Vitiligo ( VIT-ih-LY-goh) is a chronic autoimmune disorder that causes skin to lose pigment (specifically melanin, which gives the skin color) in patches that vary in size and can appear anywhere on the body. The development of vitiligo is linked to aberrant attachments between melanocytes (which produce melanin) and laminins, an extracellular protein. The disorder is thought to be caused by immune system changes with potential genetic factors. Often first appearing by young adulthood, it may be triggered by environmental factors, sun or chemical exposure, stress, and physical trauma. The most common form tends to affect more skin over time, with potential treatments including topical medications and light therapy. In antiquity, the disorder was often conflated with leprosy, an infectious disease. Some public figures have had vitiligo, such as the singer Michael Jackson, who obscured his condition until it affected his entire body.
Signs and symptoms 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. Additionally, the hair of affected areas can turn white or gray due to the loss of melanin. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders. Vitiligo also appears in other mammals, being conspicuous for instance on Arabian horses.
Causes The development of vitiligo is linked to aberrant attachments between melanocytes (which produce melanin) and laminins, a kind of glycoprotein. When the basement membrane (the fibrous layer between cells and adjacent connective tissue) becomes enriched in laminin-332, melanocytes attach to that protein instead of the normal laminin-211 (via an integrin receptor instead of dystroglycan). Rather than disappearing, melanocytes appear to dedifferentiate and thus lose the ability to produce pigment, altering the actin cytoskeleton of affected cells. Melanocyte loss may also be caused by the activation of the signaling pathway formed by Janus kinases (JAKs) and signal transducer and activator of transcription proteins (STATs), being triggered by T cells and creating a positive feedback loop with interferon-gamma (IFN-γ) chemokines (a form of cytokine signaling protein) secreted by keratinocytes, the primary cell type of the epidermis. According to one study, segmental vitiligo (SV) is linked to the dysfunction of sympathetic nerves and demonstrates increased adrenoceptor responses in the affected areas as well as three times higher local blood flow. Meanwhile, a blood flow increase of about 1.5 times occurs in the more common nonsegmental vitiligo (NSV). The disorder has occurred in recipients of bone marrow and lymphocytes from donors with vitiligo.
Immune system Strong statistical evidence links vitiligo to changes in the immune system. It is thought to be caused by the immune system attacking and destroying melanocytes. Variations in genes expressed in immune cells or melanocytes have been associated with the disorder. A genome-wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. One of them is the gene that encodes the protein tyrosinase, a melanocyte enzyme that catalyzes melanin biosynthesis and is a major autoantigen in generalized vitiligo. It has been 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 and thus triggers an immune response. Additionally, artificial sweeteners such as sucralose can make gut bacteria more aggressive, potentially damaging pigment-producing cells. 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.
Environmental and physical factors Susceptibility to vitiligo appears to be affected by region, especially early in life (e.g. a lack of exposure to microbes weakening the immune system). Most cases seem to start before the age of 20. An event like a sunburn, exposure to toxins, stress or emotional distress can trigger and/or exacerbate the condition. Existing cases of vitiligo may also be aggravated by temperature changes (causing dryness or sweating), poor hydration, or unprotected sun exposure. Skin depigmentation can occur at the site of physical trauma, 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. The phenomenon occurs in a third of patients with NSV but is rarely seen in SV. Vitiligo may be a multifactorial disease, with environmental factors triggering preexisting genetic susceptibilities.
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