Kawasaki Disease

Kawasaki disease (KD) is an acute-onset systemic vasculitis of medium-sized vessels that mostly affects infants and toddlers. Globally, it is the most common form of childhood primary vasculitis. Delayed diagnosis and treatment results in coronary artery aneurysms in up to 25% of all affected individuals. Thus, KD is the most common acquired heart disease in developed countries. Here, the current understanding of clinical presentations, pathophysiological concepts, disease-associated complications, and available pharmaceutical treatment is provided and discussed in the context of available literature

Biosimilars in pediatric rheumatology and their introduction into routine care

Biosimilars are biologic medications that are slightly altered versions of already approved biologic disease modifying anti-rheumatic drugs (bDMARDs). They can be manufactured after the original product's patent protection expires. The advent of biosimilar use in pediatric rheumatology started with the biosimilar to infliximab in 2013. Since then, more biosimilars have been made available including etanercept, rituximab and adalimumab. This manuscript briefly reviews the history of biosimilar introduction to treatment and suggests strategies for the adoption of biosimilar drugs in services specialized in Pediatric Rheumatology, including potential barriers and solutions to their implementation into practice. The review covers general aspects relevant to all biosimilar drugs and specific examples covering individual drugs based on the experience of a large tertiary pediatric rheumatology service in the Northwest of England

Update: Cytokine Dysregulation in Chronic Nonbacterial Osteomyelitis (CNO)

Chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is a non-bacterial osteitis of yet unknown origin. Secondary to the absence of both high-titer autoantibodies and autoreactive T lymphocytes, and the association with other autoimmune diseases, it was recently reclassified as an autoinflammatory disorder of the musculoskeletal system. Since its etiology is largely unknown, the diagnosis is based on clinical criteria, and treatment is empiric and not always successful. In this paper, we summarize recent advances in the understanding of possible etiopathogenetic mechanisms in CNO

Innately adaptive or truly autoimmune.

Systemic juvenile idiopathic arthritis (sJIA) is a form of arthritis in childhood that is initially dominated by innate driven systemic inflammation and is thus considered a polygenic autoinflammatory disease. However, sJIA can progress towards an adaptive immunity driven afebrile arthritis. Based on this observation of bi-phasic disease progression, a "window-of-opportunity" for optimal, individualized and target-directed treatment has been proposed. This hypothesis requires testing and in this review we summarize current evidence regarding molecular factors that may contribute to the progression from an initially predominantly autoinflammatory disease phenotype to autoimmune arthritis. We consider the involvement of innately adaptive γδT and NKT cells that express γδ or αβ T cell receptors but can be neither classified as purely innate or adaptive cells, versus classical B and T lymphocytes in this continuum. Finally, we discuss our understanding of how and why some primarily autoinflammatory conditions can progress towards autoimmune-mediated disorders over the disease course while others do not and how this knowledge may be used to offer individualized treatment

Demographic, clinical and laboratory differences between paediatric acute COVID-19 and PIMS-TS—results from a single centre study in the UK

BackgroundPaediatric symptomatic SARS-CoV-2 infections associate with two presentations, acute COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Phenotypic comparisons, and reports on predictive markers for disease courses are sparse and preliminary.MethodsA chart review of COVID-19 and PIMS-TS patients (≤19 years) admitted to Alder Hey Children's NHS Foundation Trust, a tertiary centre in the North-West of England, was performed (02/2020–09/2022).ResultsA total of 161 symptomatic COVID-19 and 50 PIMS-TS patients were included. Peaks in admissions of patients with PIMS-TS occurred approximately 4 weeks after those for acute COVID-19. The incidence of in-patients with PIMS-TS reduced over time, and there were no admissions after February 2022. When compared to acute COVID-19, PIMS-TS patients were older (median: 10.3 years vs. 2.03 years; p < 0.001). There were no differences in gender distribution, but minority ethnicities were over-represented among PIMS-TS patients. Regional ethnic distribution was reflected among acute COVID-19 patients (66% vs. 84.5% White Caucasian, p = 0.01). Pre-existing comorbidities were more common among acute COVID-19 patients (54.7% vs. 8%, p < 0.001). PIMS-TS patients more commonly presented with abdominal symptoms (92% vs. 50.3%), neurological symptoms (28% vs. 10.6%) and skin rashes (72% vs. 16.8%), (p ≤ 0.01) when compared with acute COVID-19, where respiratory symptoms were more common (51.6% vs. 32%, p = 0.016). PIMS-TS more frequently required intensive care admission (64% vs. 16.8%), and inotropic support (64% vs. 9.3%) (all p < 0.05). More deaths occurred among acute COVID-19 patients [0 vs. 7 (4.4%)], with 5/7 (71%) in the context of pre-existing comorbidities. When compared to acute COVID-19, PIMS-TS patients exhibited more lymphopenia and thrombocytopenia, a more pronounced acute phase reaction, and more hyponatraemia (p < 0.05). Partial least square discriminant analysis of routine laboratory parameters allowed (incomplete) separation of patients at diagnosis, and variable importance projection (VIP) scoring revealed elevated CRP and low platelets as the most discriminatory parameters.ConclusionAdmissions for PIMS-TS reduced with increasing seroconversion rates in the region. Young age and pre-existing comorbidities associate with hospital admission for acute COVID-19. While PIMS-TS may present more acutely with increased need for intensive care, acute COVID-19 had an increased risk of mortality in this cohort

New Insights into Adult and Paediatric Chronic Non-bacterial Osteomyelitis CNO

Purpose of Review To describe in detail the clinical synopsis and pathophysiology of chronic non-bacterial osteomyelitis and SAPHO syndrome. Recent Findings Chronic non-bacterial osteomyelitis (CNO) has been identified as a disease entity for almost 50 years. This inflammatory bone disorder is characterized by osteolytic as well as hyperostotic/osteosclerotic lesions. It is chronic in nature, but it can present with episodic flairs and phases of remission, which have led to the denomination “chronic recurrent osteomyelitis”, with its severe multifocal form “chronic recurrent multifocal osteomyelitis” (CRMO). For almost three decades, an infectious aetiology had been considered, since especially Propionibacterium acnes had been isolated from bone lesions of individual patients. However, this concept has been challenged since long-term antibiotic therapy did not alter the course of disease and modern microbiological techniques (including PCR) failed to confirm bone infection as an underlying cause. Over recent years, a profound dysregulation of cytokine expression profiles has been demonstrated in innate immune cells of CNO patients. A hallmark of monocytes from CNO patients is the failure to produce immune regulatory cytokines interleukin-10 (IL-10) and IL-19, which have been linked with genetic and epigenetic alterations. Subsequently, a significant upregulation of pro-inflammatory, NLRP3 inflammasome-dependent cytokines (IL-1β and TNF-α), has been demonstrated. Summary The current knowledge on CNO, the underlying molecular pathophysiology, and modern imaging strategies are summarized; differential diagnoses, treatment options, outcome measures, as well as quality of life studies are discussed