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.

The AIDA registry service is based on REDCap (Research Electronic Data Capture, project-redcap.org), a secure web application for building and managing online surveys and databases, designed to support data capture for research studies. The platform is directly accessible through the AIDA website, after inserting a personal username and password. Currently, 11 registries are available, each one dedicated to the collection of data about:

• monogenic AID
• PFAPA syndrome
• undifferentiated systemic AID (USAID)
• Behçet's disease
• Schnitzler's disease
• VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome
• Still disease
• noninfectious uveitis
• noninfectious scleritis
• spondyloarthritis
• Castleman disease

The registry will pursue the following aims within the first 36 months from the start of the enrollment:

1. to identify any association between clinical manifestations and gender, disease duration, body mass index and tabagism;
2. to detect differences in the clinical phenotype between pediatric-onset and adult-onset patients;
3. to identify the impact of different treatment approaches on clinical and laboratory disease manifestations.

Additional aims of the AIDA project, to be reached over the next 10 years, are the following:

1. to overcome fragmentation in the clinical experience on these rare conditions by sharing the knowledge at the international level;
2. to improve knowledge about the clinical presentation, genotype-phenotype correlations, response to treatment, long-term complications and social impact when monogenic and polygenic AID manifest during either childhood or adulthood;
3. to identify the long-term clinical course of patients diagnosed with monogenic or polygenic AID;
4. to promote awareness among physicians and enhance early recognition of these diseases;
5. to describe the impact of AID on quality of life;
6. to identify any impact of monogenic and polygenic AID on fertility;
7. to study the course of AID during pregnancy;
8. to assess the socioeconomic impact of AID;
9. to promote future multicentric studies.

Data collection is both retrospective and prospective. It includes demographic, clinical, diagnostic, genetic, clinimetric, laboratory, radiologic, therapeutic and socio-economic data. Instruments are designed to be filled out during routine clinical visits, usually scheduled every 3-6 months. Separation of personally identifiable information and medical data by using only pseudonyms for storing medical data ensures compliance with data protection regulations. The description of symptoms, diseases, procedures and injuries is based on the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 coding system. Data management is both central and decentral. Data are extracted and statistically analyzed on a regular basis according to individual study protocols. A policy for authorship and dissemination of research findings is in place among the AIDA partners contributing to the registry.

The AIDA registry will support data collection for the conduction of clinical trials, observational studies, comparative effectiveness research, and other research on patients with monogenic and polygenic AID.

Several healthcare providers contributing to the AIDA Network are members of the European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA).

Inclusion Criteria:

• to be diagnosed with a monogenic AID according to the clinical phenotype and the detection of a confirmative genotype;
• to be diagnosed with clinical familial Mediterranean fever or Behçet's disease or Still disease or PFAPA syndrome or Schnitzler's disease or CRMO according to the corresponding clinical diagnostic and/or classification criteria;
• to be diagnosed with undifferentiated systemic AID;
• to be diagnosed with non-infectious uveitis according to the standardization for uveitis nomenclature (SUN) criteria;
• to be diagnosed with anterior or posterior non-infectious scleritis;
• to be diagnosed with spondyloarthritis according to ASAS and/or New York criteria;
• to be diagnosed with Castleman disease;

Exclusion Criteria:

- informed consent/assent not provided by the patient and/or his/her legal representative.

Patients consecutively diagnosed and treated at the hospitals/ research centres affiliated to the AIDA Network (https://aidanetwork.org/en/)