Epidemiological characteristics of patients with juvenile dermatomyositis in China: a multicenter study.

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare but chronic autoimmune disease with systemic nonsuppurative inflammation. Many studies have focused on the clinical characteristics and therapy of JDM. A few studies have reported the epidemiological characteristics and social burden of JDM patients abroad, but there has been no study in China. METHODS: This study was based on the FUTang Updating medical REcords Database. Data was extracted from the registry information of inpatient medical records. The epidemiological characteristics and economic burden of Chinese JDM patients were analyzed. RESULTS: A total of 1164 JDM patients from 24 hospitals were enrolled from Jan 2016 to Dec 2021. The ratio of boys to girls was 1:1.23, and half were between 6 and 12 years old. Over half(n=629) were admitted to the hospital at least twice for intensive treatment. 20% of JDM patients suffered from lung involvement and 2.2% suffered from subcutaneous calcification. The median days of hospitalization were 10 (range 6 to 14), in addition, the median United States dollar (USD) of expense was 2370.5(1373.7,3541.9). Lung involvement was the major factor causing high inpatient burden, length of stay, and expense. Nearly, 17% of JDM patients were admitted to the hospital as emergencies, suggesting sever disease activity stage needing urgent treatment. No deaths occurred in our study. CONCLUSION: Our study documents the epidemiological characteristics and social burden of JDM patients in China, contributing to the enhanced comprehension and effective management of JDM in the country.

Clinical manifestations, treatment and prognosis of juvenile idiopathic arthritis with pulmonary involvement in China: a single centre study.

OBJECTIVES: In recent years, the distinct clinical presentations and elevated mortality rates of various subtypes of juvenile idiopathic arthritis (JIA) with pulmonary involvement have garnered significant attention. This study aimed to elucidate the clinical characteristics of pulmonary involvement in patients with JIA to improve clinicians' knowledge. METHODS: This single-centre retrospective study analysed the baseline data, treatment options, follow-up of sixty patients of JIA with pulmonary involvement in China. Patients with interstitial lung disease (ILD) were further classified in accordance with the 2013 American Thoracic Society/European Respiratory Society International multidisciplinary consensus on idiopathic interstitial pneumonia. RESULTS: Sixty patients (5.03%) with JIA were complicated with pulmonary involvement. The highest subtype was systemic JIA (sJIA, 63.3%), followed by rheumatoid factor (RF)-positive polyarthritis (pJIA, 25.0%). The incidence of macrophage activation syndrome (MAS) was 21.6%. The most common diagnosis was ILD (90%). Respiratory symptoms/signs were initially experienced by 61.7% of the patients, and respiratory support was required by 21.7%. High-resolution CT classification of sJIA revealed non-specific interstitial pneumonia (NSIP) and organising pneumonia. High-resolution CT classification of pJIA was NSIP and usually interstitial pneumonia (UIP). Patients were treated with NSAIDs, along with glucocorticoids, DMARDs, and biological agents. The survival rates after 1 and 5 years were approximately 93.3% and 90.0%, respectively. CONCLUSIONS: Patients with JIA with pulmonary involvement present with early onset, high mortality rate. JIA patients should undergo physical examination thoroughly and high-resolution CT scans, lung function tests for evaluating and monitoring the occurrence and development of pulmonary involvement in early stages to improve prognosis.

Evaluating treatment practices and challenges in systemic Juvenile Idiopathic Arthritis: a comprehensive survey analysis.

