Vitiligo

Vitiligo
Classification and external resources
Vitiligo of the hand in a dark-skinned individual.
ICD-10	L80.
ICD-9	709.01
OMIM	193200
DiseasesDB	13965
MedlinePlus	000831
eMedicine	derm/453
MeSH	D014820

Vitiligo (pronounced /ˌvɪtɨˈlaɪɡoʊ/) is a chronic disorder that causes depigmentation of patches of 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] The most common form is non-segmental vitiligo.

Signs and symptoms

Symptoms usually begin between ages 10 years and age 30 years,^[3] including:

• whitening or graying of hair^[4]
• loss of skin color inside the mouth^[3]
• loss of eye color^[4]

The most notable symptom of vitiligo is depigmentation of patches of skin that occurs on the extremities.^[5][3] Although patches are initially small, they often enlarge and change shape.^[1][3] When skin lesions occur, they are most prominent on the face, hands and wrists.^[5][3] Depigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus.^[5][3] Some lesions have hyperpigmentation around the edges.^[6] Patients who are stigmatised for their condition may experience depression and similar mood disorders.^[7]

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 generalised over large portions of the body or localised 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^[4]
• Universal Vitiligo: depigmentation encompasses most of the body^[4]
• Focal Vitiligo: one or a few scattered macules in one area, most common in children^[4]
• Acrofacial Vitiligo: fingers and periorificial areas^[4]
• Muscosal Vitiligo: depigmentation of only the mucous membranes^[4]

Segmental

Segmental vitiligo (SV) differs in appearance, aetiology 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. It spreads much more rapidly than NSV and, without treatment, it is much more stable/ static in course and not associated with auto-immune diseases and a very treatable condition that responds to topical treatment.^[6]

Vitiligo in a light-skinned individual

Vitiligo in a dark-skinned individual

A man affected by the vitiligo around the left eye.

Differential diagnosis

Conditions with similar symptoms include:

• Tinea versicolor^[4]
• piebaldism^[4]
• idiopathic guttate hypomelanosis^[4]
• progressive macular hypomelanosis^[4]

Pathogenesis

Vitiligo is a disorder characterized by patchy loss of skin pigmentation due to immune attacks on melanocytes, which can be caused by defects in many genes. 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. So 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 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.^[8]

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.^[9]

Vitiligo is sometime associated with autoimmune and inflammatory diseases,^[10] 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.

Among the inflammatory products of NALP1 are caspase 1 and caspase 5, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β is expressed at high levels in patients with vitiligo. There are compounds which 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.^[11][12]

Treatment

There is no cure for vitiligo, but there are a number of treatments that improve the condition. In fair-skinned people, avoiding tanning of normal skin can make patches of vitiligo much less noticeable. Treatment options generally fall into four groups:^[13]

Sunblock

A high protection sun-block (factor 20 or above) is applied to areas of vitiligo to prevent sunburn. Affected areas of skin are protected when the sun is strong, especially in the middle of the day by wearing, for example, a wide brimmed hat and long sleeved clothing.^[13]

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 sunlight and the sun tanning of unaffected skin.^[4]

Reversal

The traditional treatment used by dermatologists is the application of corticosteroid cream.^[14]

Studies have shown that immunomodulator creams such as Protopic and Elidel also cause repigmentation in some cases, when used with UVB narrowband treatments.^[15][16]

In October 1993, a scientific report was published of successfully transplanting melanocytes to vitiligo affected areas, effectively repigmenting the region.^[17] 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.^[18]

Ulltraviolet light (UVA) treatments are normally carried out in a hospital clinic. Psoralen and Ultraviolet A light (PUVA) treatment involves taking a drug which makes the skin very sensitive to light. The skin is then exposed to ultraviolet A light (UVA). Treatment is required twice a week for 6–12 months or longer. PUVA may cause side effects such as 'sunburn' type reactions or skin freckling.^[13] Narrowband ultraviolet B (UVB) phototherapy is now used more commonly than PUVA as it is less damaging to the skin than PUVA. As with PUVA, treatment is carried out twice weekly but there is no requirement to pre-sensitise the skin and the treatment sessions are much shorter.^[13]

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 to be adhered to for life to avoid severe sun burn and melanomas. Depigmentation takes about a year to complete.^[13]

Notable cases

Michael Jackson two years after he was diagnosed with vitiligo universalis, pictured in the early stages of the disease.^[19]

• Michael Jackson was diagnosed with vitiligo in 1986. In a 90-minute interview with Oprah Winfrey in February 1993, Jackson claimed that he didn't bleach his skin, stating for the first time that he had vitiligo. A friend claimed he started wearing his signature sequin glove to cover the vitiligo that had begun to appear in the early 80s.^[20] It is also confirmed on his autopsy report.^[21][22] It was also confirmed by Jackson during a leaked deposition tape in 1996, that he did not "bleach" his skin^[23]. The tape was leaked months after his death in June of 2009. According to police reports, 19 tubes of hydroquinone and 18 tubes of benoquin(monobenzone) were found in Michael Jackson's home after his death.^[24] In July 2010, Michael Jackson's eldest son Prince Michael Jr is seen in a picture with a patch of de-pigmented skin on his right underarm leading to speculations that he may be affected by vitiligo like his father Michael Jackson.^[25]
• Graham Norton the Irish television personality.^[26]
• Lee Thomas, a news anchor and entertainment reporter for WJBK (Fox) Detroit.^[27][28][29]
• Yvette Fielding, British TV presenter, has had vitiligo from age 11; her mother developed it at age 24.^[30][31]
• John Wiley Price, the Dallas County Commissioner, also has vitiligo.^[32]
• Amitabh Bachchan, the famous bollywood actor , also has vitiligo.^[33]
• Scott Jorgensen, the WEC fighter, also has vitiligo. ^[34]
• Krizz Kaliko, rapper has vitiligo and even used the condition as the title of his first album.
• Jon Hamm, Mad Men actor also has vitiligo. ^[35]

See also

• Alphos
• Albinism
• Leucism
• Melanism
• Pityriasis alba
• Quadrichrome vitiligo
• Selective ultraviolet phototherapy
• List of cutaneous conditions
• Nevus depigmentosus

Notes

References

• Millington GW, Levell NJ (September 2007). "Vitiligo: the historical curse of depigmentation". International Journal of Dermatology 46 (9): 990–5. doi:10.1111/j.1365-4632.2007.03195.x. PMID 17822509. 

External links

• Overview at Davidson College
• DermAtlas 45

Support organizations

• Vitiligo Support International
• National Vitiligo Sciety US
• Vitiligo Society UK
• Swedish Vitiligo Association
• The Turning White Foundation