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Monogenic autoinflammatory diseases (mAIDs) are inherited errors of innate immunity characterized by systemic inflammation recurring with variable frequency and involving the skin, serosal membranes, synovial membranes, joints, the gastrointestinal tube, and/or the central nervous system, with reactive amyloidosis as a potential severe long-term consequence. Although individually uncommon, all mAIDs set up an emerging chapter of internal medicine: recent findings have modified our knowledge regarding mAID pathophysiology and clarified that protean inflammatory symptoms can be variably associated with periodic fevers, depicting multiple specific conditions which usually start in childhood, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndrome, and mevalonate kinase deficiency. There are no evidence-based studies to establish which potential genotype analysis is the most appropriate in adult patients with clinical phenotypes suggestive of mAIDs. This review discusses genetic and clinical hints for an ideal diagnostic approach to mAIDs in adult patients, as their early identification is essential to prompt effective treatment and improve quality of life, and also highlights the most recent developments in the diagnostic work-up for the most frequent hereditary periodic febrile syndromes worldwide.

ObjectiveAim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions.ResultsStarting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access.ConclusionsThis international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from “real-life” data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at https://clinicaltrials.gov/.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described pathological entity. It is an acquired monogenic autoinflammatory disease caused by somatic mutations of the UBA1 gene in blood cells precursors; the gene encodes one of the two E1 enzyme isoforms that initiates ubiquitylation in cell’s cytoplasm. VEXAS syndrome leads to systemic inflammation, with all organs and tissues potentially involved. The clinical picture may be extremely heterogenous, mimicking different other systemic rheumatologic entities coexisting with haematological disorders, especially myelodysplastic syndrome. This new disease represents a very intriguing clinical condition in several respects: it accounts for the paradigm of adult-onset monogenic autoinflammatory diseases determined by a genetic mosaicism resulting in the development of a challenging multiorgan inflammatory condition. Moreover, VEXAS syndrome is perhaps not an exceptionally rare condition and represents an example of a systemic genetic autoinflammatory disease drawing its origin in bone marrow disorders. VEXAS syndrome should be strongly considered in each adult patient with an unexplained systemic inflammatory condition, especially when recurrent fevers, neutrophilic dermatosis, relapsing polychondritis, ocular inflammation and other systemic inflammatory symptoms accompanying myelodysplastic syndrome or other haematological disorders. The syndrome deserves a multidisciplinary approach to reach the diagnosis and ensure the best management of a potentially very challenging condition. To quickly describe the clinical course, long-term outcomes, and the optimal management of this new syndrome it is essential to join forces internationally. To this end, the international AutoInflammatory Disease Alliance (AIDA) registry dedicated to VEXAS syndrome has been developed and is already active.