Phototherapy in Scleroderma

Dermatol Ther (Heidelb) (2016) 6:519–553 DOI 10.1007/s13555-016-0136-3 REVIEW Phototherapy in Scleroderma John Hassani . Steven R. Feldman Received: June 27, 2016 / Published online: August 12, 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com ABSTRACT phototherapy in the treatment of scleroderma. Based on the limited studies available, 20–50 J/ Systemic and localized scleroderma are difficult to manage diseases with no accepted gold cm2 of UVA1 therapy 3–4 times a week for 30 treatments is recommended. standard of therapy to date. Phototherapeutic modalities for scleroderma show promise. A PubMed search of information on phototherapy for scleroderma was conducted. The information was classified into effects on pathogenesis and clinical outcomes. Studies on photopheresis were excluded. There were no randomized, double-blind, placebo-controlled Keywords: Morphea; Phototherapy; Scleroderma; UVA; UVB PUVA; INTRODUCTION: BACKGROUND ON MORPHEA/SCLERODERMA studies, and only three controlled studies. The vast majority of identified studies evaluated Scleroderma is a chronic autoimmune disease ultraviolet A1 (UVA1) phototherapy. More organ involvement. Cutaneous scleroderma is characterized by enhanced fibroblast activity rigorous studies are needed to evaluate associated with cutaneous, joint, and internal leading to hypertrophic dermal collagen. There are localized and systemic forms of scleroderma. Enhanced content To view enhanced content for this article go to http://www.medengine.com/Redeem/ C7E4F0600C13C58F. The localized forms include morphea and linear scleroderma. Localized scleroderma has a better prognosis and does not involve internal organs. J. Hassani (&) Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA e-mail: There are currently no curative treatments for scleroderma. Current treatments include S. R. Feldman Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA phototherapy. This review serves to provide immunosuppressants; intralesional, topical, and oral steroids; topical vitamin D; and insight into the use of phototherapy in the Dermatol Ther (Heidelb) (2016) 6:519–553 520 management of scleroderma. This article is UVA1 radiation increases collagenase [also based on previously conducted studies and known does not involve any new studies of human or animal subjects performed by any of the (MMP-1)] gene, mRNA, and protein expression by fibroblasts [5–9]. In mice models, UVA1 authors. radiation reduces fibroblast proliferation in a dose-dependent fashion [10, 11]. Additionally, modalities utilize specific tissue that has developed in some patients with skin disease. Various phototherapy modalities anti-inflammatory effects [1]. The longer the wavelength of phototherapy, the deeper in the dermis it penetrates [2]. Current phototherapeutic modalities being used for dermatoses include broadband ultraviolet B (UVB 290–320 nm), narrowband UVB (311–313 nm), excimer laser (308 nm), ultraviolet A (UVA 320–400 nm), ultraviolet A1 (UVA1 340–400 nm), (PUVA), and matrix metalloproteinase-1 week showed decreased hydroxyproline and collagen levels in a dose-dependent fashion wavelengths of the electromagnetic spectrum to disrupt the dysfunctional and pathologic possess the UVA1 radiation administered three times a PHOTOTHERAPY IN DERMATOLOGY Phototherapy as psoralen and UVA extracorporeal photochemotherapy. MECHANISM BEHIND PHOTOTHERAPEUTIC MODALITIES USED IN SCLERODERMA [11]. The quality of the collagen is altered after UVA1 therapy, as collagen appears less dense and smoother compared to before treatment [12]. Decorin (a proteoglycan component of connective tissue) mRNA levels are lower in lesional scleroderma versus non-lesional skin, and decorin levels are increased after UVA1 phototherapy [13]. Transforming growth factor beta (TGF-b) protein levels (TGF-b is profibrotic) are inversely correlated with decorin levels. On the other hand, another study showed that after UVA1 phototherapy, decorin was decreased in the upper to middle dermis, although decorin slightly increased in the papillary dermis [14]. In patients, UVA has been shown to reduce collagen I, collagen III, and TGF-b and increase interferon-c [9]. UVB radiation increases alpha melanocyte-stimulating hormone (a-MSH) receptor synthesis in keratinocytes and melanocytes [15]. Human fibroblast dermal cultures treated with a-MSH demonstrated an increase in MMP-1 mRNA, indicating that A common theory behind the mechanism of phototherapy in scleroderma is that light is a-MSH may be one of UVB’s mediators of anti-fibrosis [16]. converted to chemical energy resulting in the The source of the mediators that contribute increase of reactive oxygen species or singlet oxygen production, which can modulate the to the reduction in sclerosis comes mostly from the dermis. Subsequently, certain parts of the expression of cytokines [3, 4]. Ultraviolet radiation includes UVA and UVB therapy, with dermis may be impacted more than others. An image analyzer showed a greater reduction in UVA1 studied the most. UVA1 can have an collagen fibers in the upper and middle dermis output categorized as low (10–30 J/cm2), moderate (40–70 J/cm2), or high (up to 130 J/ and less reduction in the lower dermis [12]. In 18 patients treated with UVA1, the MMP-1 level cm2). was higher in the papillary layers and lower in Dermatol Ther (Heidelb) (2016) 6:519–553 521 the reticular layers [17]. The anti-fibrotic effects after in vitro irradiation with UVA1 [8]. Thus, of phototherapy may not come exclusively the SSc fibroblasts may be more susceptible to from the dermis. Samples taken 18 h after the final UVA1 treatment in a set of patients phototherapy-induced oxidative stress than normal fibroblasts [8]. Additionally, heme showed an increase in interstitial collagenase in the upper layer of keratinocytes, oxygenase-1 may reduce fibrotic conditions via TGF-b [22]. UVA1 may play a role in melanocytes, and endothelial cells [5]. angiogenesis. In patients exposed to UVA1 Evidence supports the regimen of multiple UVA1 therapy sessions a week. The phototherapy for 14 weeks, there was an increase in CD34? cells and an increase in anti-sclerotic effects of a single exposure of UVA1 effects are typically seen to last less than vascular endothelial growth factor (VEGF) [23]. The neuroendocrine system may be involved, as 1 week. In human skin, mRNAs of type I and III UVA1 therapy decreases dermal expression of procollagen were decreased and MMP-3 was increased after 3 days of a single UVA1 dose neuron-specific enolase, which correlated with softening of skin lesions in patients with SSc [18]. MMP-1 and MMP-3 were upregulated for 3 to 5 days, while procollagen levels were with acral lesions [24]. UVB phototherapy results in DNA dama (...truncated)