Palindromic rheumatism: Evidence of four subtypes of palindromic-like arthritis based in either MEFV or RF/ACPA status

Introduction: MEFV mutations have been documented in patients with palindromic rheumatism (PR) who do not meet FMF criteria, and RF and ACPA positive RA may start with PR.

Objective: To analyze the clinical phenotype and disease evolution of patients with intermittent, palindromic-like (PL) arthritis seen in our Arthritis Unit according to the RF, ACPA and MEFV mutation status.

Methods: MEFV genotyping was done in 76 patients with PL arthritis as defined by predominantly short attacks (<7 days) and a relapsing course. Characteristics of arthritic episodes, RF and ACPA positivity, and the colchicine response were retrospectively collected. Patients were stratified and evaluated according to MEFV mutations and/or positive autoantibodies (ACPA and/or RF).

Results: 26.3% (20/76) of patients had a MEFV mutation and 23 (30%) were ACPA and/or RF positive. MEFV mutations and/or autoantibody status allowed four PL arthritis patients to be distinguished: Group I (MEFV+), with younger age of onset, short duration attacks (<3 days), mainly located in the knee, more frequent non-articular manifestations (fever, pericarditis or abdominal pain) and good response to colchicine; Group II (autoantibody+) is older than group I, with the same frequency of short attacks, but the most affected joints were the wrists and small joints of hands: 48% met RA classification criteria during follow-up and were taking DMARDs; Group III (MEFV- and autoantibody-) was the most frequent (48%) and clinically heterogeneous group; 51% had attacks lasting >3 days, and 15 patients developed criteria of immune-mediated inflammatory, autoinflammatory or infectious diseases. Group IV (MEFV+ associated with pre-existing immune-inflammatory disease), was associated with very short-attacks, like groups I and II, superimposed or coincident with definite immune-inflammatory disease, including seropositive RA, with good response to colchicine.

Conclusions: Patients with PL arthritis can be classified in four groups according to the presence or not of MEFV mutations and ACPA/RF antibodies with a different clinical evolution and therapeutic response.

Keywords: MEFV gene; autoinflammatory disease; palindromic rheumatism; psoriatic arthritis; rheumatoid arthritis.