Dermatologic Presentation of Etanercept-Induced Lupus in Rheumatoid Arthritis

Abstract

Background Etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, is widely used in the management of inflammatory arthropathies. While effective in modulating inflammatory responses, TNF-α inhibitors are associated with rare paradoxical immune-mediated adverse effects, including drug-induced lupus erythematosus (DILE). Although systemic manifestations of DILE in the setting of TNF-α inhibitor use have been well-established in the literature, manifestations of cutaneous etanercept-induced lupus erythematosus (EILE) remain under-reported. 

Case We present the case of a 46-year-old male with a past medical history of seropositive rheumatoid arthritis (RA) who reported new onset pruritic, well-demarcated, confluent, erythematous plaques involving the distal left upper and left lower extremity in the course of treatment with etanercept. During the course of treatment, autoantibody testing identified elevated-titers for ANA, dsDNA, Ro/SS-A, and anti-histone antibodies, consistent with a diagnosis of DILE. Discontinuation of etanercept and initiation of alternative therapy led to marked improvement. A subsequent course of prednisone facilitated complete cutaneous recovery at one month following discontinuation. Subsequent labs revealed a decline in anti-histone antibodies, corroborating the diagnosis

Discussion and Conclusions A review of the literature using PubMed and Google Scholar from 1999 to 2025 identified only nine reported cases of cutaneous manifestations associated with EILE. By situating our case of cutaneous EILE within the context of existing literature, we delineate the consistent serologic and systemic findings, underscore the key cutaneous manifestations, and highlight the need for heightened awareness of DILE in patients receiving rheumatologic therapies, while highlighting management strategies.