Clinical and laboratory characterization of patients with localized scleroderma and response to UVA‐1 phototherapy: In vivo and in vitro skin models

BACKGROUND/PURPOSE: Localized scleroderma (LS) is a rare disease leading to progressive hardening and induration of the skin and subcutaneous tissues. LS is responsive to UVA‐1 phototherapy, though its exact mechanism of action dermal fibrosis is yet to be fully elucidated. We aimed to investigate the molecular changes induced by UVA‐1 rays in human primary fibroblasts cultures. METHODS: A total of 16 LS patients were treated with medium‐dose UVA‐1 phototherapy. At baseline, during and after therapy, Localized Scleroderma Assessment Tool, Dermatology Life Quality Index and lesions' staging and mapping were performed along with high‐frequency ultrasound (HFUS) examination for dermal thickness assessment. Gene expression analysis for 23 mRNA transcripts, in vitro UVA‐1 irradiation and viability tests were realized on lesional fibroblasts' primary cultures, before and 3 months after therapy. RESULTS: The dermal thickness, the LoSCAT and the DLQI progressively decreased starting from the last phototherapy session up to the 6 and 9 month follow‐ups (−57% and −60%, respectively). Molecular gene analysis (rt‐PCR) revealed that UVA‐1 phototherapy exerts multiple effects: the activation of specific anti‐fibrotic pathways (e.g., overexpression of CTHRC1 and metalloproteases 1, 2, 7, 8, 9, 12, suppression of TIMP‐1), the downregulation of peculiar pro‐fibrotic pathways (e.g., downregulation of TGF‐ß, TGF‐ßrII, Grb2, SMAD 2/3, TNRSF12A, CTGF) through a significant overexpression of IL‐1ß; the stabilization of collagen synthesis acting on genes COL1A1, COL3A1, COL8A1, COL10A1, COL12A1. CONCLUSION: UVA‐1 phototherapy adds significant benefits in local tissue remodeling, rebalancing the alteration between pro‐fibrotic and anti‐fibrotic pathways; these changes can be well monitored by HFUS.