Vitiligo

Vitiligo (/ˌvɪtɪˈlaɪɡoʊ/ VIT-ih-LY-goh) is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure, and susceptibility to it may be affected by regional environmental risk factors, especially early in life. Treatment options include topical medications, light therapy, surgery and cosmetics. The condition causes patches of a light peachy color of any size, which can appear on any place on the body; in particular, nonsegmental vitiligo, the common form, tends to progress, affecting more of the skin over time. Vitiligo spots on the skin can also vary in pigmentation over long periods, although they will stay in relatively the same areas.

The only sign of vitiligo is the presence of pale, patchy areas of depigmented skin, which tend to occur on the extremities. Some people may experience itching before a new patch appears. The patches are initially small, but often grow and change shape. When skin lesions occur, they are most prominent on the face, hands, and wrists. The loss of skin pigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus. Some lesions have increased skin pigment around the edges. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders.

Although multiple hypotheses have been suggested as potential triggers that cause vitiligo, studies strongly imply that changes in the immune system are responsible for the condition. Vitiligo has been proposed to be a multifactorial disease with genetic susceptibility and environmental factors both thought to play a role. It is hypothesized that damaging environmental factors can disrupt redox reactions necessary for protein folding, so skin cells may initiate the unfolded protein response which releases cytokines, thus mounting an immune response.

The National Institutes of Health states that sometimes an event, like a sunburn, emotional distress, or exposure to a chemical, can trigger or exacerbate the condition. Skin depigmentation in particular areas in vitiligo can also be triggered by mechanical trauma: this is an example of the Koebner phenomenon. Unlike in other skin diseases, this can be caused by daily activities, especially chronic friction on particular areas of the body.

Variations in genes that are expressed in the immune cells or in the melanocytes have both been associated with vitiligo. It is thought to be caused by the immune system attacking and destroying the melanocytes of the skin. A genome-wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. One of them is the TYR gene that encodes the protein tyrosinase, which is an enzyme of the melanocytes that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo.

Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimoto's thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addison's disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease.

Among the inflammatory products of NLRP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β and interleukin-18 are expressed at high levels in people with vitiligo. In one of the mutations, the amino acid leucine in the NALP1 protein was replaced by histidine (Leu155 → His). The original protein and sequence are highly conserved in evolution, and are found in humans, chimpanzees, rhesus monkeys, and bush babies. Addison's disease (typically an autoimmune destruction of the adrenal glands) may also be seen in individuals with vitiligo.

Numerous whole-exome sequencing studies have demonstrated that vitiligo is associated with polymorphisms in genes involved in the response to oxidative stress, such as CAT, SOD1, SOD2, SOD3, NFE2L2, HMOX1, GST-M1, or GST-T1, supporting the association of elevated levels of reactive oxygen species in melanocytes with the induction of an autoimmune response.