Still Disease

This study aims to assess and characterize the treatment patterns, and long-term clinical outcomes and demographic characteristics of patients diagnosed with Familial Mediterranean fever (FMF) and Still's disease (including systemic juvenile idiopathic arthritis \[SJIA\] and adult-onset Still's disease \[AOSD\]) that received canakinumab for at least 6 months.

Inflammatory Cardiovascular Diseases and Autoimmune Rheumatic Diseases (ICARDs) encompass cardiovascular involvement in connective tissue diseases, vasculitis, and primary inflammatory cardiac processes affecting all layers of the heart. ICARDs are associated with increased cardiovascular morbidity and mortality, independently of traditional risk factors, via multiple pathophysiological mechanisms. Diagnosis and prognosis are challenged by the heterogeneity of clinical presentations. Multimodality cardiovascular imaging - including cardiovascular magnetic resonance (CMR), transthoracic echocardiography, and positron emission tomography (PET) - plays a central role in detecting and characterizing inflammatory involvement, and may offer prognostic insights. Given the limited data on the diagnostic and prognostic utility of these imaging modalities in ICARDs, the EACVI-INFLAME study aims to assess the prevalence of confirmed cardiovascular involvement in patients with suspected or established ICARDs undergoing CMR and/or cardiac PET in a multicentric international cohort.

The primary objective of the study is to evaluate the efficacy and safety of goflikicept (GFC) and olokizumab (OKZ) in patients with Still's disease

Adult Onset Still Disease (AOSD) and Systemic onset Juvenile Idiopathic Arthritis (SoJIA) are two rare multifactorial diseases associated with systemic inflammation. These two forms AOSD and SoJIA are considered to be two facets of the same syndrome, combining four cardinal symptoms \[hectic fever\> 39 °, arthralgia or arthritis, skin rash, a leukocyte formula with more than 80% of neutrophils\]; lymphadenopathy and splenomegaly may also be found. There is an important biological inflammatory syndrome with elevation of the reactive C protein, of serum ferritin with a dramatic drop in the glycosylated fraction. The incidence of the disease is low, around 0.1/100,000 for adults and 0.6/100,000 for children. Its prevalence is approximately 1 to 3/100,000 and 3/100,000 for children, so there are approximately 500 to 1,500 adults and 450 children affected in France. It is subdivided into pediatric and adult forms according to the age of onset before or after 16 years. The prognosis of the disease is functional and vital. Macrophage activation syndrome (SAM) is frequently associated with either the onset of the disease or the initiation of treatment or concomitantly with viral reactivation. The course over time has mainly been studied in children and is variable: regression, course by flare-ups with term regression and chronic joint development. In adults we can also observe these 3 evolutionary modes. However, differences seem to exist between AOSD and SoJIA. The various clinical questions posed by this disease are as follows: * Why does it differentially affect two age groups of the population? * Why is the clinical expression heterogeneous with pure systemic or articular forms, the frequency of SAM, and rare organ damage? * Why is the evolution over time different with resolving monocyclic forms or polycyclic forms and sometimes chronic evolutions? These differences could be explained by distinct underlying pathogenic mechanisms. But at present, the pathophysiology of this entity remains unknown, although several hypotheses can be formulated involving several pathophysiological pathways. The pathogenesis of Still's disease has not yet been elucidated but there is a significant inflammatory reaction without the production of autoantibodies, which makes this disease a form of autoinflammatory syndrome with abnormalities of the innate immunity (activation of macrophages, strong elevations of pro-inflammatory cytokines: interleukins 1 and 18, possible abnormalities of inflammasomes and NK cells). The treatment is based on anti-inflammatory drugs, corticosteroids with the usefulness of methotrexate and anti-TNF in the event of significant joint damage. Interleukin 1 and 6 inhibitors have been shown to be effective in this disease. In adults and children, there are forms that are refractory to treatment, with a risk of AA amyloidosis for these patients. The expected outcomes of this work are to improve knowledge of Still disease and patient management on the following aspects: * Comparison of pediatric and adult forms (which has never been done on a large number of patients), * Better understanding of the pathogenic mechanisms of the disease, * The identification of early diagnostic/prognostic markers, * The possibility of promoting the evaluation of new therapies to come thanks to the constitution of an active file of patients with a standardized follow-up. The ACOSTILL study group is thus a unique collaboration of adult clinicians (rheumatologists and internists) and pediatricians, who have decided to unite their efforts to increase knowledge about the pathogenesis of Still disease in order to better understand the disease and improve care pathways. Many of them participated in the development of the national diagnostic and care protocol published in 2018.

Autoinflammatory diseases (AIDs) are a group of rare disorders caused by dysregulation of the innate immune system, characterized by recurrent fever, systemic inflammation, and involvement of specific organs. Diagnosis relies on a combination of clinical features, laboratory tests, genetic findings, and response to treatment. Still's disease is a representative type of AID, marked by high spiking fevers, polyarthritis, evanescent rash, and markedly elevated inflammatory markers. Among its complications, macrophage activation syndrome (MAS) is the most life-threatening, affecting approximately 10-15% of patients. MAS involves uncontrolled immune activation and systemic inflammation, and if left untreated, may result in a mortality rate exceeding 50%. This study aims to develop a standardized clinical dataset and diagnostic-treatment framework for AIDs based on their disease characteristics. After establishing a data collection template, eligible patients aged 18-75 years with AIDs will be enrolled. Clinical data will be collected to build a prospective follow-up cohort, focusing particularly on adult-onset Still's disease (AOSD), to explore the clinical features and pathogenesis of AIDs.

Autoinflammatory diseases (AID) are clinical entities characterized by recurrent inflammatory attacks in absence of infection, neoplasm or deregulation of the adaptive immune system. Among them, hereditary periodic syndromes, also known as monogenic AID, represent the prototype of this disease group, caused by mutations in genes involved in the regulation of innate immunity, inflammation and cell death. Based on recent experimental acquisitions in the field of monogenic AID, several immunologic disorders have been reclassified as polygenic/multifactorial AID, sharing pathogenetic and clinical features with hereditary periodic fevers. This has paved the way to new treatment targets for patients suffering from rare diseases of unknown origin, including Behçet's disease, Still disease, Schnitzler's disease, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) syndrome, chronic recurrent multifocal osteomyelitis (CRMO), non-infectious uveitis and scleritis. Gathering information on such rare conditions is made difficult by the small number of patients, along with the difficulty of obtaining an accurate diagnosis in non-specialized clinical settings. In this context, the AIDA project promotes international collaboration among clinical centres to develop a permanent registry aimed at collecting demographic, genetic, clinical and therapeutic data of patients affected by monogenic and polygenic AID, in order to expand the current knowledge of these rare conditions.