with other PRC populations. Methods: A web-based Registry for Childhood Onset Paediatric Rheumatic Diseases was established in 2009 and seven PRCs in four SEA countries, where paediatric rheumatologists are available, participated in a prospective 24 month data collection (43 months for Singapore). Results: The number of patients analysed was 4038 (788 from Malaysia, 711 from the Philippines, 1943 from Singapore and 596 from Thailand). Over 70% of patients evaluated in PRCs in Malaysia, the Philippines and Thailand had rheumatic diseases (RDs), as compared with one-half of the proportion seen in Singaporean PRCs, which was similar to the Western PRC experience. Among RDs diagnosed (n = 2602), JIA was the most common disease encountered in Malaysia (41%) and Thailand (61%) as compared with systemic vasculitides in the Philippines (37%) and Singapore (35%) among which Henoch-Schönlein purpura was the most prevalent. SLE and related diseases were more common, but idiopathic pain syndrome and abnormal immunological laboratory tests were rarer than those seen in the West. JIA subtype distributions were different among countries. Among non-RDs (n = 1436), orthopaedic and related conditions predominated (21.7-59.4%). Conclusion: The frequencies of RDs seen by SEA PRCs were different from those in the West. Systemic vasculitides and SLE were common in addition to JIA. Paediatric rheumatologist availability and healthcare accessibility partially explain these observed discrepancies.

Myocardial performance index in active and inactive paediatric systemic lupus erythematosus.

OBJECTIVES: To evaluate cardiac structure and function in paediatric SLE patients without clinical evidence of cardiovascular disease in active and inactive diseases. METHODS: Patients aged ≤20 years who fulfilled the diagnostic criteria of active SLE underwent transthoracic echocardiography to evaluate cardiac structure and function, and were then followed up echocardiographically every 3-4 months until SLE disease was inactive. Patients with heart failure, myocarditis, pericarditis, endocarditis, coronary artery disease, or abnormal structural heart disease were excluded. RESULTS: Twenty-six active SLE patients, mean age 13.2±3.3 years, of whom 20 were female (77%), were enrolled. Most patients had cardiac abnormalities especially LV global dysfunction assessed by left ventricular myocardial performance index (LV MPI). LV MPI by conventional method, by tissue Doppler imaging (TDI) at medial and lateral mitral valve annulus were significantly decreased when compared to LV MPI in patients with inactive disease (0.44±0.14 vs. 0.30±0.05, 0.52±0.09 vs. 0.36±0.04, and 0.51±0.09 vs. 0.35±0.05, p<0.001). Using receiver operating characteristic, LV MPI cut-off at 0.37, 0.40, and 0.40 by conventional, medial TDI, lateral TDI had sensitivity and specificity of 90% and 84%, 90% and 96%, 90% and100%, respectively. CONCLUSIONS: Left ventricular global dysfunction was found to be common in paediatric patients with active SLE. LV MPI by TDI might be useful to diagnose active SLE in paediatric patients.

Comparisons of the outcomes between early and late tocilizumab treatment in systemic juvenile idiopathic arthritis.

Around 40% of systemic juvenile idiopathic arthritis (SJIA) in Thailand is steroid dependent or fails to respond to conventional therapy; therefore, tocilizumab (TCZ), a humanized anti-IL-6 receptor antibody, was indicated in these patients. Due to financial problems, some patients cannot receive TCZ treatment immediately following failure of the conventional treatment occurs, leading to disability and poor quality of life. Therefore, this study focused on the outcomes between early and late TCZ treatment in SJIA patients. This was an observational study. Baseline characteristics and disease severity were collected. Patients were divided into the early TCZ treatment group and the late TCZ treatment group. The outcomes of this study were the remission rates by the end of the study and treatment response using the American College of Rheumatology Pediatric (ACR Pedi) 30, 50, 70 criteria at 3, 6, 9, and 12 months after TCZ initiation. Descriptive analyses were conducted to determine the outcomes. Twenty-three SJIA patients were included in this study. At the end of this study, patients in the early TCZ treatment had a remission rate of 54.5%, whereas none in the late TCZ treatment achieved remission. At the 12-month follow-up, 10 patients (91%) in the early TCZ treatment group and 6 patients (50%) in the late TCZ achieved ACR Pedi 70. The outcomes of TCZ treatment in SJIA patients depend on the time to start TCZ treatment. In the early TCZ treatment, SJIA patients had a higher remission rate and better treatment response than patients who received TCZ treatment late.