OBJECTIVE: This study aims to assess current diagnostic and management for systemic Juvenile Idiopathic Arthritis (sJIA) among physicians, evaluate the challenges encountered in diagnosis and treatment, and identify the educational needs and professional development engagements of physicians managing sJIA. METHODS: A nationwide survey was conducted from November 2023 to March 2024 across tertiary and secondary pediatric and general hospitals in China. The survey targeted physicians with at least three years of specialty experience, resulting in 310 valid responses from 25 provinces, autonomous regions, and municipalities. The survey collected data on diagnostic practices, treatment approaches, and professional development related to sJIA. Data collection was facilitated through WeChat, and statistical analysis was performed using descriptive statistics. Ethical approval was obtained from the Ethics Committee of Beijing Children's Hospital, with informed consent provided electronically by participants. RESULTS: The survey indicated that all physicians encountered suspected or confirmed cases of sJIA, highlighting its prevalence and the diagnostic challenges associated. Regarding diagnostic standards, 53.9% of physicians used the "Consensus on the Diagnosis and Treatment of sJIA and Macrophage Activation Syndrome," 18.1% followed the International League of Associations for Rheumatology (ILAR) standards, and 24.8% adhered to the Pediatric Rheumatology International Trials Organization (PRINTO) standards. In treatment strategies, glucocorticoids and IL-6 receptor monoclonal antibodies were extensively used, with the latter receiving "excellent" and "satisfactory" ratings of 46.5% and 36.1%, respectively, demonstrating high efficacy and acceptance. Main challenges included high treatment costs, complexity of diagnosis, patient compliance issues, and potential long-term side effects of biologics. Additionally, 126 doctors (40.7%) actively participated in more than three academic conferences or systematic learning courses related to sJIA, indicating a strong demand for ongoing education, particularly in new treatment developments and diagnostic skills. CONCLUSION: The findings emphasize the necessity for standardized diagnosis and customized treatment plans tailored to patient-specific conditions in managing sJIA. Key Points • The survey highlights the prevalence and clinical challenges of sJIA among physicians, emphasizing the importance of vigilant diagnosis, multi-system involvement, and differential diagnosis to improve treatment outcomes and patient quality of life.

[Clinical diagnosis of group A streptococcal pharyngitis and progress in the application of scoring systems]. / A族链球菌咽炎的临床诊断及评分制的应用进展.

Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.

Case Report: Infant-onset Degos disease with nervous system involvement and a literature review.

Degos disease also known as malignant atrophic papulosis (MAP), is an autoinflammatory disease that mainly affects small- to medium-sized arteries. Gastrointestinal and nervous system are most commonly affected systems. Herein, we reported a case of Degos disease with disease onset during infantile and had severe neurological involvement.

Long noncoding nuclear enriched abundant transcript 1_2 is a promising biomarker for childhood-onset systemic lupus erythematosus.

Importance: Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease prognosis. Objective: To assess the diagnostic value of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in childhood-onset SLE (cSLE). Methods: Fifty-seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis (JIA), and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood. Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test. Results: The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve (AUC) of 0.633 (95% confidence interval [CI], 0.524-0.742; P = 0.024) for lncNEAT1_1. The AUC of lncNEAT1_2 was 0.812 (95% CI, 0.727-0.897; P < 0.0001) to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT1_2 expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for lncNEAT1_1. Interpretation: The expression of lncNEAT1_2 was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.

Age-related differences in clinical and laboratory characteristics of childhood-onset systemic lupus erythematosus: Pre-puberal-onset SLE is prone to delayed diagnosis.

OBJECTIVE: This study aimed to analyze age-specific characteristics of childhood-onset systemic lupus erythematosus (cSLE) at a health center in China. METHODS: The children with SLE were grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years), and adolescence (14-18 years). The retrospective study included patients with cSLE diagnosed at the Beijing Children's Hospital between 2013 and 2021. RESULTS: A total of 675 females and 178 males were eligible for inclusion in this study. Among them, 160 patients were diagnosed during pre-puberty, 635 during peri-puberty, and 58 during adolescence. The female-to-male ratio of pre-pubertal, peri-pubertal, and adolescent diagnosis was 3.5: 1, 3.6: 1, and 7.28:1, respectively. The median time from onset to diagnosis during the pre-puberal period was 3.0 (IQR 1.0-24.0 months), which was longer than that during the peri-puberal period (1.4; IQR 0.7-4) months and adolescence (1.0; IQR 0.4-2) months (p = <.0001). The proportion of LN in patients diagnosed during the peri-puberal period (304, 46.6%) and during adolescence (27, 47.9%) was higher than that of patients diagnosed during the pre-puberal period (59, 36.9%) (p = .044). 46 (28.8%), 233 (36.7%), and 32 (55.2%) of children diagnosed during the pre-pubertal period, peri-pubertal period, and adolescence, respectively, suffered from leukopenia. CONCLUSION: The proportion of renal involvement and leukopenia in the pre-pubertal group was lower than that of the pubertal group and adolescent group. More importantly, the younger the age of the patient, the more likely the diagnosis to be delayed.

