The genetics of pediatric cutaneous autoimmunity: The sister diseases vitiligo and alopecia areata.

Autoimmunity, the reaction of the host against self, is a complex pattern of immunologic response that allows the immune system to react to "normal" tissue. Many such diseases exist in the skin, but in particular, two stand out as visible manifestations of autoimmune cutaneous attack. These are vitiligo, the immune attack on the melanocyte, and alopecia areata, the immune attack of the hair unit. These two illnesses include the prototypes of "simple" attacks on specific components of the skin. Other such illnesses are psoriasis—a complex series of immunologic responses resulting in a characteristic pattern of keratinocyte hyperproliferation—and lichen planus, which is similarly associated with a typical cutaneous skin disease pattern, but these will not be included in this review. In comparison, autoimmune polyendocrinopathies have defined pathways of disease based on single-gene mutations that can result in a variety of autoimmune skin features including vitiligo and alopecia areata. This contribution reviews known patterns of autoimmunity in childhood skin disease with a particular focus on single-gene disorders where they exist, and the more common multifactorial genes that contribute to this breach of the immune system's regulatory checks and balances. Genetic mechanisms that will be covered include innate and adaptive immunity, major histocompatibility complex II class associations, genetic polymorphisms, and major histocompatibility complex I class associations that bridge autoinflammatory and autoimmunity states, as well as alterations in oxidative metabolism promoting tissue destruction. End-organ tissue destruction appears to occur via interferon gamma and cytotoxic mediated activity and is a promising new therapeutic target. Janus kinase inhibitors also have the benefit clinically of both affecting the immune cascade at the cytotoxic T cell level and allowing triggering of melanocyte and hair follicular activity through the signal transducer and activator of transcription pathway, representing an attractive therapeutic with dial activity, among other cytokines implicated in end-organ destruction. Transplacental autoimmunity will not be covered herein. Greater insight into mechanisms of pediatric cutaneous autoimmunity in vitiligo and alopecia areata has yielded better therapeutic options and interventions. Understanding the basis of autoimmune triggering in our patients, that is, personalized medicine, may allow for targeted therapeutics with a goal of induction of remission, regeneration, or rejuvenation of the end-organ with the least toxic side effect profile. [ABSTRACT FROM AUTHOR]