Vitiligo

Classification and external resources
Non-segmental vitiligo of the hand.
ICD-10	L80
ICD-9	709.01
OMIM	193200
DiseasesDB	13965
MedlinePlus	000831
eMedicine	derm/453
MeSH	D014820

Vitiligo /ˌvɪtɨˈlaɪɡoʊ/ is a condition that causes depigmentation of parts of the skin. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress, neural, or viral causes.^[1] The incidence worldwide is less than 1%.^[2] There are two main types of vitiligo: idiopathic and chemical.^[3] Most vitiligo is idiopathic; however, in cases where it is triggered by skin bleaching or other substances, it is said to be chemical.

Signs and symptoms

Vitiligo on lighter skin

Vitiligo on darker skin

The most notable symptom of vitiligo is patchy areas of skin that have lost their pigment which tends to occur on the extremities.^[4][5] Although patches are initially small, they often grow and change shape.^[1][4] When skin lesions occur, they are most prominent on the face, hands and wrists.^[4][5] The loss of skin pigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus.^[4][5] Some lesions have increased skin pigment around the edges.^[6] Patients who are stigmatized for their condition may experience depression and similar mood disorders.^[7] A black light (also referred to as a UVA light, Wood's lamp, or simply ultraviolet light) can be used in the early phase of this disease for identification and to determine effectiveness of treatment. Skin with vitiligo, when exposed to a black light, will glow yellow, green or blue. In contrast, healthy skin will have no reaction.

Cause

Non-segmental

In non-segmental vitiligo (NSV), there is usually some form of symmetry in the location of the patches of depigmentation. New patches also appear over time and can be generalized over large portions of the body or localized to a particular area. Vitiligo where little pigmented skin remains is referred to as vitiligo universalis. NSV can come about at any age (unlike segmental vitiligo, which is far more prevalent in teenage years).^[6]
Classes of non-segmental vitiligo include:

• Generalized Vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation^[8]
• Universal Vitiligo: depigmentation encompasses most of the body^[8]
• Focal Vitiligo: one or a few scattered macules in one area, most common in children^[8]
• Acrofacial Vitiligo: fingers and periorificial areas^[8]
• Mucosal Vitiligo: depigmentation of only the mucous membranes^[8]

Segmental

Segmental vitiligo (SV) differs in appearance, etiology and prevalence from associated illnesses. Its treatment is different from that of NSV. It tends to affect areas of skin that are associated with dorsal roots from the spine and is most often unilateral. It spreads much more rapidly than NSV and, without treatment, it is much more stable/ static in course and is not associated with auto-immune diseases. It is a very treatable condition that responds to topical treatment.^[6]

Differential diagnosis

Conditions with similar symptoms include the following:

• Pityriasis alba
• Tuberculoid leprosy
• Postinflammatory hypopigmentation
• Tinea versicolor^[8]
• Albinism
• Piebaldism^[8]
• Idiopathic guttate hypomelanosis^[8]
• Progressive macular hypomelanosis^[8]
• Primary adrenal insufficiency

Pathogenesis

Vitiligo is a disorder characterized by patchy loss of skin pigmentation. Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo. The immune system genes are associated with other autoimmune disorders.
In one case, the gene TYR, which makes the melanocyte more susceptible to the immune system in vitiligo, also makes the melanocyte more susceptible to the immune system in the skin cancer malignant melanoma. Therefore, people with vitiligo caused by the TYR gene are less likely to have malignant melanoma.
A genomewide association study found 10 independent susceptibility loci for generalized vitiligo, responsible for 7.4% of the genetic risk. Some patients had vitiligo alone; others had generalized vitiligo with other autoimmune diseases. Most loci were associated with both forms. (The exception was PTPN22, which was only associated with generalized vitiligo.) In the major histocompatibility complex (MHC) region, which controls the immune system, major association signals were identified in the class I gene region (between HLA-A and HLA-HGC9) and class II gene region (between HLA-DRB1 and HLA-DQA1). Outside the MHC region, association signals were identified near RERE, PTPN22, LPP, IL2RA, GZMB, UBASH3A and C1QTNF6 genes, which are associated with other autoimmune diseases. TYR encodes tyrosinase, which is not a component of the immune system, but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. The major alleles of TYR are associated with vitiligo, and the minor alleles are associated with malignant melanoma. Vitiligo-associated 402R tyrosinase may be more efficiently presented to the immune system. Melanoma-associated 402Q may fail to be identified by the immune system.^[9]
The transcriptional profile of melanocytes from vitiligo patients have been studied. Oligonucleotide microarrays containing approximately 16,000 unique genes were used to analyse mRNA expression in melanocytes from vitiligo patients and age-matched healthy controls. In total, 859 genes were identified as differentially expressed.^[10]
Vitiligo is sometimes associated with autoimmune and inflammatory diseases,^[11] commonly thyroid overexpression and underexpression. A study comparing 656 people with and without vitiligo in 114 families found several mutations (single-nucleotide polymorphisms) in the NALP1 gene. The NALP1 gene, which is on chromosome 17 located at 17p13, is on a cascade that regulates inflammation and cell death, including myeloid and lymphoid cells, which are white cells that are part of the immune response. NALP1 is expressed at high levels in T cells and Langerhan cells, white blood cells that are involved in skin autoimmunity. Polymorphisms of CD4 were shown to be associated with the vitiligo and other autoimmune diseases like type I Diabetes Mellitus.^[12]
Among the inflammatory products of NALP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β is expressed at high levels in patients with vitiligo. Some compounds inhibit caspase and interleukin-1β, and so might be useful drugs for vitiligo and associated autoimmune diseases. In one of the mutations, the amino acid leucine in the NALP1 protein was replaced by histidine (Leu155->His). The original protein and sequence is highly conserved in evolution, and found in humans, chimpanzee, rhesus monkey, and bush baby, which means that it is an important protein and an alteration is likely to be harmful. Addison's disease (typically an autoimmune destruction of the adrenal glands) may cause vitiligo.^[13][14]

