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

ObjectivePrevious 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.MethodsThis 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).ResultsA 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).ConclusionPhysicians 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

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\u2019s alpha, interscale correlations, test\u2013retest 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

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

IntroductionVaccination 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.MethodsThis 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.ResultsA 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.ConclusionThe 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

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 (r(s) = 0.81, P < 0.0001) and galectin-9 (r(s) = 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.Transplantation and immunomodulatio

Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score

Objective 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 (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. Methods The cutoffs 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, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/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

Macrophage activation syndrome: early diagnosis is key

Butsabong Lerkvaleekul, Soamarat Vilaiyuk Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: 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. Keywords: hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, systemic lupus erythematosus, Kawasaki disease, autoimmune diseases, early diagnosi