Baricitinib Attenuates Dermal and Pulmonary Fibrosis in a Bleomycin-Induced Murine Scleroderma Model: A Longitudinal High-Frequency Ultrasonography Study

Background: The bleomycin (BLM)-induced murine model is the most widely used experimental model of systemic sclerosis, yet fibrosis is conventionally verified only at sacrifice. We asked whether high-frequency ultrasonography (HFUS) can track dermal fibrosis in vivo and predict histopathology and whether the selective JAK1/2 inhibitor baricitinib is antifibrotic when started after fibrosis is established. Methods: Female C57BL/6 mice received subcutaneous BLM (10 mg/kg/day, five days weekly for four weeks) and were allocated to BLM alone, BLM plus baricitinib (10 mg/kg orally twice daily from day 14) or BLM plus vehicle (27 randomised; 23 completed the study). Dermal thickness was measured by HFUS on days 0, 14 and 28, and skin and lung histopathology and Col1a1/Col1a2 expression were assessed on day 28. Results: Day-28 HFUS correlated strongly with histopathological dermal thickness (r = 0.859, p < 0.001; partial r = 0.644 after controlling for group) with good intra-observer reliability (ICC 0.88). Baricitinib brought dermal thickness below the animals’ own baseline (−86.10 ± 81.55 µm) while it continued to rise in the other groups, and it reduced histopathological dermal thickness and modified Ashcroft scores. Conclusions: HFUS enables non-invasive longitudinal monitoring, and baricitinib reverses established dermal thickening.