Clinical improvement of renal amyloidosis in a patient with systemic-onset juvenile idiopathic arthritis who received tocilizumab treatment: a case report and literature review.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a common rheumatic disease in children and adolescents. Although JIA may cause secondary amyloidosis, this is a rare complication in patients with JIA and other rheumatic diseases. Many previous studies have revealed that common heterozygous or homozygous mutations in the MEFV gene are associated with systemic-onset JIA (SJIA). CASE PRESENTATION: We herein report a case involving a 19-year-old female patient with difficult-to-control SJIA. She developed progressive proteinuria without clinical signs or symptoms of edema. Renal amyloidosis was diagnosed by renal pathologic examination, which demonstrated deposition of eosinophilic amorphous material in the interlobular arteries, arterioles, and interstitium. Electron microscopy showed fibrillary material deposits with a diameter of 8 to 10 nm. A heterozygous E148Q mutation in the MEFV gene was identified. Conventional disease-modifying anti-rheumatic drugs and etanercept had been used to treat the SJIA, but the disease could not be controlled. Therefore, we decided to start tocilizumab to control the disease activity. However, the patient was unable to receive a standard dose of tocilizumab in the early period of treatment because of socioeconomic limitations. Her disease course was still active, and proteinuria was found. Therefore, tocilizumab was increased to a dose of 8 mg/kg every 2 weeks (standard dose of SJIA), and the patient exhibited a clinical response within 3 months. CONCLUSION: Refractory SJIA associated with renal amyloidosis is an uncommon cause of proteinuria in adolescents. Tocilizumab may be a beneficial treatment for renal amyloidosis in patients with SJIA.

Pediatric anaphylaxis: triggers, clinical features, and treatment in a tertiary-care hospital.

BACKGROUND: Anaphylaxis is a life-threatening condition. There are limited data about its etiology and clinical characteristics in Asian children with anaphylaxis. OBJECTIVE: To investigate triggers, presenting symptoms, treatment and clinical course of anaphylaxis in Thai children. METHOD: Medical record of children who were diagnosed with anaphylaxis between 2004 and 2013 at Ramathibodi Hospital, Bangkok, Thailand were reviewed. RESULTS: One hundred-seventy two episodes of anaphylaxis occurred in 160 children (91 boys, 69 girls) aged 3 months to 18 years. Anaphylaxis increased from 2.7 cases/1000 pediatric admission to 4.51 cases/1000 pediatric admission between 2004-2008 and 2009-2013. The main causes were food (34.92%), drug (33.1%), blood components (23.8%), insect sting (9%), and unidentified causes (2.8%). Allergy to the triggers was known prior to anaphylaxis in 42 episodes (24.6%). Treatment consisted of epinephrine intramuscularly (93.8%), corticosteroids (92.5%), H1antihistamines (96%), H2antihistamines (50%), and ß2agonists nebulization (35.1%). Biphasic anaphylaxis occurred in 8.7% of the documented episodes and severe anaphylaxis in 34.3% of the documented episodes. Biphasic anaphylaxis and severe anaphylaxis were associated with fewer administrations of intramuscular epinephrine (OR 0.08 [95% CI 0.014-0.43]; p =0.01 and OR 9.36 [95% CI 2.5-34.7]; p <0.001 respectively). There were no fatality cases. There were associations between triggers of anaphylaxis and atopic histories, patients with severe anaphylaxis and cardiovascular involvement (p <0.01). CONCLUSIONS: The incidence of anaphylaxis in Thai children is increasing. Anaphylaxis in children commonly occurred without the histories of prior reaction to the causative agent. Less frequent treatment with intramuscular epinephrine was associated with biphasic and severe anaphylaxis. A better knowledge of patterns and causes of anaphylaxis might contribute to a better management.

Direct medical cost of Thai pediatric asthma management: a pilot study.

