Evaluation Safety ,Efficacy Baricitinib Plus Excimer Light Versus Excimer Light Alone in Non Segmental Vitiligo

Vitiligo is an acquired pigmentary skin disorder characterized by the absence of pigmentary cells from the epidermis that results in white macules and patches on the body. (1) The pathogenesis of vitiligo is unknown, but an autoim¬mune hypothesis prevails. (2, 3) CD8+ inflammatory damage induced by cytotoxic T cells is one of the key immune responses leading to depigmentation and destruction of melanocytes in vitiligo. (4-6) The IFN-γ - chemokine (CXCL9/10-CXCR3) axis, with its associated positive feedback loop, has been identified as a potential pathway in the initiation and progression of the immune response in vitiligo via inhibiting melanogenesis, inducing apoptosis of melanocytes, and further recruiting CD8+ T cells to the skin. (7-9) Janus kinases (JAKs) are a family of cytoplasmic tyrosine kinases (TYKs). (10) They aid cytokine-mediated signal transduction through the JAK/STAT pathway. (11) The key members of this unique tyrosine kinase family include JAK1, JAK2, JAK3, and TYK2. (12) The IFN-γ signaling is dependent on the JAK/STAT pathway. IFN-γ activates the JAK/STAT1 pathway, especially through JAK1 and JAK2. (13) This leads to the phosphorylation of STAT1, with subsequent transcription of IFNγ-induced genes, namely CXCL9 and CXCL10. (14) Given the role of JAK1 and JAK2 in the JAK/STAT pathway, IFN-γ signals can be blocked by inhibiting JAK1 or JAK2. (15) The treatment of vitiligo is generally and challenging, moreover, the goal of treatment is not only to halt disease progression, but promote repigmentation. (16) There are a variety of therapeutic possibilities including topical, systemic and surgical methods encompass grafting and transplantation. (17) The 308 nm excimer laser represents the latest alternative NB-UVB therapy for treating vitiligo. It's a gas laser that can emit a wavelength of 308 nm UVB produced by xenon and chlorine gases. (18) The effectiveness and safety of 308 nm excimer laser phototherapy are superior to that of NB-UVB phototherapy, which may be explained by the ability of the excimer laser to emit coherent pulses, as well as differences in phototherapeutic parameters, such as impulse frequency and intensity, therapy stimulating a deeper reservoir of melanocytes in hair follicles. (19) JAK inhibitors can block the IFN-γ signaling via the JAK-STAT pathway and thus have become an emerging treatment for vitiligo. (20) Based on clinical trials, the US Food and Drug Administration (FDA) approved topical Ruxolitinib 1.5%, a JAK 1 and 2 inhibitor, in patients 12 years of age or older for the treatment of non-segmental vitiligo. (21) In the treatment of vitiligo, a few published case reports, case series, and open-label studies have shown superior re-pigmentation rates in patients treated with JAK inhibitors, especially with concomitant ultraviolet or sun exposure. (22) Given IFN-γ signaling is specially mediated by JAK1 and JAK2, baricitinib, a newer JAK1 and JAK2 inhibitor, has been supposed to be effective in treating vitiligo. (23) The effectiveness of oral baricitinib in treating vitiligo has been reported in small case studies. (23-25) Some clinical studies have confirmed that the application of JAK inhibitors can have side effects, such as infection, malignancy, and major adverse cardiovascular events (MACEs). (26) Clinical disease screening of patients before the use of JAK inhibitors and continuous monitoring during their use are essential. (27) Topical administration of the drug results in improved drug delivery, fast onset of action, and the targeted distribution of the active medication to skin lesions while minimizing the safety concerns related to oral administration. Therefore, some experts believe that topical application show better effects and lower adverse reactions. (28, 29) Given the reported effectiveness of oral barcitinib in vitiligo as well as the successful results of topical forms of other JAK inhibitors, we expect that baricitinib would have similar effect if used topically.