Treatment

There are a number of treatments for vitiligo with the best evidence for applied steroids and the combination of ultraviolet light in combination with creams.^[15] Due to the higher risks of skin cancer, the NHS suggests phototherapy only be used if primary treatments are ineffective.^[16]

Phototherapy

Exposing the skin to UVB light from UVB lamps is the most common treatment for vitiligo. The treatments can be done at home with a domestic UVB lamp or in a clinic. It is important to control the exposure time so that the skin does not burn from overexposure. Treatment can take a few weeks if the spots are on the neck and face and if they existed not more than 3 years. If the spots are on the hands and legs and have been there more than 3 years, it can take a few months. In a clinic the treatments are done 2–3 times a week, and at home every day, which makes the home treatments more effective. Spots on a large area of the body may require full body treatment in a clinic or hospital. Both UVB broadband and UVB narrowband lamps can be used.^[17][18] There is no treatment that totally repigments the skin. Adding a psoralen, a photosensitizer, or an immunomodulant^[19] that increases the effect of the UV light can aid in partial repigmentation.
A 1997 report suggests that combining vitamin B₁₂ and folic acid supplements with sun exposure caused repigmentation in 52% of cases.^[20]
Ultraviolet light (UVA) treatments are normally carried out in a hospital clinic.Psoralen and ultraviolet A light (PUVA) treatment involves taking a drug that increases the skin's sensitivity to ultraviolet light, then exposing the skin to high doses of UVA light. Treatment is required twice a week for 6–12 months or longer. Because of the high doses of UVA and psoralen, PUVA may cause side effects such as sunburn-type reactions or skin freckling.^[16]
Narrowband ultraviolet B (UVB) phototherapy is now used more commonly than PUVA as it is less damaging to the skin. As with PUVA, treatment is carried out twice weekly in a clinic or every day at home, and there is no need to use psoralen.^[16]

Immune mediators

Tentative evidence supports a role for tacrolimus.^[21] There is tentative short term evidence for pimecrolimus but long term data is missing.^[22]

Skin camouflage

In mild cases, vitiligo patches can be hidden with makeup or other cosmetic camouflage solutions. If the affected person is pale-skinned, the patches can be made less visible by avoiding tanning of affected skin.^[8]

De-pigmenting

In cases of extensive vitiligo the option to de-pigment the unaffected skin with topical drugs like monobenzone, mequinol, or hydroquinone may be considered to render the skin an even colour. The removal of all the skin pigment with monobenzone is permanent and vigorous. Sun-safety must be adhered to for life to avoid severe sun burn and melanomas. Depigmentation takes about a year to complete.^[16]

Transplanting melanocytes

In October 1992, a scientific report was published of successfully transplanting melanocytes to vitiligo affected areas, effectively repigmenting the region.^[23] The procedure involved taking a thin layer of pigmented skin from the patient's gluteal region. Melanocytes were then separated out to a cellular suspension that was expanded in culture. The area to be treated was then denuded with a dermabrader and the melanocytes graft applied. Between 70 and 85 percent of patients experienced nearly complete repigmentation of their skin. The longevity of the repigmentation differed from person to person.^[24]

Notable cases

Michael Jackson said that he was diagnosed with vitiligo universalis.

• Michael Jackson announced publicly in a 90-minute interview with Oprah Winfrey in February 1993 that he had vitiligo. This was confirmed by the autopsy report following his death in 2009.^[25]
• Jon Hamm reported developing stress-induced vitiligo while working on the series Mad Men.^[26]
• UFC fighter Scott Jorgensen suffers from a particularly aggressive form of the disease and has received the unofficial nickname 'Spotty' as a result of the appearance it causes his skin to have. In 2012 Jorgensen claimed to have allowed the disease to "pretty much take over" and as a result give his skin a uniform colour.^[27]
• The Canadian model Chantelle Brown-Young has a prominent form of vitiligo. Her participation in the America's Next Top Model contest led to her being called a "vitiligo spokesmodel".^[28]
• US Rapper Krizz Kaliko also suffers from the condition and named his 2008 debut album vitiligo.