Janus kinase inhibitor, tofacitinib, in refractory juvenile dermatomyositis: a retrospective multi-central study in China.

OBJECTIVES: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients. METHODS: A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann-Whitney U test, and chi-square test. RESULTS: Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis. CONCLUSION: In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.

Lipid profiles in patients with juvenile idiopathic arthritis: a systematic literature review and meta-analysis.

OBJECTIVE: The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA). METHODS: The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls. CONCLUSIONS: The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.

A systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanisms and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index of Nursing and Related Health Literature (EBSCOhost), science network (WOS, Clarivate Analytics), Chinese National Knowledge Infrastructure, and Chinese Biological Medical Database were systematically searched. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes environmental factors from 23 studies (6 cohorts and 17 case-control studies). Cesarean section delivery was associated with increased JIA risk (pooled relative risk [RR] 1.103, 95% CI 1.033-1.177). Conversely, maternal smoking of more than 20 cigarettes/day (pooled RR 0.650, 95% CI 0.431-0.981) and gestational smoking (pooled RR0.634, 95% CI 0.452-0.890) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research. We also highlight the challenges of combining data collected over this period due to limited study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

[Paying attention to the epidemic of group A Streptococcus infections in multiple European and American countries]. / å ³æ³¨æ¬§ç¾Žå¤šå›½Aæ—é“¾çƒèŒæ„ŸæŸ“ç–«æƒ .

At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.

Clinical characteristics of 1020 childhood-onset systemic lupus erythematosus: data from a health centre in China.

OBJECTIVES: Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterised and presents partially differently from adults. A large cSLE cohort study is lacking in China. The present study aimed to determine the clinical characteristics in a large population of patients with cSLE, and compare with adult-onset SLE (aSLE) in an SLE cohort of China. METHODS: The retrospective study included patients with cSLE diagnosed at the Beijing Children's hospital between July 2006 and October 2020. All patients met at least 4 of ACR classification criteria for SLE. In addition, data including demographic, clinical and serologic data were collected. Our data were compared with other cSLE cohorts and Chinese aSLE cohorts. RESULTS: A total of 1020 patients were included in this study, comprising 808 female and 212 male patients (female to male ratio, 3.8:1). The mean age at diagnosis of lupus was 11.1 years (range 1.0-17.2). It took on average 6 months (range 0.1-132) from first symptoms to cSLE diagnosis and over 12 months in 12% of patients. The most common primary manifestations at onset were rash (37.2%), fever (33.4%), nephropathy (14.2%) and arthritis (13.6%). The most common clinical manifestations were rash (67.9%) and fever (57.5%). 59.4% of patients had haematological involvement, 46.0% had lupus nephritis, 33.2% had arthritis. cSLE was more active and associated with more inflammation than aSLE patients. CONCLUSIONS: This study is a large single-centre study on cSLE from China and clarifies the clinical phenotype and autoantibody spectrum of cSLE. The clinical manifestations and autoantibody spectrum of cSLE are diverse, with regional and populational differences.

Early onset is an indication of the severity of DADA2 disease.

OBJECTIVE: To find indicators of disease severity and factors of early remission in patients with deficiency of adenosine deaminase 2 (DADA2). METHODS: We enrolled six DADA2 patients from six families. Direct sequencing of adenosine deaminase 2 gene (ADA2) was performed by Sanger analysis. A literature review was conducted for articles regarding paediatric DADA2. RESULTS: We found that more organs were involved in early-onset (≤1 year of age) than in late-onset (>1 year of age) DADA2 patients had high level inflammatory responses, such as elevated ESR, SF, serum amyloid A and CRP. Disease severity was not significantly different from missense and frameshift mutation. Early administration of TNF inhibitor might result in better remission and reduce recurrence. In the literature, four articles describing 51 paediatric DADA2 patients were identified. We also found that fever, stroke, peripheral nervous system involvement, hypogammaglobulinaemia and hypertension were more frequent in early onset DADA2 patients. CONCLUSION: Early-onset DADA2 may be more severe. Early administration of TNF inhibitor can effectively reduce recurrence and quickly alleviate the disease.

