Background: Rheumatoid arthritis (RA) can manifest with extra-articular involvement affecting various organs and systems. The skin is the most commonly involved organ, with the classic manifestation being subcutaneous rheumatoid nodules (RNs), typically found in pressure-exposed areas of the skin. Accelerated nodulosis (AN) is considered a paradoxical effect of methotrexate (MTX) therapy and must be distinguished from classic RNs.

Case report: We report one diagnosed clinical case of seropositive RA patients who, during MTX therapy, experienced the rapid onset of RNs in multiple and unusually exuberant sites, and four suspected cases.

Conclusions: The development of unusually large RNs and/or their rapid appearance in multiple sites during MTX therapy, particularly in patients with low to moderate disease activity, should raise clinical suspicion for AN.