Palindromic Rheumatism: Autoimmunity, Inflammation or Both? Evidence for Four Subtypes of Palindromic-Like Arthritis Based in Either MEFV or RF/ACPA Status

Background: MEFV mutations were documented in patients with palindromic rheumatism (PR) who do not meet Familial Mediterranean Fever (FMF) criteria, and RF and ACPA positive rheumatoid arthritis (RA) may start with PR. We retrospectively analyzed the clinical phenotype and disease evolution of patients with palindromic-like (PR-L) arthritis according to ACPA/RF and MEFV mutation status. Methods: MEFV genotyping was undertaken in 76 patients with PR-L arthritis as determined by short attacks ( < 7 days) and relapsing course. Characteristics of arthritis episodes, RF and ACPA positivity, and colchicine response were retrospectivelly collected. Patients were stratified according the presence of MEFV mutations and/or ACPA/RF status. Findings: 26.3% (20/76) of patients had MEFV mutations and 23 (30%) were ACPA and/or RF positive. After stratification, we can distinguish four groups of PR-L arthritis patients. Group I (MEFV +ve) with younger age of onset, short duration attacks ( 3 days, and 15 patients developed criteria of immune-mediated inflammatory (IMID), autoinflammatory or infectious disease. Group IV (MEFV +ve associated to pre-existing IMID) had very short-attacks (<3 days) superimposed to a definite IMID, included RA, with good response to colchicine. Interpretation: Patients with palindromic-like arthritis can be classified in four groups according to the presence or not of MEFV mutations and ACPA/RF antibodies with different clinical evolution and therapeutic response.  Funding Statement: Instituto de Salud Carlos III, Spain. Grant PI17/00993 to Juan D Canete. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All the patients signed an informed consent approved by the Ethical Committee of the Hospital Clinic, Barcelona.