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Introduction Pansclerotic morphea (PSM) is a very rare and severe disorder within the scleroderma spectrum, characterized by inflammation and progressive fibrosis of the skin and underlying tissues, leading to joint contractures, chronic ulcers, and high disability. Conventional immunosuppressive therapies and autologous stem-cell transplantation (ASCT) often fail to attenuate disease progression, and the prognosis remains poor. Preliminary data implicate Janus kinase (JAK) – STAT signalling in PSM pathogenesis, suggesting ruxolitinib, a JAK 1/2 inhibitor, as potential therapeutic option [N Engl J Med. 2023 Jun 15;388(24):2241-2252].Material and Methods We report the case of a young man diagnosed with PSM in March 2020 at the age of 17, who presented with rapidly progressive diffuse induration of the trunk and limbs (face spared), confirmed by histopathology.Results Initial treatment with corticosteroids and methotrexate yielded limited benefits. Mycophenolate mofetil (August 2020), followed by sequential trials of rituximab (March 2021), tocilizumab (October 2021), abatacept (May 2022), and cyclophosphamide (May 2023), each over a minimum of six months, failed to achieve disease control. During this time, the patient developed extensive skin thickening, disabling joint contractures, and chronic ulcers, complicated by recurrent infections and progressive loss of function. Given the refractory disease course, ASCT was performed in September 2023 ( figure 1). A modest clinical improvement was noted over the next months, including partial ulcer healing. By March 2024 (six months post-ASCT), approximately 50% of ulcer surface area had healed, but improvement plateaued, and significant lesions and functional limitations persisted (figure 1). In January 2025 ruxolitinib was initiated to target STAT4-mediated fibroblast activation implicated in PSM. The response was rapid and sustained. By July 2025, approximately 90% wound healing was achieved, alongside improvements in joint mobility (figure 1). Ruxolitinib was well tolerated, with no significant adverse effects and stable laboratory and organ function throughout follow-up.Conclusions This case refractory to every available treatment modality highlights the potential of JAK inhibition with ruxolitinib in PSM, resulting to substantial and sustained wound healing and functional recovery. These findings align with emerging evidence on STAT4-driven autoinflammation in PSM, suggesting that targeted therapy may represent a promising strategy for severe, treatment-resistant disease.Figure 1. Clinical images show fibrosis and ulceration; 1.1 before autologous stem-cell transplantation (ASCT); 1.2. six months post-ASCT (limited response); and 1.3. six months post-Ruxolitinib treatment (significant improvement) in a) upper body; b) right and left hand-palm; c) right and left calf d) right and left medial malleolus.Abstract P.211 Figure 1