The everchanging framework of autoinflammation

Abstract

The innate immunity works as a defence bullwark that safeguards healthy tissues with the power of detecting infectious agents in the human body: errors in the context of innate immunity identify autoinflammatory disorders (AIDs), which arise as bouts of aberrant inflammation with little or no involvement of T and B cells and neither recognized infections, nor associated autoimmune phenomena. Hereditary AIDs tend to have a pediatric-onset heralded by stereotyped inflammatory symptoms and fever, while AIDs without an ascertained cause, such as systemic juvenile idiopathic arthritis, derive from the interaction of genetic factors with environmental noxae and are unevenly defined. A dysregulated inflammasome activation promotes the best-known family of AIDs, as well as several degenerative and metabolic disorders, but also nuclear factor κB- and interferon-mediated conditions have been framed as AIDs: the zenith of inflammatory flares marks different phenotypes, but diagnosis may go unnoticed until adulthood due to downplayed symptoms and complex kaleidoscopic presentations. This review summarizes the main AIDs encountered in childhood with special emphasis on the clinical stigmata that may help establish a correct framework and blueprints to empower young scientists in the recognition of AIDs. The description focuses inflammasomopathies as paradigms of interleukinopathies, nuclear factor-κB -related disorders and interferonopathies. The challenges in the management of AIDs during childhood have been recently boosted by numerous therapeutic options derived from genomically-based approaches, which have led to identify targeted biologic agents as rationalized treatments and achieve more tangible perspectives of disease control.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome

“…Indeed, current evidence on rare diseases is almost based on small individual studies conducted by one or only a few centers (29). On the contrary, a worldwide basis of data collection will ultimately allow the resolution of old riddles about PFAPA syndrome, such as its genetic origin or influence -at least in some cases -which is currently controversial and not fully understood (1,30,31); the boundary line between some PFAPA subgroups and Behçet's disease, which may be very fine in some cases (16,32); to describe uncommon symptoms and eventually individuate new subgroups of patients, who respond differently to various treatments (33); to better understand the different behaviors of the disease according to the age at disease onset. This registry may also join the research ambitions toward the achievement of a personalized medicine aimed at choosing the right treatment according to baseline features or risks to develop severe manifestations and potential longterm complications.…”

Assessment of Congenital Neutropenia in Children: Common Clinical Sceneries and Clues for Management

“…64 In contrast with cyclic neutropenia, these children have high white blood cell counts with preponderance of neutrophils and high levels of inflammatory markers during febrile episodes, while the neutrophil count turns to normal in the interfebrile periods. 65 Procalcitonin, a significant marker of bacterial infections, does not increase during PFAPA attacks, while serum immunoglobulins are usually normal during attacks. 66 The discrimination between PFAPA syndrome and cyclic neutropenia may be particularly challenging, as it requires a painstaking collection of clinical and laboratory data, and this challenge also involves the area of internal medicine, as PFAPA symptoms have been reported even in adulthood.…”

An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children

“…Despite over 50 years of clinical observations and in-depth research, the exact etiology of KD remains unknown, although the main pathogenetic disease mechanisms recall a dramatic inflammatory response in genetically predisposed children following a ‘potential’ infectious trigger [ 9 ]. Indeed, KD mainly affects children with a likely genetic susceptibility and is nowadays conceived as a systemic multifactorial autoinflammatory disorder [ 10 , 11 ] due to its similarity with hereditary autoinflammatory diseases, which arise from specific dysregulation of innate immunity with no specific age or gender distribution [ 12 , 13 ]. The objective of our research was to review the medical literature about case reports of KD in relation to the diagnosis of atypical disease presentations and the potential identification of predictors of non-response to intravenous immunoglobulin (IVIG).…”