Immune dysregulation and inflammation causing hypopigmentation in post kala-azar dermal leishmaniasis: partners in crime?

Post kala-azar dermal leishmaniasis (PKDL), a heterogeneous dermal sequela of visceral leishmaniasis (VL), is challenging in terms of its etiopathogenesis. Hypopigmentation is a consistent clinical feature in PKDL, but mechanisms contributing to the loss of melanocytes remains poorly defined. Like other hypopigmentary dermatoses - for example, vitiligo, psoriasis, and leprosy - the destruction of melanocytes is likely a multifactorial phenomenon, key players being immune dysregulation and inflammation. This review focuses on immunological mechanisms responsible for the 'murder' of melanocytes, prime suspects at the lesional sites being CD8+ T cells and keratinocytes and their criminal tools being proinflammatory cytokines, for example, IFN-gamma, IL-6, and TNF-alpha. Collectively, these may cause decreased secretion of melanocyte growth factors, loss/ attenuation of cell adhesion molecules and inflammasome activation, culminating in melanocyte death.