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.

Sarcoplasmic Myxovirus Resistance Protein A: A Study of Expression in Idiopathic Inflammatory Myopathy.

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases affecting primarily proximal muscles. Major subtypes include dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy and antisynthetase syndrome. Overexpression of sarcoplasmic myxovirus-resistance protein A (MxA) has been observed in muscle biopsy specimens of dermatomyositis but is rarely seen in other subtypes of IIM and other myopathies. Objective: We evaluate the expression of sarcoplasmic MxA and its diagnostic value in IIM and other myopathies. Methods: One hundred and thirty-eight muscle biopsy specimens with the diagnosis of IIM and other myopathies from 2011 to 2020 were reviewed and stained for MxA by immunohistochemistry. The difference of the expression of MxA between IIM and other myopathies was analyzed by Fisher's exact test, and the sensitivity and specificity of MxA immunohistochemistry in the diagnosis of IIM were assessed. Results: MxA protein was positive in 16/138 (11.6%) specimens. All 12 dermatomyositis specimens positive for MxA protein were positive in perifascicular area pattern. Only dermatomyositis specimens had a significantly higher percentage of positive sarcoplasmic MxA expression than specimens of other subtypes of IIM (p<0.001). Sarcoplasmic MxA expression for dermatomyositis diagnosis had a sensitivity of 46.15% (95% CI 26.59-66.63%) and a specificity of 94.44% (95% CI 81.34-99.32%) with the positive and negative likelihood ratio of 8.31 (95% CI 2.03-34.01) and 0.57 (95% CI 0.40-0.82), respectively. Conclusion: The MxA immunohistochemistry is highly specific for dermatomyositis and should be added to a routine inflammatory panel of muscle biopsy. MxA expression should be cautiously interpreted to avoid pitfalls.

Immunogenicity of Hepatitis B Vaccine in Pediatric Systemic Lupus Erythematosus Patients.

BACKGROUND: Pediatric patients with systemic lupus erythematosus (SLE) are at increased infectious risk caused by underlying immunologic dysregulation and immunosuppressive therapy. Hepatitis B virus (HBV) could be reactivated during the immunosuppressive treatment in patients with past HBV infections. Information on immunogenicity after hepatitis B (HB) immunization and reimmunization are still scarce. METHODS: SLE patients 5-18 years of age who had completed a primary HB immunization were enrolled. Anti-HBs levels at enrollment and after each vaccine dose were determined. Patients with anti-HBs levels < 10 mIU/mL were administered 1 booster dose. After 1 booster dose, patients with negative anti-HBs levels were administered 2 more booster doses. RESULTS: Ninety-three SLE patients were enrolled. The prevalence of seroprotection assessed by anti-HBs > 10 mIU/mL after completion of a primary HB immunization was 25.8% (95% CI: 17.2-34.4). Lupus nephritis was associated with unprotective anti-HBs levels [odds ratio (OR): 4.341; 95% CI: 1.044-18.040]. The anti-HBs seroconversion was 72.3% (95% CI: 61.5-83.0) after 1 booster dose and increased up to 93.4% (95% CI: 86.9-98.4) after 3 booster doses. SLE Disease Activity Index-2000 score ≥ 4 (OR: 4.625; 95% CI: 1.45-14.80) was significantly associated with nonseroconversion after the first booster dose. Hypocomplementemia before the first and second booster doses (OR: 27; 95% CI: 1.26-578.35) was significantly associated with nonseroconversion after 3 booster doses. CONCLUSIONS: All pediatric SLE patients should be evaluated for HBV serological status before immunosuppressive treatment. SLE patients with SLE Disease Activity Index-2000 score > 4 should need 3 booster doses if their anti-HBs level was < 10 mIU/mL.

Effect of educational brochure compared with video on disease-related knowledge in patients with juvenile idiopathic arthritis: A randomized controlled trial.

Introduction: Patient education plays an important role in the management of chronic diseases such as juvenile idiopathic arthritis (JIA). This study compared the effectiveness of a brochure and a video regarding JIA-related knowledge immediately after the intervention, and at 4 weeks post-intervention. Methods: A prospective randomized controlled trial was conducted. Patients with JIA or parents were randomized to receive education from either a brochure (n = 50) or a video (n = 50) at the clinic. Participants answered questionnaires about disease-specific knowledge before the intervention (T0), immediately after the intervention (T1), and at follow-up 4 weeks later (T2). The questionnaire comprised 15 multiple-choice questions. Final scores ranged from 0 to 15, and were scaled from 0% to 100% to calculate the percentage of knowledge scores. Ninety participants completed the questionnaire at T2 (42 in the brochure and 48 in the video group). Results: The mean percentage of knowledge scores at T0 was not significantly different between the brochure group and the video group. At T1, the mean percentage of knowledge scores was significantly higher in the video group compared with the brochure group (86.7 ± 12.9% vs. 76.0 ± 21.4%, p = 0.003). Among parents with an educational level below secondary school, the mean percentage of knowledge scores at T1 was significantly higher in the video group compared with the brochure group (83.5 ± 14.4% vs. 69.1 ± 23.2%, p = 0.006). Participants in both groups had significantly higher mean percentage of knowledge scores at T2 compared with T0 (72.7 ± 20.3% vs. 51.1 ± 24.7%, p < 0.001 in the brochure group and 78.3 ± 15.7% vs. 56.1 ± 21.9%, p < 0.001 in the video group). There was no significant difference in the mean percentage of total score change between T2 and T1 between the brochure and video groups (-4.7 ± 13.3% vs. -8.5 ± 11.0%, p = 0.152). Conclusion: The video was more effective for improving disease-related knowledge immediately post-intervention, particularly in participants with limited education. Although both educational tools had lasting effects on knowledge, the retention rate declined at 4 weeks after both interventions. Trial registration: Thai Clinical Trials Registry (TCTR)20200310004, retrospectively registered since 06/03/2020.

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.

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.

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.

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.

A retrospective study on 158 Thai patients with juvenile idiopathic arthritis followed in a single center over a 15-year period.

AIM: To determine the outcomes of juvenile idiopathic arthritis (JIA) in Thai children. METHODS: A retrospective cohort study. All JIA patients in a rheumatology clinic, Ramathibodi Hospital, between July 1997 and December 2012 were enrolled. The patient data were reviewed from medical records. At the most recent follow-up visit, patient outcomes were assessed in three aspects: disease status, functional outcomes and structural damage. RESULTS: Of 168 patients, 158 (94.0%) were assessed in disease status and functional outcomes, with 114 patients (67.9%) assessed in three aspects over 4 years of disease. The most common JIA category was systemic JIA (SJIA) (33.8%), followed by enthesitis-related arthritis (ERA) (24.8%), oligoarthritis (18.5%), rheumatoid factor (RF)-negative polyarthritis (15.3%), RF-positive polyarthritis (7.6%) and one undifferentiated arthritis. SJIA had the highest remission rate due to early diagnosis and prompt treatment compared to other categories, whereas RF-positive polyarthritis carried the worst prognosis in three aspects, followed by ERA. Moreover, ERA patients had the highest failure rate in conventional therapy, half of whom had combined treatment with biologic agents and presence of human leukocyte antigen (HLA)-B27 was a predictor for biologic treatment in ERA patients. In addition, disease duration > 2 years or failure of conventional therapy was a predictor of structural bone damage. CONCLUSIONS: SJIA had the highest remission rate, whereas RF-positive polyarthritis had the worst outcome in three aspects. Prolonged disease duration or failure of conventional therapy was a predictor of structural bone damage, while HLA-B27 was a predictor for biologic treatment in ERA patients.