Programmed Cell Death Protein-1 Upregulation in Response to SARS-CoV-2 in Juvenile Idiopathic Arthritis: A Case-Control Study.

Currently, data regarding the impact of COVID-19 disease (caused by SARS-CoV-2) on patients with childhood rheumatic diseases are significantly limited. To assess the possible connection, we measured levels of IgA and IgG anti-SARS-CoV-2 antibodies in children with juvenile idiopathic arthritis (JIA) and a control group during the pandemic, prior to the introduction of anti-COVID-19 vaccination. We assessed levels of PD-1 suppressive molecule and inflammatory markers in patients and correlated those results with serological response to SARS-CoV-2. In JIA patients, the activity of the disease was assessed using the Juvenile Arthritis Disease Activity Score 71 (JADAS 71) scale. The study consisted of 96 children, 65 diagnosed with JIA, treated with antirheumatic drugs, and 31 healthy volunteers. In patients with JIA, significantly higher levels of SARS-CoV-2 antibodies in the IgA and IgG were demonstrated compared to the control group. We also found significantly higher serum PD-1 levels in JIA patients and control volunteers who were seropositive for SARS-CoV-2 IgA or IgG antibodies compared to those who were seronegative. The humoral immune response to SARS-CoV-2 infection is associated with the persistent upregulation of PD-1 expression in both JIA patients and healthy children. The clinical significance of the detected disorder requires further careful observation.

Vitamin D Profile and Disease Activity of Juvenile Idiopathic Arthritis (JIA) During Pandemic Covid-19

Vitamin D (25-Hydroxyvitamin D3 [25(OH)D3]) has an important role in the immune system. This study aimed to assess the relationship between 25-Hydroxyvitamin D3 and disease activity in Indonesian children with Juvenile Idiopathic Arthritis (JIA) during pandemic Covid-19. A 12-week randomized control trial was undertaken at Saiful Anwar Hospital between June and September 2021. JIA patients are divided into two groups. The control group (CG), without supplementation, and the treatment group (TG) got a high dose of oral cholecalciferol 2000 IU/day. Serum levels of 25(OH)D3 were measured using an enzyme-linked immunosorbent assay (ELISA). Comparison between serum 25(OH)D3 levels and JIA subtypes, peripheral blood Creactive protein (CRP), erythrocyte sedimentation rate (ESR), and Juvenile Arthritis Disease Activity Score (JADAS-27 Score) were analyzed using SPSS. There was a significant increase in serum 25(OH)D3 levels in treatment group (mean: 27.38 ± 6.39 ng/ml vs 42.26 ± 10.95 ng/ml;P=0.000). The JADAS-27 score significantly decrease in treatment group (14.60 ± 4.04 vs 6.24 ± 1.96;p= 0.000). Serum 25(OH)D3 showed a significant correlation with the JADAS-27 score. The levels of 25(OH)D3 are significantly decreased in children with JIA. Decreased 25(OH)D3 levels may be associated with the etiopathogenesis of JIA. Vitamin D levels have correlations with disease activity. Adjunctive treatment of cholecalciferol improves the disease activity in JIA patients. © 2022, Brawijaya University. All rights reserved.

Reactivation of juvenile idiopathic arthritis associated uveitis with posterior segment manifestations following anti-SARS-CoV-2 vaccination.

BACKGROUND/PURPOSE: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in the pediatric population and anterior uveitis is its commonest extra-articular manifestation. Typically the uveitis presents as chronic anterior uveitis and there is limited literature of the posterior segment manifestations of the disease. Similar to other vaccines, anti-SARS-CoV-2 vaccination that began as an urgent measure to control the spread of the SARS-CoV-2 pandemic has not been without adverse events. We are reporting a 19-year-old Asian Indian female who was diagnosed and treated for JIA associated anterior uveitis that was unilateral and was under anti-inflammatory control but showed worsening of uveitis with posterior segment inflammation in both eyes following anti-SARS-CoV-2 vaccination. CASE REPORT: A 19-year-old Asian Indian female with a history of juvenile idiopathic arthritis on treatment with methotrexate, presented with right eye chronic anterior uveitis with peripheral subclinical retinal vasculitis and macular edema which was brought under control following administration of adalimumab. She was inflammation free for 6 months until she received anti-SARS-CoV-2 vaccination and developed new onset floaters in both eyes that were initially noted after the first dose and increased after the second dose. Clinical examination revealed presence of keratic precipitates and grade 1+ anterior chamber inflammation along with vitiritis in both eyes. Fundus fluorescein angiography revealed angiographically active retinal vasculitis without the presence of macular edema in both eyes. This was managed with a short course of topical difluprednate and continuation of systemic immunosuppressive therapy with adalimumab and methotrexate. CONCLUSION: JIA associated uveitis results from an autoimmune process which can be controlled with timely immunosuppressive treatment. It is important to be aware of the potential risk of flare up of uveitis with posterior segment manifestations following anti- SARS-CoV-2 vaccination.

Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in adolescents with rheumatic diseases treated with immunomodulatory medications.

OBJECTIVES: Adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRDs) could be at risk for disease flare secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or to withholding anti-inflammatory therapy. While vaccination can protect against coronavirus disease 2019 (COVID-19), safety and immunogenicity data regarding anti-SARS-CoV-2 vaccines among adolescents with AIIRDs are limited. This international, prospective, multicentre study evaluated the safety and immunogenicity of the BNT162b2 anti-SARS-CoV-2 vaccine among adolescents and young adults with juvenile-onset AIIRDs, 80% of whom are on chronic immunomodulatory therapy. METHODS: Vaccine side effects, disease activity and short-term efficacy were evaluated after 3 months in 91 patients. Anti-spike S1/S2 IgG antibody levels were evaluated in 37 patients and 22 controls 2-9 weeks after the second dose. RESULTS: A total of 91 patients and 40 healthy controls were included. The safety profile was good, with 96.7% (n = 88) of patients reporting mild or no side effects and no change in disease activity. However, three patients had transient acute symptoms: two following the first vaccination (renal failure and pulmonary haemorrhage) and one following the second dose (mild lupus flare vs viral infection). The seropositivity rate was 97.3% in the AIIRD group compared with 100% among controls. However, anti-S1/S2 antibody titres were significantly lower in the AIIRD group compared with controls [242 (s.d. 136.4) vs 387.8 (57.3) BAU/ml, respectively; P < 0.0001]. No cases of COVID-19 were documented during the 3 month follow-up. CONCLUSION: Vaccination of juvenile-onset AIIRD patients demonstrated good short-term safety and efficacy and a high seropositivity rate but lower anti-S1/S2 antibody titres compared with healthy controls. These results should encourage vaccination of adolescents with juvenile-onset AIIRDs, even while on immunomodulation.

Impact of the COVID-19 pandemic on juvenile idiopathic arthritis presentation and research recruitment: results from the CAPRI registry.

OBJECTIVE: The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada. METHODS: Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively. RESULTS: The median time from symptom onset to first assessment was 138 (IQR 64-365) days pre-pandemic vs 146 (IQR 83-359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020. CONCLUSIONS: We did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved.

Macrophage Activation Syndrome in a Child with Juvenile Idiopathic Arthritis Secondary to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic affecting many countries and millions of people. Physicians have encountered some rare and challenging cases related to SARS-CoV-2, a novel virus with still many unknowns. In order to share our experience of a such clinical picture, we present here a child with SARS-CoV-2-induced macrophage activation syndrome in the setting of juvenile idiopathic arthritis.

Management of Juvenile idiopathic arthritis-associated uveitis duringthe COVID-19 pandemic in a pediatric referral center in Lombardy.

Italy was the first European country to be affected by the SARS-CoV-2 pandemic. In this scenario, we had to face a new clinical approach in our Pediatric Rheumatology Unit for the management of patients affected by juvenile idiopathic arthritis (JIA)-associated uveitis. During the lockdown (phase 1), the weekly outpatient clinic was discontinued and telephone consultations were set up. A toll-free telephone number was instituted for emergencies. None of our children with JIA-associated uveitis was advised to stop the ongoing immunosuppressant systemic therapy. We had no cases of COVID-19 infection and uveitis activity was under control in all but two out of 125 patients, which was comparable with the pre-COVID-19 situation. During phase 2 of the pandemic, hospital and ambulatory rearrangements were made to minimize the risk of SARS-CoV-2 infection. Overall, during the first 4 weeks of phase 2, we did not notice an increased number of patients with uveitis activity.