SAMHD1 associates with inflammation and vasculitis in paediatric-onset systemic lupus erythematosus.

OBJECTIVES: In this study, we aimed to explore the expression of the Aicardi-Goutières syndrome (AGS) mutant gene SAMHD1 in paediatric-onset systemic lupus erythematosus (pSLE), its correlations with clinical and laboratory parameters, and the relationship between its expression and the type 1 interferon (IFN) signalling pathway. METHODS: Peripheral blood from 98 pSLE patients and 44 gender and age-matched healthy individuals were examined. Gene expression levels of SAMDH1 and interferon-stimulated genes (ISGs; MxA, IRF3 and IRF7) were evaluated using real-time RT-PCR assays. RESULTS: SAMHD1 levels in pSLE patients were significantly increased compared to those in healthy donors (p<0.001). SAMHD1 was associated with serum ferritin (r=0.221, p=0.042) in pSLE patients. SAMHD1 levels were significantly increased (p<0.05) in pSLE patients with butterfly erythema, alopecia, and photosensitivity. SAMHD1 was positively correlated with MxA, IRF3 and IRF7 levels, indicating that SAMHD1 was associated with the type 1 IFN signalling pathway. CONCLUSIONS: SAMHD1 was significantly increased and correlated with MxA, IRF3 and IRF7 in pSLE patients.

Research progress in drug therapy of juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. With the gradual expansion of the incidence of JIA in the population, the pathogenesis and treatment of JIA were further explored and analyzed, and JIA has achieved some success in drug therapy. DATA SOURCES: A systemic literature search was conducted on PubMed, Cochrane Library, EMBASE, ISI Web of Science, the US National Institutes of Health Ongoing Trials Register, and the EU Clinical Trials Register. Through the searching of clinical trials of JIA in recent years, we summarized the progress of the clinical treatment of JIA. RESULTS: The main treatment drugs for JIA include non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs and biological agents. So far, a variety of biological agents targeting the cytokines and receptors involved in its pathogenesis have been gradually approved for JIA in many countries. The application of biological agents in JIA showed good efficacy and safety, bringing unprecedented experience to children and adolescents with JIA. CONCLUSIONS: The potential and advantages of biologic agents in the treatment of JIA are significant, and the application of biologic agents in the treatment of JIA will be more and more common.

Machine learning for screening and predicting the risk of anti-MDA5 antibody in juvenile dermatomyositis children.

Objective: The anti-MDA5 (anti-melanoma differentiation associated gene 5) antibody is often associated with a poor prognosis in juvenile dermatomyositis (JDM) patients. In many developing countries, there is limited ability to access myositis- specific antibodies due to financial and technological issues, especially in remote regions. This study was performed to develop a prediction model for screening anti-MDA5 antibodies in JDM patients with commonly available clinical findings. Methods: A cross-sectional study was undertaken with 152 patients enrolled from the inpatient wards of Beijing Children's Hospital between June 2018 and September 2021. Stepwise logistic regression, least absolute shrinkage and selection operator (LASSO) regression, and the random forest (RF) method were used to fit the model. Model discrimination, calibration, and decision curve analysis were performed for validation. Results: The final prediction model included eight clinical variables (gender, fever, alopecia, periungual telangiectasia, digital ulcer, interstitial lung disease, arthritis/arthralgia, and Gottron sign) and four auxiliary results (WBC, CK, CKMB, and ALB). An anti-MDA5 antibody risk probability-predictive nomogram was established with an AUC of 0.975 predicted by the random forest algorithm. The model was internally validated by Harrell's concordance index (0.904), the Brier score (0.052), and a 500 bootstrapped satisfactory calibration curve. According to the net benefit and predicted probability thresholds of decision curve analysis, the established model showed a significantly higher net benefit than the traditional logistic regression model. Conclusion: We developed a prediction model using routine clinical assessments to screen for JDM patients likely to be anti-MDA5 positive. This new tool may effectively predict the detection of anti-MDA5 in these patients using a non-invasive and efficient way.