BACKGROUND: The prevalence of asthma in Bangkok increased steadily over the last couple of decades and warrants an assessment of the costs associated with its treatment, particularly in the case of children. OBJECTIVE: To estimate the direct medical costs of asthma care in children at the Allergy unit of the Department of Pediatrics, Ramathibodi hospital. METHODS: In this retrospective study, we included asthmatic children aged less than 20 year-old having visited the allergy unit at least 4 times in 12 months between January and December, 2011. Cost data, retrieved from the allergy unit electronic database included billing invoices of inpatient care, outpatient and emergency room visits. From this dataset we estimated drug costs, physician and nursing services, diagnostic tests and procedures, supplies and room charges, and assessed an overall asthma-related direct medical cost. RESULTS: Ninety-seven asthmatic children (aged 11.5 ± 3.7 years) were included in the study. Annual median direct medical cost was 8,537.9 Baht or 278 USD per patient. Annual direct medical cost was the highest in patients younger than 5 years old (p < 0.001). Moreover, expenses of patients who had at least one exacerbation increased significantly compared to patients without exacerbation (p = 0.02). Furthermore, direct medical cost was the highest when patients had exacerbation requiring hospitalization (p = 0.03). CONCLUSIONS: Cases of patients having asthma exacerbation or being diagnosed with asthma before 5 years of age were associated with higher treatment expenses. Policies developed to achieve asthma control and prevention should identify young children and patients presenting risk factors for asthma exacerbation as high risk groups deserving particular attention.

In vitro cytokine changes after pediatric liver transplantation.

BACKGROUND: Patients with chronic liver disease have been shown to have impaired immune statuses. Liver transplantation (LT) is the standard treatment for end-stage liver disease patients and immunosuppressive drugs are commonly used to prevent graft rejection. There is an increasing evidence of de novo food allergies post LT. OBJECTIVE: To investigate the cytokine response of peripheral blood mononuclear cells (PBMCs) of pediatric LT recipients before and six months after transplantation. METHOD: PBMCs collected before and six months after LT were stimulated with phytohemagglutinin (PHA), beta-lactoglobulin (BLG), tacrolimus (Tac), dexamethasone (Dex), and a combination of BLG and Dex (B+D), BLG and Tac (B+T), BLG and Tac plus Dex (B+T+D). Culture supernatants were measured for IL-5, IFN-γ and IL-10. Blood for liver function tests, complete blood counts, total IgE and specific IgE (sIgE) to cow's milk were recorded. RESULTS: A total of five pediatric LT recipients were enrolled in the study. There were no food allergy cases. Total IgE and sIgE to cow's milk decreased significantly after LT. After transplantation, there was a significant increase in IL-5, IFN-γ and IL-10 in culture supernatants of PHA-stimulated PBMCs. Among different stimulations in post transplantation's PBMCs, the level of IL-5 significantly increased in B+D was suppressed with the combination of B+T+D. The level of IL-10 significantly increased in all conditions containing BLG both before and after transplantation. CONCLUSION: There was an improvement of the in vitro-cytokine responses after liver transplantations. Immunosuppressive drugs used in post transplantation had an effect on the cytokine responses.

Assessing the efficacy of a novel temperature and humidity control machine to minimize house dust mite allergen exposure and clinical symptoms in allergic rhinitis children sensitized to dust mites: a pilot study.

BACKGROUND: House dust mite avoidance is advised in dust mite sensitized patients to decrease the risk to develop allergic symptoms. Maintaining a relative humidity (RH) of less than 50% in households is recommended to prevent dust mite proliferation. OBJECTIVE: To investigate the efficacy of a novel temperature and humidity machine to control the level of dust mite allergens and total nasal symptom score (TNSS) in dust mite sensitized allergic rhinitis children. METHOD: Children (8-15 years) with dust mite sensitized persistent allergic rhinitis (AR) were enrolled. The temperature and humidity control machine was installed in the bedroom where the enrolled children stayed for 6 months. TNSS was assessed before and every month after machine set up and the level of dust mite allergen (Der p 1 and Der f 1) from the mattress were measured before and every 2 months after machine set up using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 7 children were enrolled. Noticeable reduction of Der f 1 was observed as early as 2 months after installing the machine, but proper significant differences appeared 4 months after and remained low until the end of the experiment (p <0.05). Although no correlation was observed between TNSS and the level of dust mite allergens, there was a significant reduction in TNSS at 2 and 4 months (p <0.05) and 70% of the patients were able to stop using their intranasal corticosteroids by the end of the experiment. CONCLUSIONS: The level of house dust mite in mattresses was significantly reduced after using the temperature and humidity control machine. This machine may be used as an effective tool to control clinical symptoms of dust mite sensitized AR children.

