Pediatric Rheumatology最新文献

Objectives: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease with highly heterogenous clinical manifestations and severity. Herpes zoster (HZ) is a viral disease caused by reactivation of varicella-zoster virus which remains dormant in the dorsal root sensory ganglia after a previous varicella infection. There is limited information on the association between HZ and childhood-onset SLE (cSLE). This study aimed to determine the risk factors for HZ in patients diagnosed with cSLE.

Patients and methods: Single-center retrospective cohort study which included all patients less than 19 years old with SLE at a tertiary hospital in the Philippines.

Results: A total of 388 patients were included in the study. The prevalence of HZ was 15.72%, with an incidence rate of 38.40 per 100 person-years. The most common location of the HZ was the upper extremities (18.03%). The median SLEDAI at HZ diagnosis was 4, 16.39% had recurrent HZ, 11.48% had superimposed bacterial infection, and more than two-thirds were treated with acyclovir or valacyclovir (88.52%). The proportion of participants with renal manifestations was significantly higher among those with HZ (54.10% vs. 40.37%). Glucocorticoid dosage ≥ 5 mg, azathioprine, and intravenous cyclophosphamide significantly predict the likelihood of developing HZ. In particular, IV cyclophosphamide, azathioprine, and glucocorticoid doses of ≥ 5 mg increased the risk for the development of HZ by 1.61 (p = 0.048), 2.07 (p = 0.009), and 10.20 (p = 0.001) times, respectively.

Conclusion: The prevalence and incidence of HZ in cSLE patients are 15.72% and 38.40 per 100 person-years, respectively. The risk factors identified for HZ among cSLE patients were lymphopenia, lupus nephritis, and immunosuppressive agents. Glucocorticoid dosage ≥ 5 mg, azathioprine, and intravenous cyclophosphamide significantly predict the likelihood of developing HZ.

Since the molecular characterization of periodic fever syndromes led to the concept of autoinflammation, the pace of scientific advancement in this field has been dramatic. Here, we review many of the most impactful new discoveries in autoinflammation, as presented at the 2024 Pediatric Rheumatology European Society Congress. This includes new genes and diseases, such as SHARPIN mutations and dominant-negative mutations in OTULIN as causes of disorders of ubiquitination, PMVK mutations as potential causes of a mevalonate kinase deficiency mimic, and ARF1 and REXO2 as causes of interferonopathy. Several new molecular mechanisms and mutations were also reported for older diseases including coatomer protein complex subunit alpha (COPA) syndrome, Aicardi-Goutières syndrome, PLCG2-associated immune dysregulation (PLAID), and NLRP3-AID. Finally, molecular and omics studies of STING1-associated vasculopathy with onset in infancy (SAVI) and haploinsufficiency of A20 (HA20) contributed to advances in underlying autoinflammatory biology.

Background: Takayasu arteritis (TA) is a granulomatous inflammatory disease of unknown etiology that affects the aorta and its branches, including the coronary and pulmonary arteries. Diagnosis in pediatric age is late because the initial manifestations are nonspecific.

Methods: Objective: Describe demographic, epidemiological, clinical characteristics, aortic and cardiovascular damage of patients with TA in pediatric age, and status in adult life. Retrospective study between 1988 and 2023. All children met the EULAR/PRINTO/PRES criteria for pediatric TAK. The records of symptom onset, type of angiographic lesion, surgical or interventional procedures, evolution, and status were reviewed.

Results: The median was 12 years, with Q1-Q3 (8-15). Predominant symptoms were fatigue 29%, angina in 12%, Arterial hypertension in 53%, congestive heart failure in 12%, and stroke in 12%. The most common angiographic classification of Hata was type V, associated with a pulmonary artery lesion (V + P) in 6 (12%) and a coronary artery lesion (V + C) in 4 (8%). Forty-one patients (84%) reached adulthood; 5 (10%) discontinued care in childhood, so their prognosis is unknown.

Conclusion: The timely identification of TA in children is a challenge that requires clinical art. Timely medical and interventional management allows a better prognosis and long-term survival.

Background: Systemic juvenile idiopathic arthritis (SJIA) is a severe form of juvenile idiopathic arthritis characterized by fever, rash, chronic arthritis, and systemic inflammation. The introduction of biologics has improved the treatment options for SJIA. Canakinumab selectively inhibits interleukin-1β and is approved for SJIA treatment. In this study that utilized the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, long-term safety data available from patients with SJIA who started either canakinumab treatment or an alternative therapy were assessed.

Methods: This long-term, prospective, non-interventional study was conducted from August 2015 to June 2022 using data from the CARRA Registry. Data for serious adverse events (SAEs) and pre-specified events of special interest (ESIs) were collected from patients with SJIA aged between ≥ 2 and < 18 years at the time of treatment initiation and followed for a minimum of 5 years. Data were summarized descriptively, and no hypothesis testing was performed.

Results: The final analysis included 177 patients: 90 in the overall canakinumab group (incident users [N = 39] and prevalent users [N = 51]) and 87 in the alternative treatment group. Median patient age at treatment initiation was 8.0 years in the overall canakinumab group. The incidence rates of SAEs per 100 patient-years were 3.62 (overall canakinumab group) and 3.39 (canakinumab incident users group). Of the predefined ESIs, macrophage activation syndrome (n = 5) and infections treated with intravenous anti-infectives (n = 1) were observed in the overall canakinumab group. The majority of patients (72.2%) treated with canakinumab received on-label dosing at some point during the first 5 years of the study.

