Validation of childhood lupus specific targets: ensuring accurate assessment of disease control in younger, lighter paediatric patients.

Objectives: To validate novel childhood-onset systemic lupus erythematosus (cSLE) T2T targets including Childhood Lupus Low Disease Activity State (cLLDAS), cSLE Clinical Remission on steroids (cCR), and cSLE Clinical Remission off steroids (cCR-0), as compared with adult-onset SLE (aSLE) targets.

Methods: Attainment of the aforementioned cSLE-specific and aSLE-specific targets (LLDAS, DORIS 2021 Remission) was assessed at each visit, in UK JSLE Cohort Study patients. Univariable and multivariable Prentice-Williams-Peterson (PWP) gap-time models investigated the impact of target attainment on new damage and severe flare.

Contributors to Organ Damage in Childhood Lupus: Corticosteroid Use and Disease Activity.

Background: Awareness of paediatric-specific predictors of damage in Childhood-lupus is needed to inform mitigation measures.

Objectives: To ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods: Analysis included UK JSLE Cohort Study participants.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16.

Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus.

Objectives: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE).

Methods: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage.

A validation study of the identification of haemophagocytic lymphohistiocytosis in England using population-based health data.

We assessed the validity of coded healthcare data to identify cases of haemophagocytic lymphohistiocytosis (HLH). Hospital Episode Statistics (HES) identified 127 cases within five hospital Trusts 2013-2018 using ICD-10 codes D76.1, D76.

Advancing the treatment of juvenile idiopathic arthritis.

Treatment for juvenile idiopathic arthritis has undergone substantial changes in recent decades. These changes are partly due to the availability of new treatments, mainly biological agents, as well as developments in treatment strategies, including a focus on concepts such as treat-to-target. In addition, the creation of large paediatric research networks has improved patient access to, and design of, clinical trials for rare paediatric diseases.

Macrophage Activation Syndrome in Children: Diagnosis and Management.

Macrophage activation syndrome is a severe yet under-recognized complication encountered in pediatric rheumatology. It manifests as secondary hemophagocytic lymphohistiocytosis leading to a hyper-inflammatory state resulting from an underlying cytokine storm. If unchecked, it may lead to multiorgan failure and mortality.

Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?-observations from the UK JSLE Cohort Study.

Objectives: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE.

Methods: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria.

Update on noninfectious uveitis in children and its treatment.

Purpose Of Review: To give an overview of recently published articles covering risk factors, novel biomarkers and treatment for noninfectious uveitis in children.

Recent Findings: In the last few years, several genetic markers, serum biomarkers, aqueous humor markers, tear biomarkers and clinical factors have been identified, which are associated with childhood noninfectious uveitis. We describe the most important reports in this field that may help to tailor the screening and monitoring of this population in the future and might become the target of novel therapies.

Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome.

Background And Objectives: Intensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study of Nephrotic Syndrome cohort aimed to improve disease stratification by determining, in comprehensively genetically screened patients with steroid-resistant nephrotic syndrome, if there is an association between response to initial intensified immunosuppression and disease progression and/or post-transplant recurrence.

Design, Setting, Participants, & Measurements: Pediatric patients with steroid-resistant nephrotic syndrome were recruited the UK National Registry of Rare Kidney Diseases.

Juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The uveitis is potentially sight-threatening and so carries a considerable risk of morbidity. The commonest form of uveitis seen in JIA is chronic anterior uveitis which is almost always asymptomatic in the initial stages.

Juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The uveitis is potentially sight-threatening and thus carries a considerable risk of morbidity with associated reduction in quality of life. The commonest form of uveitis seen in association with JIA is chronic anterior uveitis, which is almost always asymptomatic in the initial stages.

Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations.

Background: There are many single-gene causes of steroid-resistant nephrotic syndrome (SRNS) and the list continues to grow rapidly. Prompt comprehensive diagnostic testing is key to realising the clinical benefits of a genetic diagnosis. This report describes a bespoke-designed, targeted next-generation sequencing (NGS) diagnostic gene panel assay to detect variants in 37 genes including the ability to identify copy number variants (CNVs).

Cross sectional, qualitative thematic analysis of patient perspectives of disease impact in juvenile idiopathic arthritis-associated uveitis.

Background: Chronic health conditions in children can have a significant impact on their quality of life. The aim of this study was to explore the subjective experience of children and young people being treated for chronic, non-infectious uveitis associated with a systemic disease such as juvenile idiopathic arthritis.

Methods: A semi-structured interview was conducted with 10 children and young people aged between 6 and 18 years of age and their parents.

Chronic recurrent multifocal osteomyelitis in children and adults: current understanding and areas for development.

Since the first descriptions of chronic recurrent multifocal osteomyelitis in the 1970s, there have been numerous case reports in the literature; both unusual case reports and case series from all over the world. Our understanding of the pathogenesis has significantly changed, with it now being regarded as an autoinflammatory condition. Treatment options have also expanded, but little progress has been made in developing the evidence for treatments.

Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis.

Diagnosing haemophagocytic syndrome.

Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory disorder characterised by uncontrolled activation of the immune system. It can result from mutations in multiple genes involved in cytotoxicity or occur secondary to a range of infections, malignancies or autoimmune rheumatic diseases. In the latter case, it is also known as macrophage activation syndrome (MAS).

Juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells.

Macrophage Activation Syndrome.

Macrophage activation syndrome (MAS) is a potentially life-threatening complication of rheumatic diseases such as systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus. It is often considered a type of secondary hemophagocytic lymphohistiocytosis (HLH) and results from over-activation of T lymphocytes and macrophages leading to a "cytokine storm". Characteristic features are persistent fever, lymphadenopathy, hepatosplenomegaly, cytopenias (anemia, leucopenia, thrombocytopenia), raised C-reactive protein, falling erythrocyte sedimentation rate, hypofibrinogenemia, transaminitis, hypertriglyceridemia and extreme hyperferritinemia often associated with multi-organ impairment.