Neutropenia and Felty Syndrome in the Twenty-First Century: Redefining Ancient Concepts in Rheumatoid Arthritis...

Objectives: To describe the frequency of neutropenia and Felty syndrome in patients with rheumatoid arthritis (RA) attended in routine clinical practice. Methods: We selected by randomization a sample of 270 RA patients attended from January 2014 to November 2022. Demographic, clinical, and neutropenia-related variables were collected from the electronic medical records. Neutropenia was defined as having an absolute neutrophil count (ANC) of less than 1500/mm³ once, and acute if it persisted for <3 months. Felty syndrome was defined as RA-related neutropenia, rheumatoid factor (RF) and/or anti citrullinated protein antibody (ACPA) positivity. Results: We found 50 patients who had at least one neutropenia episode, with an incidence of 18.5% (14.0-25.6%). Most were women, with age (mean, p25-p75) at the time of neutropenia of 61.5 (57.4-69.3) years, 85% RF+ and 76% ACPA+. The demographic and RA characteristics of patients with and without neutropenia were very similar, except for sex: most patients with neutropenia were women. The 50 patients had 99 episodes of neutropenia; 59% were acute. The lower ANC was 1240 (1000-1395) mm³, and most of the episodes were mild (74%). In 32% of cases, there was other cytopenia. The RA activity measured by DAS28 in patients with neutropenia was low, at 2.18 (1.75-2.97). A total of 82 of 99 neutropenia episodes were related to DMARDs, 60% to Anti-IL6 drugs in monotherapy, 13% to RA activity, 3% to infectious diseases and 1% to hematologic malignancy. There were five (1.8%) cases with Felty syndrome, but only one woman with the classic combination of RA, positivity of autoantibodies (RF and ACPA), neutropenia and splenomegaly. Conclusions: In the 21st century, neutropenia in RA patients is most commonly related to biologics, mostly IL6 inhibitors and methotrexate. Episodes are mild, acute, with low RA activity, and associated with severe infections in few cases. Felty syndrome is rare.