Conclusions: Overall, no changes were observed in the safety profile with long-term use of canakinumab in pediatric patients with SJIA. Particularly, no change in the frequency or severity of known ESIs occurred, and no new risks were identified. The findings suggest that canakinumab is effective in SJIA management and has a favorable safety profile with long-term use over a period of 5 years in real-world settings.

Background: Immunoglobulin A vasculitis (IgAV) is the most common childhood vasculitis and can lead to immunoglobulin A vasculitis nephritis (IgAVN) in severe cases, potentially progressing to kidney failure in a subset of children. Safer and more effective treatments are needed to improve outcomes in these children. This study aimed to evaluate the efficacy and safety of telitacicept in the treatment of children with IgAV and IgAVN.

Methods: This is a single-center, retrospective observational study of twenty four children with IgAV or IgAVN who received telitacicept treatment, and thirty matched children with IgAVN who only received conventional treatment were taken as the control group for children with IgAVN who received telitacicept treatment in acute phase. The treatment response was evaluated through urine protein, serum albumin, eGFR and serum immunoglobulin levels, and data was analyzed at telitacicept initiation and at 4, 12, 24 and 36 weeks after treatment.

Results: A total of twenty four children (thirteen boys and eleven girls) with IgAV (n = 5) and IgAVN (n = 19, comprising ten acute and nine chronic cases) were enrolled. All children with IgAV experienced improvement of skin, joint, and gastrointestinal symptoms after telitacicept treatment, with no kidney involvement during follow-up. In children with IgAVN, the urinary protein-to-creatinine ratio (UPCR) significantly decreased at 36 weeks compared to baseline (P < 0.05) in both acute and chronic groups, while estimated glomerular filtration rate (eGFR) remained stable (P > 0.05). In addition, the dose of steroids administered during the treatment with telitacicept was significantly reduced, the acute IgAVN group exhibited significantly greater steroid reduction between weeks 4 and 24 compared with the controls group (P < 0.05). Furthermore, serum immunoglobulin levels (IgA, IgG) significantly decreased 12 weeks after telitacicept treatment (P < 0.01), and no other adverse reactions observed.

Conclusion: Telitacicept appears to be a promising therapy for children with IgAV and IgAVN, effectively inducing proteinuria remission, improving systemic symptoms, and reducing the use of steroids, with favorable safety.

Background: Children with rheumatic diseases are at risk for contracting severe influenza and COVID-19 and are thus targeted for these vaccination.

Objectives: To assess the influenza (flu) vaccination rate in children with Juvenile Idiopathic Arthritis (JIA), investigate families' attitudes towards the influenza vaccine, and the effect of the COVID-19 pandemic on flu vaccine uptake.

Methods: This multi-centre, cross-sectional study was conducted across 9 countries. JIA caregivers completed an anonymous questionnaire about their children's influenza vaccination, including the 2019-2020 and 2020-2021 seasons, including knowledge, and perceptions regarding influenza vaccination.

Results: Based on responses from 655 JIA caregivers, 152 children (23.2%) received influenza vaccinations in the 2020-2021 season, representing a significant rise from 18.6% in the previous season (p < 0.01). The likelihood of vaccination was higher among employed/self-employed caregivers compared to unemployed (28.2% and 29.9% vs. 13.9%), and those with tertiary education versus elementary (28% vs. 9.7%), both p < 0.01. Concerns of children's vulnerability to SARS-CoV-2 and severe COVID-19 disease due to JIA were prevalent (51.3% and 85.3% respectively), with 51.3% supporting COVID-19 vaccination. Caregivers who previously vaccinated their children for influenza showed a greater inclination towards SARS-CoV-2 vaccination (73.4% and 79.5%, p < 0.01).

Conclusions: Families of children with JIA reported an increasing flu vaccine uptake and a high intention for COVID-19 vaccine administration. Previous vaccination behavior was shown as a significant predictor of future behaviour. Strengthening health education may address fears and lead to better vaccine coverage against both influenza and SARS-CoV-2 in children with JIA and other inflammatory rheumatic diseases.

Background: Juvenile dermatomyositis (JDM) is an inflammatory vasculopathy characterized by muscle weakness and systemic inflammation. This study aimed to investigate the clinical utility of neutrophil activation markers, specifically calprotectin (S100A8/A9) and myeloperoxidase (MPO)-DNA complexes, as potential biomarkers for muscle inflammation and predictors of muscle outcomes in JDM.

Findings: Plasma levels of calprotectin and MPO-DNA were quantified using ELISA in JDM (n = 36), juvenile idiopathic arthritis (JIA, n = 13), and healthy controls (HCs, n = 21). Disease severity and muscle function were assessed using the Childhood Myositis Assessment Scale (CMAS), Physician Global Assessment (PGA), and Manual Muscle Testing 8 (MMT8). JDM patients exhibited significantly higher plasma calprotectin and MPO-DNA levels as compared to HCs (p = 0.0008 and p = 0.0048, respectively). Calprotectin levels correlated with muscle function scores (CMAS r=-0.682, p = 0.0002; MMT8 r=-0.59, p = 0.005; and PGA muscle scores r = 0.452, p = 0.014). Patients with elevated levels of both calprotectin and MPO-DNA tended to have greater disease activity and muscle involvement. Exploratory ROC analysis suggested that baseline calprotectin and MPO-DNA levels may help distinguish active disease. Notably, higher baseline levels of these markers correlated with improved MMT8 scores over time (r = 0.634, p = 0.027; r = 0.582, p = 0.047), suggesting an association with greater subsequent improvement in muscle strength.

Conclusions: These findings highlight calprotectin and MPO-DNA as potential biomarkers for JDM muscle inflammation and functional outcomes. These results suggest that neutrophil activation plays a key role in JDM pathogenesis and may provide insights into disease monitoring and treatment strategies.