Cow's milk protein allergy: immunological response in children with cow's milk protein tolerance.

OBJECTIVE: To study changes in immunological responses in patients with CMPA during symptomatic and asymptomatic episodes of cow's milk protein tolerance status. METHODS: 27 CMPA patients were enrolled and underwent diagnostic evaluation, including CM challenge test, skin prick test and specific IgE to CM. Blood samples were collected in two periods from those who became tolerant (n = 13) and those with persistent CMA (n = 14), in order to measure in vitro PBMC responses to cow's milk protein (IL-10, IFN-γ, IL-5), IgG4 to ß-lactoglobulin, casein, BLG-IgG4/IgE ratio and the CAS-IgG4/IgE ratio. RESULTS: Seventy percent of CMPA patients in our study were male with a mean age at diagnosis of 8 months and mean age of onset of 3 months. The reaction time to CM ranged from within 7 minutes to within 14 days. Positive IgE-sensitization was defined as either a specific IgE to CM of more than 0.35 kUA/L (N=11) or SPTs positive for CM and/or fresh cow's milk (N=20). Forty-eight percent of the patients (n = 13) could tolerate CM by 13.38 months (8-19 months). Mean specific-IgE levels to CM were 4.1 kUA/L (range 0.35-14.3 kUA/L). Determination of the cytokine (IL-10, IFN-γ, IL-5) response to BLG revealed significantly higher IL-10 levels during the tolerance phase (212.93 vs 142.46 pg/ml, P = .011). There was a significant increase in BLG-IgG4 and the BLG-IgG4/IgE ratio in the tolerance phase when compared to the symptomatic phase. CONCLUSIONS: IL-10, BLG-IgG4 and the BLG-IgG4/IgE ratio were higher in CMPA patients during the tolerance phase compared to the symptomatic phase.

Use of transient elastography to assess hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis during methotrexate treatment.

OBJECTIVES: This study aimed to assess the prevalence and identify predictors of hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis (JIA) during methotrexate treatment. METHOD: This cross-sectional study included JIA patients who had received methotrexate for > 1 year. Laboratory data including liver chemistry and lipid profiles were collected. Liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) were determined by transient elastography. Significant hepatic fibrosis was defined as LSM > 7 kilopascal (kPa), and hepatic steatosis was defined as CAP > 225 decibel/meter (dB/m). Logistic regression analysis was performed to identify predictors associated with hepatic steatosis and fibrosis. RESULTS: Of 60 patients, 66.7% were female, and the median age (IQR) was 12.8 (10.6-15.0) years. The median duration of methotrexate usage (IQR) was 45 (22-85) months, and the median cumulative dose of methotrexate (IQR) was 3768 (1806-6466) mg. The median LSM (IQR) and CAP (IQR) were 4.1 (3.4-4.6) kPa and 191.0 (170.3-223.8) dB/m, respectively. No patients had transient elastography-defined hepatic fibrosis, whereas 21.7% had hepatic steatosis. A body mass index Z-score > 1 (OR 5.71 [95%CI 1.31-24.98], p = 0.021) and higher cumulative dose of methotrexate (OR 1.02 [95%CI 1.00-1.04], p = 0.041) were associated with hepatic steatosis, whereas the cumulative dose of steroids was not (OR 1.00 [95%CI 1.00-1.01], p = 0.097). CONCLUSIONS: Hepatic steatosis is common among JIA patients receiving methotrexate, but none had transient elastography-defined hepatic fibrosis. Overweight/obese JIA adolescents and patients with a high cumulative dose of methotrexate are at risk for hepatic steatosis. Key Points •Long-term low-dose methotrexate usage and the concomitant use of other DMARDs did not increase the risk of hepatic fibrosis in JIA patients. •The prevalence of hepatic steatosis in JIA patients receiving methotrexate was higher than in a healthy pediatric population. •Overweight/obesity and a higher cumulative dose of methotrexate were predictors of hepatic steatosis.

The inequity of global healthcare in pediatric rheumatology.

