A20 haploinsufficiency (HA20) is an autoinflammatory disease caused by defective inactivation of NF-κB pathway. We conducted a systematic literature review of articles reporting patients with TNFAIP3 mutations from 2016 to August 2023 following PRISMA guidelines. Data of 177 patients from 65 articles were retrieved (108 women). The principal features were: mucosal ulcers (n=129), fever (n=93) followed by gastrointestinal (n=81), skin features (n=76), autoimmunity (n=61) including thyroiditis (n=25) and Lupus (n=16), and joint involvements (n=54). Five patients had died at the time of publication. In 54/63 patients, C9 reactive protein was significantly elevated during flares, with a median of 51mg/L. Most commonly used treatment included corticosteroids and non-steroidal anti-inflammatory drugs (n=32), TNF-blockers (n=29), colchicine (n=28) and methotrexate (n=14). TNFAIP3 variants impacted the OTU domain in 92 cases and a Zinc finger domain in 68 cases. Geographic origin, gender and variant type significantly impacted phenotype. A better understanding of the wide HA20 phenotype could facilitate the diagnosis process. Much remains to be elucidated about 15 pathogenesis and treatment to improve outcome in HA20 patients.