Pediatric Rheumatology最新文献

Background: Kawasaki disease (KD) is the leading cause of acquired childhood heart disease, with untreated cases progressing to giant coronary artery aneurysms (GCAAs) in 2-3% of patients. While outcomes are well-documented in high-income settings, data from low- and middle-income countries (LMICs) remain limited. This study examines clinical profiles, treatment responses, and outcomes of children with GCAAs managed at a tertiary care center in South India.

Methods: We conducted a retrospective review of 18 children with KD-associated GCAAs (z-score >10 or diameter >8mm) treated between 2019-2024 at a tertiary care center in Kerala, India. All patients were referred from external centers with documented IVIg resistance. Treatment intensification included infliximab, corticosteroids, cyclosporine, and anakinra. Primary outcome was GCAA dimension change at last follow-up; secondary outcomes included thrombotic events, mortality, and anticoagulation cessation.

Results: The cohort comprised predominantly of males (n = 14, 77.8%) with median symptom onset at 1.1 (IQR 0.3 - 2.7) years; 50% were under one year old. While ten children (55%) experienced delayed diagnosis (>10 days after symptom onset) with median diagnosis at 11 (IQR 7 - 13.5) days; all faced delays in treatment intensification. Excluding two children lost-to-follow-up, during the median follow-up of 8.6 (5.2 - 19.4) months, complete GCAA resolution occurred in three (18.8%), reduction to small/medium aneurysms in six (37.6%), while five (31.3%) remained static. One mortality (6.3%) from myocardial infarction and a patient requiring coronary artery bypass grafting were observed. Anticoagulation was discontinued in 56.25% of children whose aneurysms resolved or reduced significantly.

Conclusion: Delayed diagnosis and treatment intensification may have contributed to mixed outcomes in this GCAA cohort. Early recognition, appropriate risk stratification, and timely immunosuppression intensification are essential to improve prognosis and reduce severe coronary complications in resource-limited settings.

Background: This study aimed to develop an alternative risk scoring system for intravenous immunoglobulin (IVIG) resistance and coronary artery aneurysm (CAA) development in patients with Kawasaki disease (KD) in Thai population.

Methods: This study is a retrospective and prospective study from January 2012 to September 2024. Data on demographics, clinical features, laboratory parameters, echocardiographic results, and outcomes were analyzed. Multivariable logistic regression was used to identify predictors for IVIG resistance and CAA.

Results: A total of 150 patients diagnosed with KD were enrolled. IVIG resistance occurred in 12.9% of cases. Independent predictors were neutrophil-to-lymphocyte ratio (NLR) ≥ 3.5 (aOR 25.0, 95%CI 2.92-214.3), neutrophil-to-lymphocyte platelet ratio (NLPR) ≥ 1.8 (aOR 11.83, 95%CI 2.24-62.28), and total bilirubin (TB) ≥ 0.9 mg/dL (aOR 3.51, 95%CI 1.21-10.23). A new risk scoring system for IVIG resistance demonstrated an AUC of 0.84 (95% CI 0.74-0.95). CAA developed in 31.6% of KD cases. Independent predictors included age ≤ 6 months (aOR 2.77, 95%CI 1.02-7.50), illness duration before IVIG ≥ 10 days (aOR 5.31, 95%CI 2.09-13.49), and C-reactive protein (CRP) ≥ 10 mg/dL (aOR 2.54, 95%CI 1.08-5.97). A new CAA risk scoring system was developed with an AUC of 0.74 (95% CI 0.64-0.83).

Conclusions: This study provided practical tools to identify high risk patients and optimize KD management. NLR, NLPR and TB are strong predictors of IVIG resistance, while younger age, delayed IVIG treatment, and high CRP are key predictors of CAA.

Background: The recent development of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have expanded the possibilities of pharmacological treatment for patients with juvenile idiopathic arthritis (JIA). The objective of this study is to evaluate trends in initial prescriptions for these targeted therapies in patients aged 0-18 years with non-systemic JIA in clinical practice. We also identified the approval dates and key regulatory changes for each medication.

Methods: A retrospective cohort study was conducted using prescription records from the Wilhelmina Children's Hospital, the largest pediatric rheumatology center in the Netherlands, analyzing data from January 2012 to December 2023. The market introduction of targeted therapies for JIA were extracted from the European Medicines Agency (EMA) database.

Results: Over an 11-year period, first prescriptions dates of 11 bDMARDs and tsDMARDs (N = 672) and 3 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (N = 720) were analysed among 696 patients. TNF-alpha inhibitors accounted for the largest proportion of bDMARDs and tsDMARDs, comprising 79.3%. The prescription of bDMARDs and tsDMARDs increased, from a relative proportion of 32.2% in 2012 to 62.7% in 2023, while the prescription of csDMARDs declined from 67.8% in 2012 to 34.3% in 2023. The prescription of JAK inhibitors rose from 1.6% in 2020 to 5.9% in 2023.

