Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure: Respiratory syncytial virus. Main Outcomes and Measures: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: Evidence regarding effectiveness of interleukin-1 receptor antagonism in multisystem inflammatory syndrome in children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. METHODS: We conducted a retrospective cohort study of MIS-C cases in a US surveillance registry from November 2020 to December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0-1) were identified. We compared cases in patients ages 2-20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids versus anakinra plus IVIG and/or glucocorticoids on days 0-1, using inverse probability weighting to balance disease severity. Primary outcomes were vasopressor requirement on day 3 and impaired left ventricular ejection fraction on days 3-4. The secondary outcome was 50% reduction in C-reactive protein on day 3. RESULTS: Among 1,516 MIS-C cases at 44 sites, 193 (13%) patients received anakinra alone or with other immunomodulators as initial treatment (range 0-74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing disease severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (n = 121) versus IVIG plus glucocorticoids (n = 389) was not associated with significant differences in vasopressor requirement (25.6% versus 20.1%, respectively; risk ratio [RR] 1.27 [95% confidence interval (95% CI) 0.88-1.84]), ventricular dysfunction (33.7% versus 25.7%, respectively; RR 1.31 [95% CI 0.98-1.75]), or C-reactive protein reduction. CONCLUSION: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020.

Importance: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. Objective: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. Design, Setting, and Participants: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). Results: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. Conclusions and Relevance: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.

Bell's palsy with facial bone involvement: A rare presentation of chronic nonbacterial osteomyelitis with literature review.

Chronic nonbacterial osteomyelitis (CNO) is a chronic, sterile, inflammatory disease. It primarily presents with nonspecific bone pain and swelling but ultimately can cause bone destruction and deformities, if left untreated. The involvement of the cranial bones (apart from the mandible) is rare in CNO. In this report, we present a rare case of CNO affecting facial and cranial bones presenting as facial palsy with a review of the literature about similar affection. A 10-year-old, previously healthy female was initially evaluated for swelling of the left side of her face with slight tenderness on palpation, but no fever. Her complete blood count was unremarkable, her inflammatory markers were elevated (C-reactive protein 7.5 mg/dl and erythrocyte sedimentation rate 104 mm/h), and CT of facial and skull bones and MRI of brain showed a destructive osseous process involving the left maxillary, zygomatic, sphenoid bones and the clivus. Bone biopsy of the left maxilla showed fibrous dysplasia with abscess formation, most consistent with an infectious aetiology (acute osteomyelitis). She was started on oral clindamycin for a 3-month course. The facial swelling improved after starting clindamycin, but on her sixth week of treatment, she developed right-sided Bell's palsy. An MRI of the brain showed hyperenhancement of the right seventh cranial nerve. A month later, she was evaluated for right wrist and knee swelling, pain, and limitation of movement. Skeletal survey and MRI showed multifocal lesions with mixed sclerosis and lucency. Her inflammatory markers continued to be elevated. Another bone biopsy of the right radius showed similar findings of destruction with no evidence of malignancy. She was ultimately diagnosed with CNO. She was started on nonsteroidal anti-inflammatory drugs with gastric protection and regular follow-up. Over more than a year of follow-up, the patient's inflammatory markers remain normal, and joint swelling/limitation has remained in remission. We found five additional cases in the literature that presented with a similar presentation. To our knowledge, our patient is the first reported case in the USA involving the cranial/facial bones apart from the mandible presenting with facial palsy. The affection of the facial bones (apart from the mandible) in CNO is very rare, but the awareness of such a presentation by the clinician is an important aspect of reaching the diagnosis.

Establishing core domain sets for Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO): A report from the OMERACT 2020 special interest group.

OBJECTIVE: A working group was established to develop a core domain set (CDS) for Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) following the OMERACT filter 2.1. METHODS: A scoping review to identify disease-related manifestations was performed, followed by a special interest group (SIG) session at OMERACT2020 to begin the CNO/SAPHO CDS framework. RESULTS: Candidate items were identified from the scoping review and most fell under Life Impact and Pathophysiology Manifestation core areas. A SIG agreed on the need to develop a CDS for CNO and SAPHO (100%) and for children and adults (91%). CONCLUSION: Based on candidate items identified, qualitative research and Delphi surveys will be performed as next steps.

Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series.

Juvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5-27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8-7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.

Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.

Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen ß2-glycoprotein I (ß2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-ß2GPI IgG autoantibodies. R. int immunization of mice induced ß2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human ß2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease.

Pediatric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses associated with persistently positive antiphospholipid antibodies. There is currently a paucity of data (incidence, prevalence, thrombosis risk, and effective treatment) in pediatric APS. The purpose of this report is to review the current literature on APS in children and neonates, identify the gaps in current knowledge, and suggest avenues for studies to fill those gaps.

Anaphylaxis to anakinra in a pediatric patient with systemic juvenile idiopathic arthritis successfully treated with canakinumab: a case-based review.

We present the case of a 2-year-old boy with a history of necrotizing enterocolitis (NEC) with ileostomy diagnosed with systemic juvenile idiopathic arthritis (sJIA) at 10 months of age controlled on anti-interleukin-1 (anti-IL-1) therapy (anakinra). At 17 months of age, ileostomy reversal and bowel re-anastomosis was scheduled with anakinra discontinued 3 days prior to the surgery and steroids initiated in its place. Ten days postoperatively, anakinra was re-started for signs of sJIA flare. Three months later, he developed persistent peripheral eosinophilia and subsequent anaphylactic reaction 6 months postoperatively. The patient safely tolerated an alternative anti-IL-1 agent (canakinumab). Anaphylaxis to anakinra has not been previously reported in the pediatric literature. This case highlights an important issue in a pediatric patient with sJIA: safety of an alternate anti-IL-1 agent, following development of allergy to one initial agent.

14th International Congress on Antiphospholipid Antibodies: task force report on antiphospholipid syndrome treatment trends.

Antiphospholipid Syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity occurring in patients with persistent antiphospholipid antibodies (aPL). The primary objective of the APS Treatment Trends Task Force, created as part of the 14th International Congress on aPL, was to systematically review the potential future treatment strategies for aPL-positive patients. The task force chose as future clinical research directions: a) determining the necessity for controlled clinical trials in venous thromboembolism with the new oral direct thrombin or anti-factor Xa inhibitors pending the results of the ongoing rivaroxaban in APS (RAPS) trial, and designing controlled clinical trials in other forms of thrombotic APS; b) systematically analyzing the literature as well as aPL/APS registries, and creating specific registries for non-warfarin/heparin anticoagulants; c) increasing recruitment for an ongoing primary thrombosis prevention trial, and designing secondary thrombosis and pregnancy morbidity prevention trials with hydroxychloroquine; d) determining surrogate markers to select patients for statin trials; e) designing controlled studies with rituximab and other anti-B-cell agents; f) designing mechanistic and clinical studies with eculizumab and other complement inhibitors; and g) chemically modifying peptide therapy to improve the half-life and minimize immunogenicity. The report also includes recommendations for clinicians who consider using these agents in difficult-to-manage aPL-positive patients.

Catastrophic antiphospholipid syndrome: how to diagnose a rare but highly fatal disease.

Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses and/or pregnancy loss associated with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS (CAPS) is the most severe form of APS with multiple organ involvement developing over a short period of time, usually associated with microthrombosis. 'Definite' and 'probable' CAPS have been defined based on the preliminary classification criteria; however, in a real-world setting, aPL-positive patients with multiple organ thromboses and/or thrombotic microangiopathies exist who do not fulfill these criteria. Previous APS diagnosis and/or persistent clinically significant aPL positivity is of great importance for the CAPS diagnosis; however, almost half of the patients who develop CAPS do not have a history of aPL positivity. The purpose of this paper is to summarize the diagnostic challenges and the recently updated diagnostic algorithms for CAPS providing a 'step-by-step' approach for clinicians (and researchers) in the assessment of patients with multiple organ thromboses.

Takayasu arteritis presenting in the context of active tuberculosis: a pediatric case.

Takayasu arteritis (TA) is a large-vessel vasculitis, most commonly presenting in young adults and more rarely in pediatric patients. An apparent association between TA and Mycobacterium tuberculosis has been noted previously, although this potential relationship is not yet understood. We present the case of a 16-year-old Haitian girl diagnosed with TA, originally presenting in the context of active tuberculosis. Our patient has been treated with antituberculosis therapy, corticosteroids, methotrexate, and rituximab to control her continued active vasculitis. With this case report, we seek to promote further exploration of the apparent association between TA and tuberculosis, as further clarification of the nature of this relationship may lead to the development of more targeted therapies and better outcomes for TA patients.