UVA‐1 phototherapy as adjuvant treatment for eosinophilic fasciitis: in vitro and in vivo functional characterization

Abstract

Introduction Eosinophilic fasciitis (EF) is a rare autoimmune disease causing progressive induration of dermal, hypodermal, and muscularis fascia. The exact pathogenesis is yet to be fully understood, and a validated therapy protocol still lacks. We here aimed to realize a clinical-functional characterization of these patients.Materials and methods A total of eight patients (five males, 45 years average) were treated with adjuvant high-dose UVA-1 phototherapy (90 J/cm), after having received the standard systemic immunosuppressive protocol (oral methylprednisolone switched to methotrexate). Body lesion mapping, Localized Scleroderma Assessment Tool (LoSCAT), Dermatology Life Quality Index (DLQI), High-Resolution Ultrasound (HRUS) (13-17MHz), and ultra HRUS (55-70 MHz) were performed at each examination time taking specific anatomical points. Gene expression analysis at a molecular level and in vitro UVA-1 irradiation was realized on lesional fibroblasts primary cultures. ResultsThe LoSCAT and the DLQI showed to decrease significantly starting from the last UVA-1 session. A significant reduction in muscularis fascia thickness (À50% on average) was estimated starting from 3 months after the last UVA-1 session and maintained up to 12 months follow-up. Tissues was detected by HRUS. The UVA-1 in vitro irradiation of lesional skin sites cells appeared not to affect their viability. Molecular genes analysis revealed a significant reduction of IL-1ß and of TGF-ß genes after phototherapy, while MMPs 1,2,9 gene expression was enhanced.Comment These preliminary in vivo and in vitro findings suggest that UVA-1 phototherapy is a safe and useful adjuvant therapy able to elicit anti-inflammatory effects and stimulate tissue matrix digestion and remodeling at lesional sites.

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

“…29,31,36 Our experiments showed that in vitro UVA-1 irradiation performed with crescent doses and progressively longer irradiation times (range 10 s-20 min) does not affect the viability of lesional fibroblasts cultures (Table 1): these findings are in line with the behavior of lesional primary fibroblasts irradiated with UVA-1 rays 5,[11][12][13][24][25][26] and support the current consensus on the overall safety of the UVA-1 phototherapic approach. [3][4][5] In view of the complexity of the immunopathological mechanism underlying the scleroderma lesion, we chose to perform a direct gene expression assessed by RT-PCR, rather than a functional analysis, to investigate the main markers of fibrosis and anti-fibrotic pathways. Indeed, gene expression analysis makes it possible to estimate the metabolic activity of lesional fibroblasts in a given moment, as demonstrated by recent gene profiling and "transcriptomics" studies.…”

“…Localized scleroderma is still poorly studied at both epidemiological and laboratory levels, especially when compared with SSc. Actually, many patients receive late diagnosis or wrong management, exhibit long‐term corticosteroid side effects or develop functional‐aesthetical disabilities impacting life quality 1–5,23–26 . Nevertheless, it can be clinically difficult both to determine whether LS lesions are active, to define their peculiar stage and to assess the presence of subcutaneous damage 1–4,19 .…”

“…Skin ultrasound has received increasing attention for LS monitoring, in the last decades, 27–32 first with low‐frequency US (6–8 mHz), 27 then with medium frequency‐MFUS (9–15 mHz) 29 and recently with high‐frequency‐HFUS (>20 mHz) 5,27–29,37 . The available data on patients with LS 30–32,36,37 and with SSc‐LS association forms 24 point toward a greater sensitivity of HFUS in obtaining highly defined images.…”

“…A medium‐dose protocol was employed in all patients, i.e. : 36 consecutive sessions of 60 J/cm 2 , 3 to 4 times per week 3–5 . Skin was prepared in patients with phototype II with three preliminary sessions of low dose UVA‐1 (i.e., 30 J/cm 2 ) every 48 h. During phototherapy, patients were recommended to wear a pair of protective tanning eyewears.…”

“…Localized Scleroderma (LS) in its patchy or plaque form, also known as morphea, is a rare autoimmune disease characterized by an inflammatory process causing a progressive sclerosis of the dermis, with consequent involvement of the epidermis and the subcutis (i.e., deep morphea). [1][2][3][4][5] The exact pathogenetic mechanism is extremely complex…”