Vitiligo

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. The incidence worldwide is less than 1%. The most common form is non-segmental vitiligo.

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

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.

Classes of non-segmental Vitiligo include:

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. 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.

Conditions with similar symptoms include:

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.

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.

Vitiligo is sometime associated with autoimmune and inflammatory diseases, 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.

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:

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.

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 sun tanning of unaffected skin.

The traditional treatment used by dermatologists is the application of corticosteroid cream.

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

With one patient, repigmentation occurred significantly when another autoimmune disease, celiac disease, was treated. Eliminating gluten from the diet, a celiac patient who had Vitiligo reported repigmentation starting within 6 months of treatment. With the elimination of gluten, repigmentation continued to increase for 3–5 years, though not totally. This occurred with a patient who had Vitiligo for 25 years prior to learning of their diagnosis and treatment for Celiac Disease.

A 1997 report suggests that combining Vitamin B12 and folic acid supplements with sun exposure caused repigmentation in 52% of cases.

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

Ultraviolet 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. 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 but there is no requirement to pre-sensitise the skin and the treatment sessions are much shorter.

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.

Vitiligo Treatment