A significant proportion of patients with discoid lupus erythematosus (DLE) experience joint pain, yet its underlying pathomechanism remains unclear. Recent ultrasound studies in systemic lupus erythematosus (SLE) patients indicate synovitis in up to 90%, even in clinically silent cases, with interferon-mediated immune responses implicated in joint inflammation. This study aimed to investigate joint pathology in DLE, focusing on synovitis and its immunological profile. We analyzed 23 patients with histologically confirmed DLE and joint pain, all treated for ≥ 5 months with prednisone (≤ 10 mg/day) and hydroxychloroquine (HCQ, 200 mg/day). Ultrasonographic assessment (24 joints per patient) was performed using power Doppler (PD) ultrasonography, with synovitis graded using the OMERACT-EULAR PDUS synovitis score. Serum levels of 37 cytokines were measured via Bio-Plex Pro™ Human Inflammation Panel (37Plex). Synovitis (OMERACT-EULAR score ≥ 1) was identified in 30% (7/23) of DLE patients, with minimal (grade 1) synovitis in six cases and moderate (grade 2) synovitis in one. Patients with synovitis had significantly higher levels of IFN-α2, IFN-γ, MMP-1, MMP-3, sTNF-R1, and sTNF-R2 (p <
0.05), more painful joints, and poorer response to HCQ treatment (71.4% vs. 25% non-responders). Joint pain in DLE may result from synovitis, with an interferon-mediated immune response contributing to inflammation. Patients with synovitis exhibited elevated interferon levels and a worse response to HCQ therapy. These findings suggest a shared pathogenic mechanism between DLE and SLE-related arthritis, warranting further investigation into targeted therapeutic strategies.