• Disease pathogenesis, therapeutics and the outcomes of genetic and non-genetic elements in vitiligo: An Overview
  • Sara Seyed Shazileh,1,* Mohaddeseh Jafarnia Kalansara,2 Seyed Mohammad Moshtaghioun,3
    1. Department of Biology, Faculty of science, Yazd University, Yazd, Iran
    2. Department of Biology, Faculty of science, University of Mohaghegh Ardabili, Ardabil, Iran
    3. Department of Biology, Faculty of science, Yazd University, Yazd, Iran


  • Introduction: Vitiligo is a long-standing progressive autoimmune disorder that's characterized by the absence of pigment within the skin and therefore the loss of melanocytes. Melanocytes are found within the basal layer of the epidermis in many tissues involves the skin, hair follicles, eyes, inner ear, bones, heart, and brain, and along with the keratinocytes form the epidermic unit, whose main perform is to provide and distribute melanin by a complex method known as melanogenesis. Melanogenesis is decided genetically however is influenced by many intrinsic and extrinsic factors. The intrinsic factors are free by close cells, as well as keratinocytes, fibroblasts, inflammatory, neural, and endocrine cells, and the extrinsic elements, encompass ultraviolet radiation and medicines. Nowadays there has been a rampant advance in determining the molecular and genetic factors influencing the disease process and the relationship between several cytokines and signaling pathways with the pathogenesis of the disease has been determined. An autoimmune hypothesis predominates and is supported by several factors: its association with other autoimmune diseases, high levels of antibodies against melanocytes found in 10% of patients with vitiligo, susceptibility loci associated with vitiligo in genome-wide association studies that encode immunomodulatory proteins, and lastly, an inflammatory infiltrate seen at the periphery of active lesions. In biochemical theory, damage to melanocytes is due to an imbalance in oxidative stress. Higher levels of hydrogen peroxide in vitiligo patients and increased superoxide dismutase activity support this theory. Another hypothesis is the melanocytorrhagy theory, which proposes that defective cell adhesion leads to detachment and transepidermal loss of melanocytes with exposure to autoantigens and activation of the immune system leading to melanocyte injury. Eventually, the convergence theory states that the presence of a combination of several pathways causes vitiligo, including genetic background, sensitivity to environmental changes, altered epidermal microenvironment, intrinsic melanocyte defect, and autoimmune response. Clinically, vitiligo appears as achromic patches that increase in number and area over time. Therapy strategies aim to halt the disease, achieve repigmentation, and prevent a recurrence.
  • Methods: A thorough search was done using the terms "vitiligo," "autoimmune"', "oxidative stress", "repigmentation," "JAK inhibitors," "TNF-α inhibitors," and "IL inhibitors" on databases including Google Scholar, Medline, and PubMed. The study was created after a thorough analysis of pertinent English-language papers and review articles. This article sought to provide a thorough analysis of all biological and more recent targeted treatments used to treat vitiligo, as well as their effectiveness and any potential side effects.
  • Results: Vitiligo is a multifactorial ailment with a tricky interaction among various factors regarding genetic and non-genetic elements along with non-immunological and immunological elements. The remedy modalities in vitiligo have frequently been nonspecific and generalized like topical immunosuppressive, phototherapy, surgical techniques with modest efficacy, and potential adverse effects. Owing to higher information on the pathophysiology, there's the viable emergence of more modern unique centered treatment options aimed toward proscribing ailment development and attaining repigmentation with a good safety profile.
  • Conclusion: Despite recent significant advancements in our understanding of vitiligo, its pathophysiology and causation are still unknown. There are still questions concerning what ultimately leads to the destruction of melanocytes, and further research is required to fully understand the etiology of vitiligo. A better knowledge of pathophysiology has led to the development of newer, more focused medicines with a high safety profile that attempts to slow the progression of the disease and achieve repigmentation. JAK inhibitors are the only class to date with outcomes that are both promising and well tolerated; but, like any immunosuppressant, they carry the danger of reawakening latent infections and a few systemic side effects. Comparing adjuvant phototherapy to monotherapy can result in a better response. Despite TNF-α inhibitors have been utilized in a few cases, it is most effective when vitiligo is present in conjunction with other chronic autoimmune disorders for which it is prescribed. Additionally, before beginning treatment, patients should be informed of the possibility of their condition getting worse or developing de novo vitiligo. Also, IL inhibitors have not been very good at achieving the desired response. Numerous new therapies are under development, and the majority of available information about them is provided by case studies or series. However, more randomized controlled trials are required to better evaluate their effectiveness.
  • Keywords: Vitiligo, Autoimmunity, TNF- α inhibitors, JAK inhibitors