¹LKH-Univ. Klinikum Graz, Rheumatologie und Immunologie, Graz

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Background: Systemic sclerosis (SSc) is a chronic autoimmune disease in which inflammatory, autoimmune and vasculopathic changes can occur due to a disturbed interaction between vessels, immune cells and fibroblasts. The vas t majority of patients with SSc (> 95%) have Raynaud's phenomenon (RP) and every second patient develops digital ulcers (DUs). There is little evidence of pharmacological therapy to DUs. PDE-5 inhibitors, iloprost and endothelin receptor antagonists can be used for therapy or prevention. DUs do not only have a significant impact on quality of life, but also represent a risk factor for infections, including gangrene and osteomyelitis.

Main symptom when the disease manifests itself: This case concerns a woman born in 1979, who suffers from SSc with limited skin involvement since 2000. Initially, she presented with RP, skin thickening on the fingers and foci of calcinosis cutis.

Diagnostics: Immunology testing revealed highly positive U1-RNP antibodies, with no signs of internal organ involvement.

Therapy: The patient initially received immunomodulatory therapy with methotrexate (MTX) and a calcium channel blocker (lercanidipine), as well as regular infusions of iloprost. Despite the initiated therapy, DUs developed, requiring regular antibiotic treatments. Even under additional therapy with a PDE-5 inhibitor (sildenafil) and the administration of bosentan, the patient continued to have recurrent DUs. Due to the leukopenia under therapy with MTX and later with abatacept and the patient’s refusal of rituximab, an off-label treatment with the JAK inhibitor (JAKi) filgotinib was started. This led to an improvement in the DUs, which healed completely over time. The skin was also in a stable condition and the internal organs showed no signs of activity.

Further course: At the last follow-up examination, the SSc Activity Score was 0 points. After exhausting pharmacological therapies according to the current EULAR guidelines and non pharmacological measures such as occupational therapy and paraffin baths, the patient received successful off-label therapy with the JAKi filgotinib for refractory DUs. There are individual case reports in the literature on the use of JAKi in SSc demonstrating their successful use in patients with pulmonary manifestations such as SSc associated interstitial lung disease (SSc-ILD) and joint involvement. In addition, some case reports indicate that JAKi may improve skin involvement, as measured by the modified Rodnan skin score (mRSS), as well as DUs. Currently, there are no formal recommendations for therapies outside the three established drug classes for the treatment of DUs in SSc, yet JAKi may represent a promising alternative treatment option. In this case, JAKi therapy led to a successful healing of the DUs. The comparatively low quality of the available evidence for JAKi in DUs in SSc emphasises the need for further future studies.

Literatur

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