Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in the paediatric population. JIA comprises a heterogeneous group of disorders with different onset patterns and clinical presentations with the only element in common being chronic joint inflammation. This review sought to evaluate the most relevant and up-to-date evidence on current knowledge regarding the pathogenesis of JIA subtypes to provide a better understanding of these disorders. Despite significant improvements over the past decade, the aetiology and molecular mechanisms of JIA remain unclear. It has been suggested that the immunopathogenesis is characterised by complex interactions between genetic background and environmental factors that may differ between JIA subtypes. Human leukocyte antigen (HLA) haplotypes and non-HLA genes play a crucial role in the abnormal activation of both innate and adaptive immune cells that cooperate in causing the inflammatory process. This results in the involvement of proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin (IL)-1, IL-6, IL-10, IL-17, IL-21, IL-23, and others. These mediators, interacting with the surrounding tissue, cause cartilage stress and bone damage, including irreversible erosions. The purpose of this review is to provide a comprehensive overview of the genetic background and molecular mechanisms of JIA.

Pain is the most common complaint reported by children who access the emergency departments, but despite its frequency and the availability of many international guidelines, it often remains underreported and undertreated. Recently, the American Academy of Pediatrics and the American Pain Society have reiterated the importance of a multidisciplinary approach in order to eliminate pain in children. In all pediatric settings, an adequate assessment is the initial stage in a proper clinical approach to pain, especially in the emergency departments; therefore, an increasing number of age-related tools have been validated. A wide range of analgesic agents are currently available for pain management, and they should be tailored according to the patient’s age, the drug’s pharmacokinetics and the intensity of pain. In order to facilitate the choice of the appropriate drug, a treatment algorithm based on a ladder approach can be used. Moreover, non-pharmacological techniques should be considered to alleviate anxiety and distress in pediatric age. This review aims to offer a simple but intuitive description of the best strategies for pain relief in children, starting with the prompt recognition and quantification of pain through adequate assessment scales, and following with the identification of the most appropriate therapeutic choice among the ones available for pediatric age.

pathogenesis. Clinical heterogeneity and confounding factors also impair the search for alternative mechanisms. Therefore, we studied the CSF of 13 patients with neurological symptoms during the acute phase of their hospitalization, looking for clues suggesting a specific dysimmune phenomenon. MethodsCSF underwent conventional analysis and RT-PCR for SARS-CoV-2; a in-house HEK293 cell-based assay was also arranged to identify anti-spike antibodies. Albumin ratio, IgG index and oligoclonal bands were also assessed, along with a screening for autoimmune antibodies. First, commercial immunofluorescence and lineblot were used to detect common neuronal surface and intracellular antibodies, respectively; secondly, immunohistochemistry was performed on rat brain sections; lastly, CSF was incubated with fixed murine neuron and astrocyte cultures to confirm a potential auto-reactivity. ResultsCSF analysis disclosed a slightly increased protein level with a non-significant cell count (0-10 cells/uL). Neither SARS-CoV-2 nor common neuronal antibodies were detectable in the CSF, but we recognized anti-spike IgGs. 69% of the samples also showed neuropil staining, some of which had a common staining pattern involving the hippocampal dentate gyrus. Rodent primary cultures confirmed the presence of autoreactive antibodies against epitopes that are expressed in cortical neurons and/or astrocytes in most samples. ConclusionsA strong immunoreactivity against spike protein was found in the CSF of those patients, even without a significant blood brain barrier permeability. The detection of auto reactivity with two different techniques could thus represent a dysimmune response to COVID-19 infection, perhaps suggesting molecular mimicry.

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)-α, and proteins belonging to type I-interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low-molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro-inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non-amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type-I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement.

Deep neck space infections (DNSI) are defined as infections in the potential spaces and fascial planes of the neck. We show the clinical case of a retro and para-pharyngeal abscess in a healthy 5-year-old child complicated by compression and dislocation of the larynx with marked airway caliber reduction and potentially fatal extension up to the mediastinal aditus. DNSI can occur at any age and, due to its rapid progression, requires immediate treatment in children. In healthy children, concurrent abscesses in separate neck spaces are rare. DNSI recurrence should alert the physician to the possibility of a congenital problem, and if imaging fails, laryngoscopy may be the best diagnostic technique.