In pediatric rheumatology, global health inequity relates to the uneven distribution of healthcare resources, accessibility, and health outcomes among children with rheumatic conditions across various countries, regions, and socioeconomic groups. This inequity can manifest in various ways. This review article provides an overview of common rheumatic diseases, such as juvenile idiopathic arthritis and systemic lupus erythematosus, which significantly contribute to and are affected by disparities in global healthcare. Subsequently, we delve into the inequalities in accessing patient care, encompassing issues related to diagnosis and treatment. Additionally, we address challenges in educational advancement and identify research gaps within the field of pediatric rheumatology. We also reveal successful global collaborations, such as a Global Task Force for Pediatric Musculoskeletal Health and special working groups among international organizations, aimed at bridging the disparities gap. Through these efforts, we try to enhance understanding, cooperation, and resource allocation to ensure equal access to quality care worldwide for children with rheumatic conditions. Futhermore, we present a case study from Thailand, highlighting their successful initiatives in developing pediatric rheumatology within their healthcare system.

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.

Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children.

BACKGROUND: Aromatic anticonvulsant-induced severe cutaneous adverse drug reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), are fatal immune-mediated adverse drug reactions. CYP2C19, a cytochrome P450 isoform, plays a role in metabolic rate of aromatic anticonvulsant. HLA-B*1502 has also been demonstrated to be associated with carbamazepine-induced SJS-TEN. METHODS: Forty case patients who were diagnosed with SCARs after initiation of phenobarbital (PB), phenytoin (PHT), or carbamazepine (CBZ) for 1-8 wk and forty control patients who received PB, PHT, or CBZ at least 2 months with no adverse drug reactions were enrolled in the study. The genotypes of CYP2C19*1, CYP2C19*2, and HLA-B*1502 were analyzed using allele-specific polymerase chain reaction technique. Clinical characteristics of SCARs patients who used different drugs were also analyzed. RESULTS: There was no significant difference in sex, onset of symptoms, laboratory results, treatment, and length of stay among patients with SCARs due to PB, PHT, or CBZ. The patients with CYP2C19*2 variant had a trend to have a likelihood to develop SCARs more than the patients with CYP2C19 wild type (OR = 2.5, 95% CI (0.96-67.3) p = 0.06). In subgroup analysis, the patients with CYP2C19*2 variant were at four times increased risk of SCARs from phenobarbital more than the patients with CYP2C19 wild type (OR = 4.5, 95% CI (1.17-17.37) p < 0.03). There was no association between the HLA-B*1502 and aromatic anticonvulsant-induced severe cutaneous adverse reactions (SCARs). CONCLUSION: CYP2C19*2 variant may play a role in the genetic predisposition of SCARs from phenobarbital.

Comparison of conjunctival and nasal provocation tests in allergic rhinitis children with Dermatophagoides pteronyssinus sensitization.

BACKGROUND: Nasal provocation tests (NPTs) are indicated in confirming the diagnosis of allergic rhinitis if the clinical history, skin tests or sIgE are inconclusive. NPTs are time- consuming, technically difficult and expensive to perform. Consequently, conjunctival provocation tests (CPTs), which are easier, cheaper and safer should be considered as an alternative method. No recent study has compared CPTs with NPTs in allergic rhinitis children. OBJECTIVE: To compare CPTs with NPTs in allergic rhinitis children with house dust mite sensitization METHODS: Fifty-five children with allergic rhinitis were included. Thirty-six children had positive skin prick tests (SPTs) to Dermatophagoides pteronyssinus (Dp). NPTs were performed by spraying 0.1 ml of Dp extract with concentrations of 50, 200 and 500 AU/ml to each nostril at 15 minute interval. The clinical symptom scores, anterior rhinomanometry results and nasal peak flow testing were performed to assess the responses. For CPTs, 0.1 ml of the same concentration of allergen extract was droppedinto one eye and the control solution was dropped into the other. The responses were assessed by clinical symptom scores. The tests were stopped when the subject reported a positive response, or continued to the maximum concentration. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CPT compared with NPT are 97.1% (84.7-99.9), 90.5% (69.6-98.8), 94.3% (80.8-99.3), 95% (75.1-99.9) and 94.5 (84.9-98.9), respectively in all patients. Among individual allergic rhinitis subjects the sensitivity, specificity, PPV and NPV are 100%. CONCLUSIONS: CPT can be an alternative test for NPT in allergic rhinitis children with house dust mite sensitization, even if they do not have conjunctival symptoms.