NETosis in Rheumatic Diseases.

PURPOSE OF REVIEW: Neutrophils are the most numerous and the first responder cells of the innate immune system. Evidence suggests that neutrophils may play an essential role in the pathogenesis of multiple systemic diseases. A novel mechanism of neutrophil extracellular traps (NETs) leading to breaking of self-tolerance and generation of autoimmune responses in predisposed individuals has been described in various autoimmune conditions. The purpose of the review is to identify these important mechanisms of NETs leading to autoimmunity in various rheumatic diseases. RECENT FINDINGS: NETs contain histone and chromatin, which contain important autoantigens. Many autoimmune conditions are associated with increased NET-generating capacity, unique low-density granulocyte population, and impaired NET degradation leading to persistent inflammation and tissue damage. NETs can also activate other immune cells, and their components may amplify the inflammatory response by activation of complement pathways and inflammasomes. NETs can also contribute to autoantibody formation in disorders such as rheumatoid arthritis, ANCA-associated vasculitis, and systemic lupus erythematosus by providing a constant source of autoantigens. NETs can also serve as biomarkers providing insights into disease diagnosis and therapeutics. NETs seem to play a primary role in inflammatory disease pathogenesis. Identification of different NET pathogenic pathways in various rheumatic conditions could provide new insights into disease pathogenesis and therapeutic targets could be developed towards the future treatment of inflammatory autoimmune diseases.

Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome: differential diagnosis and review of the literature.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autosomal-dominant autoinflammatory disease of incomplete penetrance and variable expression. PAPA syndrome is the result of a mutation in the proline serine threonine phosphatase-interacting protein 1 (PSTPIP1/CD2BP1) gene located on chromosome 15, which results in an abnormal overproduction of the pro-inflammatory cytokine interleukin-1ß (IL-1). This syndrome clinically manifests as early onset of recurrent episodes of acute aseptic inflammation of the joints, generally occurring in the first two decades of life, followed by manifestation of characteristic skin lesions in the third decade, after an obvious decline in the joint symptoms. Although uncommon, the potential clinical implications of PAPA syndrome warrant an appropriate diagnosis in a timely fashion.

Choosing Wisely: The Canadian Rheumatology Association Pediatric Committee's List of Items Physicians and Patients Should Question.

OBJECTIVE: To develop a list of tests or treatments frequently used in pediatric rheumatology practice that may be unnecessary based on existing evidence. METHODS: A Choosing Wisely (CW) working group composed of 16 pediatric rheumatologists, 1 allied health professional, 1 parent, and 1 patient used the Delphi method to generate, rank, and refine a list of tests and treatments that may be unnecessary or harmful. The items with the highest content agreement and perceived impact were presented in a survey to all Canadian Rheumatology Association (CRA) physicians who practice pediatric rheumatology. Respondents were asked to rate their agreement and impact, and to rank the items. Five items with the highest composite scores and 2 additional items selected by the CW working group were put forward for literature review. RESULTS: The initial Delphi procedure generated 80 items. After 3 rounds, the list was narrowed to 13 items. The survey was completed by 41/81 (51%) CRA pediatric members across Canada. Respondent characteristics were similar to those of the CRA pediatric membership for self-reported gender, geographical location, and career stage. The highest composite score items were antinuclear antibody testing, drug toxicity monitoring, HLA-B27 testing, rheumatoid factor/anticyclic citrullinated peptide testing, and Lyme serology testing. Two additional items (numerous or repeated intraarticular corticosteroid injections, and autoinflammatory diseases genetic testing) were also selected. Literature review was performed for these 7 highest priority items. CONCLUSION: We have identified areas for quality improvement in the evaluation and treatment of rheumatic diseases in Canadian children.

Primary Vasculitis in Childhood: GPA and MPA in Childhood.

Childhood onset anti-neutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare group of primary systemic vasculitides affecting medium and small blood vessels. AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal limited ANCA vasculitis. These disorders are associated with severe clinical manifestations, frequent relapses and a high cumulative morbidity, and often present with multisystem involvement. Renal involvement is common in the pediatric age group, characterized by pauci-immune necrotizing and crescentic glomerulonephritis which frequently progresses to chronic kidney disease in adulthood. ANCAs against proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) remain the hallmark of AAV and are integral to the disease pathogenesis. Newer understanding of neutrophil extracellular traps and complement activation have provided better insights into disease pathogenesis. A pediatric vasculitis working group has developed and validated childhood vasculitis classification criteria and disease activity and damage scores. No specific pediatric treatment recommendations exist due to rare nature of the illness in pediatric population. Smaller case series have been published on the efficacy of adult treatment regimens in pediatric patients. The prognosis often remains guarded with frequent relapses and a high cumulative morbidity. The aim of this article is to provide a comprehensive review on pediatric AAV with a focus on recent observations regarding epidemiology, disease pathogenesis, treatment, and prognosis.