Conclusions: This study provides a comprehensive overview of the implementation of targeted therapies (bDMARDs and tsDMARDs) in non-systemic JIA over the past decade, showing a rise in targeted therapies alongside a decrease in csDMARD prescriptions. While TNF-alpha inhibitors remain the most commonly prescribed, there has been a significant rise in the prescription of JAK inhibitors and other new therapies. Factors such as route of administration, patient comfort, costs and treatment efficacy may influence the adoption of these DMARDs. The findings highlight the need for continued research to identify factors for successful implementation of these therapies in clinical practice.

Autoinflammatory diseases, characterized by recurrent systemic inflammation due to innate immune dysregulation, often present with fever, arthritis, abdominal pain, and cutaneous involvement, with elevated acute-phase reactants during flare-ups. These rare conditions, arising from monogenic mutations or environmental triggers, can be challenging to diagnose, yet accurate identification is critical for effective targeted therapy. In 2022, Kanderova et al. reported a heterozygous c.1545C>A (p.Tyr515Ter) HCK gene mutation causing early-onset cutaneous pulmonary vasculitis due to increased kinase activity from a truncated HCK protein, leading to chronic inflammation and fatal progression despite partial suppression with ruxolitinib. HCK, a SRC family tyrosine kinase predominantly expressed in granulocytic and monocytic cells, regulates immune functions like phagocytosis and cytokine production. We report a 6-year-old female patient with recurrent fevers, cutaneous petechial rashes, chronic cough, exertional dyspnea, and persistent symptoms despite multiple antibiotic treatments for suspected recurrent lower respiratory tract infections since age  1.5 years, treated for presumed recurrent lower respiratory tract infections with multiple antibiotic courses, though symptoms persisted. No cutaneous manifestations were observed during the current admission, but elevated acute-phase reactants and pulmonary findings were noted. Based on clinical and laboratory features, a rare autoinflammatory condition was suspected. No pathogenic variants were identified in an autoinflammatory disease gene panel. Whole-exome sequencing (WES) using next-generation sequencing (NGS) revealed a novel splice site mutation (c.1016-5T>C) in the HCK gene, absent from existing genomic databases. Anti-IL1B targeted therapy achieved complete clinical and laboratory remission. This study identifies a novel HCK gene mutation as the cause of a hereditary autoinflammatory disease with early-onset pulmonary and cutaneous manifestations, consistent with classical autoinflammatory syndromes.

Background: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition that frequently persists into adulthood, posing long-term challenges in disease control and quality of life. However, clinical management during the transitional and young adult phases remains insufficiently characterized, especially in comparison with adult-onset rheumatoid arthritis (RA). This study aimed to compare disease activity, medication use, and treatment practices between patients with oligoarticular/polyarticular JIA and those with RA, focusing on individuals aged 16-30 years.

Methods: Data were derived from two nationwide multicenter databases in Japan-NinJa (National Database of Rheumatic Diseases in Japan) for RA and CoNinJa (a pediatric counterpart of NinJa) for JIA. A total of 176 JIA and 152 RA patients, all aged 16-30 years, were analyzed. Clinical parameters, disease activity indices, and medication profiles were compared using the Mann-Whitney U test and Fisher's exact test.

Results: Compared to RA patients, JIA patients demonstrated significantly lower disease activity (median SDAI 0.6 vs. 2.4) and higher remission rates, particularly Boolean remission (70% vs. 44%) (p < 0.001). MTX usage was less frequent in JIA (49% vs. 68%, p < 0.001), whereas biologic use was notably more common (69% vs. 38%, p < 0.001), with 31% involving off-label prescriptions. Among patients in CDAI remission, biologic monotherapy was observed more frequently in JIA (29% vs. 7%, p < 0.001). Discontinuation of MTX was most commonly attributed to disease improvement (58%) or gastrointestinal intolerance (nausea, 29%). Subcutaneous tocilizumab, though unapproved for JIA in Japan, had the lowest discontinuation rate (4%), suggesting favorable tolerability.

Conclusions: Despite an overlap in age, patients with JIA and RA exhibit distinct disease characteristics and therapeutic patterns. These differences underscore the need to expand approved treatment options for JIA, promote equitable access to biologics, and strengthen transitional care frameworks. Further research is warranted to explore long-term outcomes, reproductive health considerations, and socioeconomic barriers that influence treatment continuity in young adults with childhood-onset arthritis.