Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

Secukinumab Therapy in Refractory Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatologic condition in childhood, remains a cause of significant morbidity, particularly in those with spondyloarthropathy, including psoriatic arthritis (PsA) and enthesitis-related arthritis (ERA). While secukinumab was recently approved for the treatment of children and adolescents with ERA and PsA, there is limited published data on its use in JIA, particularly in refractory cases, despite its efficacy in the treatment of adult arthritis. We aim to examine the use of this therapy in JIA in a single pediatric rheumatology center. A retrospective chart review was performed and 10 JIA patients who received treatment with secukinumab were identified. Data extracted included disease activity, patient demographics, comorbidities, medications, and laboratory data. Seven ERA, 2 PsA, and 1 poly JIA patient were treated with secukinumab at our center between April 2011 and July 2021. These patients had notably resistant disease, with a mean disease-modifying antirheumatic drug (DMARD) failure rate of 3.8. One hundred percent of patients who underwent magnetic resonance imaging (MRI) after being on at least 3 months of secukinumab therapy demonstrated improvement in their MRI findings. One patient developed a flare of uveitis while on secukinumab therapy, with no other adverse events recorded in our patients. Secukinumab therapy was recently approved for children and adolescents with ERA and PsA, and may offer an efficacious option given its demonstrated improvement in imaging and joint examination, as well as qualitative reports of pain, even in those who have failed other therapies. However, caution may be warranted in those with a history of uveitis and warrants further study.

COVID-19 after rituximab therapy in cSLE patients.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease associated with significant morbidity and mortality. Rituximab is a B-cell depleting therapy utilized in the treatment of SLE. In adults, rituximab has been associated with increased risk of adverse outcomes in patients who develop coronavirus disease 2019 (COVID-19). We aimed to assess the impact of prior rituximab treatment on clinical outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children with SLE. To describe the impact of rituximab on outcomes from SARS-CoV-2 infection, we conducted a retrospective study of pediatric SLE patients in our center diagnosed with COVID-19 who had previously received rituximab between February 2019 and October 2022. Patients' clinical characteristics, disease activity, and outcomes were assessed. Of the eight subjects assessed, five required hospitalizations for COVID-19, four required ICU admission, and two were seen in the emergency department for their symptoms. One patient ultimately expired from her illness. The median time between rituximab administration and COVID-19 diagnosis was 3 months. We assessed the clinical outcomes, including the need of ICU admission and fatal outcome, of COVID-19 in our cSLE patient population after rituximab administration. Approximately 60% of our patients required hospitalization for their illness, and seven out of eight patients required healthcare utilization to include hospitalization and/or emergency department visits.

Multiple MIS-C Readmissions and Giant Coronary Aneurysm After COVID-19 Illness and Vaccination: A Case Report.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) rarely involves delayed giant coronary aneurysms, multiple readmissions or occurrence after COVID-19 vaccination. METHODS: We describe a child with all 3 of these unusual features. We discuss his clinical presentation, medical management, review of the current literature and CDC guidance recommendations regarding further vaccinations. RESULTS: A 5-year-old boy had onset of MIS-C symptoms 55 days after COVID-19 illness and 15 days after receiving his first BNT162b2 COVID-19 vaccination. He was admitted 3 times for MIS-C, and twice after his steroid dose was tapered. On his initial admission, he was given intravenous immunoglobulin and steroids. During his second admission, new, moderate coronary dilation was noted, and he was treated with intravenous immunoglobulin and steroids. At his last admission, worsening coronary dilation was noted, and he was treated with infliximab and steroids. During follow-up, he had improvement in his coronary artery dilatation. However, his inflammatory markers increased after steroid wean, and his steroid taper was further extended, after which time his inflammatory markers improved. This is the only such reported case of a patient who was admitted 3 times for MIS-C complications after COVID-19 vaccination. CONCLUSION: MIS-C rarely involves delayed giant coronary aneurysms, multiple readmissions, or occurrence after COVID-19 vaccination. Whether our patient's COVID-19 vaccine 6 weeks after COVID-19 illness contributed to his MIS-C is unknown. After consultation with the CDC-funded Clinical Immunization Safety Assessment Project, the patient's care team decided against further COVID-19 vaccination until at least 3 months post normalization of inflammatory markers.

Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities. To further assess whether the degree of SF neutrophilia associated with altered immune responses in JIA, we collected SF and blood from 16 adolescent JIA patients. SF and blood leukocytes were analyzed by flow cytometry. SF and plasma were used for immune mediator quantification and metabolomics. Healthy donor blood T cells were cultured in SF to evaluate its immunoregulatory activities. PMN and T cell frequencies were bimodal in JIA SF, delineating PMN high/T cell low (PMNHigh) and PMN low/T cell high (PMNLow) samples. Proinflammatory mediators were increased in SF compared with plasma across patients, and pro- and anti-inflammatory mediators were further elevated in PMNHigh SF. Compared to blood, SF PMNs showed increased exocytosis and programmed death-1/programmed death ligand-1 expression, and SF PMNs and monocytes/macrophages had increased surface-bound arginase-1. SPADE analysis revealed SF monocyte/macrophage subpopulations coexpressing programmed death-1 and programmed death ligand-1, with higher expression in PMNHigh SF. Healthy donor T cells showed reduced coreceptor expression when stimulated in PMNHigh versus PMNLow SF. However, amino acid metabolites related to the arginase-1 and IDO-1 pathways did not differ between the two groups. Hence, PMN predominance in the SF of a subset of JIA patients is associated with elevated immune mediator concentration and may alter SF monocyte/macrophage phenotype and T cell activation, without altering immunoregulatory amino acids.

Pediatric psoriatic arthritis: a population-based cohort study of risk factors for onset and subsequent risk of inflammatory comorbidities.

BACKGROUND: Relatively little is known about the epidemiology of juvenile psoriatic arthritis (PsA), including clinical features associated with the development of arthritis among children with psoriasis and subsequent risk of inflammatory comorbidities. OBJECTIVE: To identify the overall risk of arthritis among children with psoriasis and subsequent risk of inflammatory comorbidities. METHODS: Using Clinformatics™ DataMart (OptumInsight, Eden Prairie, MN) de-identified US administrative claims data from 2000-2013, we identified children 0-16 years with an incident diagnosis of psoriasis or PsA using ICD-9-CM diagnostic, procedure and pharmacy billing codes. Cox proportional hazard regression was performed to assess clinical features associated with development of arthritis in children with psoriasis. Incidence rate ratios were used to compare the relative frequency of co-morbid diagnoses. RESULTS: We identified 212 children with PsA, 4,312 with psoriasis-only, and 45,240 controls. Approximately 33% of children with PsA received a diagnostic code for psoriasis before arthritis. Median time to index code for arthritis after index code for psoriasis was 17.6 months (IQR 4.1-38.1). Older age and uveitis were associated with a significantly increased risk of developing arthritis in children with psoriasis. Children with PsA had a significantly increased risk of uveitis, diabetes, and depressive disorder when compared to patients with psoriasis and inflammatory bowel disease, uveitis, diabetes, and depressive disorder when compared to controls. CONCLUSION: Most children with PsA developed arthritis first. Older age and uveitis were risk factors for arthritis among children with psoriasis. PsA was associated with increased risk of several clinically relevant inflammatory comorbidities.

Obesity and Pediatric Psoriatic Arthritis.

OBJECTIVE: Studies in adults have shown a significant association between obesity and psoriatic arthritis, however the association of obesity with pediatric psoriatic arthritis is unknown. We aimed to evaluate obesity in pediatric psoriatic arthritis. METHODS: We conducted a cross-sectional study of children with psoriasis and psoriatic arthritis evaluated at a single center between 6/2010 and 9/2014. Two healthy reference populations were utilized: 1) local reference population from the surrounding community and 2) a national reference population derived from NHANES. Age and sex-specific z-scores for weight, height, and body mass index (BMI) were calculated. Differences in clinical and demographic characteristics between groups were assessed. RESULTS: During the study period, 48 children with psoriatic arthritis and 231 patients with psoriasis were evaluated. Three (6.2%) and 5 (10.4%) of the children with psoriatic arthritis were overweight or obese, respectively. In comparison to the reference healthy groups and psoriasis patients, the mean BMI z-score of children with psoriatic arthritis was not statistically different. However, patients with psoriasis were more likely to be obese than the community reference population (p-value <0.001). CONCLUSIONS: Children with psoriasis were more obese than the healthy reference population, however there was no statistically significant difference in obesity between children with psoriatic arthritis and psoriasis or psoriatic arthritis and the reference population. This lack of association may be reflective of true differences in pediatric and adult-onset disease and warrants further investigation.