Pediatric Rheumatology最新文献

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.

Background: Canakinumab is a fully human monoclonal antibody that primarily targets interleukin-1β (IL-1β) and is primarily indicated for systemic juvenile idiopathic arthritis (sJIA). Since it is predominantly used in children aged 0-16 years, exploring its safety in real-world settings is of paramount importance.

Methods: This study evaluated the real-world safety of Canakinumab in clinical practice by analyzing adverse events (AEs) associated with the use of the drug in the 0-16 year age group with sJIA from 2014 to 2023, using data retrieved from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis of relevant AEs was performed via four methods: the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the multi-item gamma Poisson shrinker (MGPS), and the Bayesian confidence propagation neural network (BCPNN). Additionally, the Weibull shape parameter (WSP) test distribution was employed to model the risk of AEs over time.

Results: A total of 439 adverse events (AEs) were included in this study. Positive signals were identified for several adverse reactions listed on the drug label, including inappropriate schedule of product administration, incorrect dose administered, rash, illness, gastroenteritis, thrombocytopenia, lymphadenopathy, leukopenia, transaminases increased, aspartate aminotransferase increased and alanine aminotransferase increased. Furthermore, the study identified potential adverse reactions not mentioned on the label, such as hemophagocytic lymphohistiocytosis, COVID-19, nasal congestion and increased serum ferritin. These findings underscore the importance of AE monitoring, particularly emphasizing the value of early detection.

Conclusion: This FAERS-based pharmacovigilance study provides preliminary safety data on the use of Canakinumab in children aged 0-16 years with sJIA, confirming several known adverse reactions and revealing additional potential risks. These findings offer clinicians valuable safety information for the use of Canakinumab in the treatment of sJIA.

Background: Hemophagocytic lymphohistiocytosis (HLH) is an excessive immune activation syndrome. The genetic studies on every patient diagnosed with HLH recently became a standard of care. The likelihood of identifying a gene mutation is highest in the youngest patients.

Results: Four HLH patients had changes in the following five genes: NLRP1 (c·923 G > A), DOCK 8 (Dedicator of Cytokinesis 8) (c·3067A > G), AIRE gene (c·10 G > A) and one in the RNASEH2B (c·649T > C), PSTPIP1 (c·1213C > T). No mutations in genes previously associated with HLH syndrome were found.

Conclusions: The described cases show that genetic analysis is helpful for the diagnosis of HLH in pediatric patients. The functional analysis of a putative mutation is essential for understanding the pathological mechanism; while not every change in DNA might be responsible for the disease. Each patient might have different mutations; however, they all develop the same clinical outcome. Disruption at different levels can result in a similar picture.

Background: Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by a wide clinical variability among individuals, indicating that both genetic and environmental factors influence disease progression. Although the Mediterranean Diet (MD) is recognized for its anti-inflammatory properties, its relationship with FMF severity remains uninvestigated. This study aims to explore the association between MD adherence and FMF severity, while considering individuals' genetic background, lifestyle, and comorbid health conditions.

Methods: A cross-sectional survey was conducted among 101 confirmed individuals with FMF in Lebanon. Data were collected using a questionnaire that included participants' demographics, socio-economic status, disease manifestations, comorbidities, treatment, and lifestyle habits. FMF severity was determined using the International Severity Score for FMF (ISSF), dietary adherence was assessed using the Modified Mediterranean Prime Screen (MMPS), and physical activity was evaluated using the International Physical Activity Questionnaire-Short Form (IPAQ-SF).

Results: Adherence to the MD Score (MDS) was categorized as low (34%), moderate (48%), and high (19%). Most MD component intakes did not meet the recommended ranges. While no relationship was found between MD adherence and FMF severity, specific clinical manifestations, such as diarrhea, differed significantly, with a higher frequency noted in the low MD group. Obesity, high levels of physical activity, and the presence of comorbidities-particularly rheumatoid manifestations, inflammatory bowel disease, and cardiovascular diseases-were associated with a significant increase in FMF severity among participants; however, none of these factors emerged as independent predictors in multivariate models.

Conclusions: Our findings reinforce the multifactorial aspect of FMF and underscore the need for a comprehensive approach that addresses all contributing factors collectively.