Vitiligo Treatments: Therapeutic Modalities and JAK Inhibitors

Abstract and Introduction

Abstract

Vitiligo is a chronic autoimmune disease characterized by loss of pigment of the skin, affecting 0.5–2% of the population worldwide. It can have a significant impact on patients' quality of life. In recent years, there has been significant progress in our understanding of the pathogenesis of vitiligo. It is believed that vitiligo develops due to a complex combination of genetics, oxidative stress, inflammation, and environmental triggers. Conventional treatments include camouflage, topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids, phototherapy, and surgical procedures, with the treatment regimen dependent on the patient's preferences and characteristics. With increased understanding of the importance of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the pathogenesis of vitiligo, treatment has expanded to include the first US FDA-approved cream to repigment patients with vitiligo. This review summarizes our understanding of the major mechanisms involved in the pathogenesis of vitiligo and its most common available treatments.

Introduction

Approximately 0.5–2% of the population worldwide is affected by vitiligo, a chronic autoimmune disease characterized by the selective loss of melanocytes, resulting in depigmented patches of skin.^[1,2] The disease affects both males and females and all races and ethnicities.^[3] About 50% of patients show clinically apparent depigmented lesions before age 20 years, and nearly 70–80% before age 30 years, but the disease can manifest itself at any age.^[4] Although patients with vitiligo are not in physical pain, the psychological burden of the disease can be devastating, especially for darker-skinned individuals in whom depigmented areas are more easily detectable, particularly if present on visible areas of the skin. Thus, psychologically, vitiligo can lead to negative self-esteem, depression, social isolation, stigmatization, and overall decreased quality of life.^[3,5–10] Vitiligo is classified as either nonsegmental or segmental, as determined by the 2011 Vitiligo Global Issues Consensus Conference, and treatment and prognosis for both classifications vary.^[11] Until recently, there have been no US FDA-approved treatments for repigmenting vitiligo. Therapeutic options are based on several published consensus guidelines,^[12–15] but available options are not always effective, may have adverse effects, and disease often returns after discontinuing therapy. Additionally, acral areas, such as the hands and feet, are notoriously difficult to repigment with conventional methods compared with areas such as the face and trunk.^[16] In general, first-line treatment consists of topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs), second-line therapies consist of phototherapy and systemic corticosteroids, and third-line treatment consists of surgical procedures and depigmenting therapy,^{[14,15,17–20]} although an element of personalization must be kept in mind when determining a treatment approach. There is a strong need for targeted, safe therapies that are effective and long-lasting, and this goal is within reach given our increased knowledge of the specific pathways involved in the pathogenesis of vitiligo. For this narrative review, PubMed was searched using terms including, but not limited to, vitiligo pathogenesis, vitiligo treatment, and the relevant vitiligo treatment modalities included in this article (TCSs, TCIs, oral corticosteroids, phototherapy, surgical treatment, depigmentation therapy, minocycline, methotrexate, azathioprine, levamisole, apremilast, Ginkgo biloba (GB), Polypodium leucotomos (PL), and topical/oral Janus kinase (JAK) inhibitors). This paper aims to provide an overview of the pathogenesis of vitiligo and a comprehensive review of the therapeutic options available for vitiligo.