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.

Results: The LoSCAT and the DLQI showed to decrease significantly starting from the last UVA-1 session. A significant reduction in muscularis fascia thickness (-50% 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.

Figure 1

Clinical mapping was performed before, during, and after UVA‐1 adjuvant phototherapy for cutaneous signs of eosinophilic fasciitis (a) and ultrasound mapping (b) for dermal, hypodermal, and fascial examination at established repere points

Figure 2

Baseline ultra‐high‐resolution ultrasound (uHRUS) of two repere points of the tight‐T (a) and abdomen‐Ab (b), in a 35‐year‐old patient with eosinophilic fasciitis: the muscularis fascia (MF), usually not visible as a linear acoustic interface, is detectable as multiple parallel echoes ranging from 1 to 1.5 mm, whereas the dermal (D) and hypodermal (HD) layers appear hyperechogenic due to the tissue‐reactive fibrosis. Hematoxylin and eosin staining of traditional incisional biopsy (a) reaching the muscularis fascia and muscular tissue dermal, where eosinophils are visible at higher magnification; microbiopsy obtained with an 18G (<2 mm inner diameter) needle (b)

Figure 3

Ultrasound mapping realized by 50 MHz and 15 MHz of three repere points (abdomen, Ab; forearm, F; and thigh, T) was performed in a 45‐year‐old patient with eosinophilic fasciitis at baseline (a) and 3 months post‐UVA‐1 adjuvant phototherapy (t ₅) (b): the thickness of the muscularis fascia (MF) is significantly reduced at t ₅ in all repere points, whereas the dermis (D) and hypodermis (HD) is morphologically unaltered

Figure 4

Ultrasound mapping realized by 15 MHz of two repere points (forearm, F and thigh, T) performed in a 40‐year‐old patient at baseline (a, c) and 3 months post‐UVA‐1 adjuvant phototherapy (t ₅) (b, d): the thickness of the muscularis fascia is significantly reduced at both F and T repere point

Figure 5

Summary of the t ₀–t ₇ assessments of average dermal value, hypodermal, and muscularis fascia thickness by high‐frequency ultrasound (a), Localized Scleroderma Cutaneous Assessment Tool (LoScat) (b), and of the Dermatology Life Quality Index (DLQI) (c)

Figure 6

Human lesional fibroblasts harvested at baseline and irradiated in vitro with crescent UVA‐1 doses, imaged at different magnifications (a), and tested for viability (MTT) (b) before and after 24, 48, and 72 hours; healthy controls are also shown (b). Normalized expression quantified by real‐time PCR of interleukin‐1β (IL‐1β) and metalloproteinase 1 encoding genes, from lesional tissue specimens obtained before (pre) and after (post) 3 months UVA‐1 phototherapy in patients with eosinophilic fasciitis; control patients matched for age, sex, and body site (ctr)