The ultimate effect of estrogen signaling on a tissue largely depends on the relative expression of estrogen receptors (ER) α and β. The latter are members of the nuclear receptor family of transcription factors. They are involved in the formation of a multi-protein complex and can form homo/heterodimers that upon activation, they move into the nucleus to bind with their coregulatory proteins. Through the binding to specific ER response element regions, they control the transcription of specific target genes. This is the genomic effect of ER. These receptors are produced by ESR1 and ESR2 genes, located on chromosomes 6 and 14, respectively. ERα and ERβ are

Background Vitiligo is a long‐standing progressive autoimmune disease with depigmented macules/patches with significant psychological morbidity to the patients. From being one of the most poorly understood diseases in the past, there has been a rampant advance in determining the molecular and genetic factors influencing the disease process. More light has been shed on the complex intracellular environment and interplay between innate and adaptive immunity. Numerous cytokines and signaling pathways have been associated with disease pathogenesis in the recent past. Objective The aim of this review the efficacy of biologic and targeted therapeutics in vitiligo. Methods A detailed literature search was conducted on databases like PubMed, COCHRANE Central, EMBASE and Google Scholar using keywords—“biologics,” “vitiligo,” “treatment,” “repigmentation,” “JAK inhibitors,”, “TNF‐ꭤ inhibitors,” and “IL17/23 inhibitors,” Relevant studies and review articles in English were analyzed in detail and report was written. This article aimed at a comprehensive review of all the biologicals and newer targeted therapeutics tried in vitiligo and their efficacy with an insight into the potential complications arising as a result of the therapy. Results Most conventional vitiligo treatment modalities are restricted to generalized nonspecific immunosuppressants like topical and oral corticosteroids, calcineurin inhibitors, phototherapy, and surgical modalities. There have been reports and studies on the usage of biologicals in treating vitiligo. JAK inhibitors have shown good efficacy in vitiligo; however, it lacks substantial evidence in the form of randomized control trials. Similarly, the use of targeted therapeutics in treating vitiligo is substantiated by limited evidence and requires more randomized trials for further evidence. Conclusion JAK inhibitors have shown promising results and good tolerability; Adjuvant phototherapy can achieve a superior response compared to monotherapy. Though TNF‐ꭤ has been tried in a few cases, it is best used if vitiligo is present in association with other chronic autoimmune diseases for which it is indicated. More in vitro studies and clinical research are required to understand the pathogenesis clearly, and therapy has to be targeted at specific pathways for a better approach toward vitiligo. Treatment aimed at induction and differentiation of melanocytes may be added to achieve faster repigmentation.