Vitiligo

Melanin is the pigment that gives skin its color; it is produced by skin cells called melanocytes.

Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo.[2] It is also thought to be caused by the immune system attacking and destroying the melanocytes of the skin.[15] A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo.[16]

The TYR gene encodes the protein 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.[2]

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.[2][17]

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.[18] 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 is found in humans, chimpanzee, rhesus monkey, and the bush baby. Addison's disease (typically an autoimmune destruction of the adrenal glands) may also be seen in individuals with vitiligo.[19][20]

Classification attempts to quantify vitiligo have been analyzed as being somewhat inconsistent,[23] while recent consensus have agreed to a system of segmental vitiligo (SV) and non-segmental vitiligo (NSV). NSV is the most common type of vitiligo.[2]

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. Extreme cases of vitiligo, to the extent that little pigmented skin remains, are referred to as vitiligo universalis. NSV can come about at any age (unlike segmental vitiligo, which is far more prevalent in teenage years).[11]

Classes of non-segmental vitiligo include the following:

• Generalized vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation[24]
• Universal vitiligo: depigmentation encompasses most of the body[24]
• Focal vitiligo: one or a few scattered macules in one area, most common in children[24]
• Acrofacial vitiligo: fingers and periorificial areas[24]
• Mucosal vitiligo: depigmentation of only the mucous membranes[24]

Segmental vitiligo (SV) differs in appearance, cause, and frequency of 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 spinal cord and is most often unilateral.[2][25] It is much more stable/static in course and its association with autoimmune diseases appears to be weaker than that of generalized vitiligo.[25] SV does not improve with topical therapies or UV light; however, surgical treatments such as cellular grafting can be effective.[11]

Chemical leukoderma is a similar condition due to multiple exposures to chemicals.[1] Vitiligo however is a risk factor.[1] Triggers may include inflammatory skin conditions, burns, intralesional steroid injections and abrasions.[1]

Other conditions with similar symptoms include the following:

• albinism
• halo nevus
• idiopathic guttate hypomelanosis (white sunspots)[24]
• piebaldism[24]
• pityriasis alba
• postinflammatory hypopigmentation
• primary adrenal insufficiency
• progressive macular hypomelanosis[24]
• tinea versicolor[24]
• tuberculoid leprosy.

Topical preparations of immune suppressing medications including glucocorticoids (such as 0.05% clobetasol or 0.10% betamethasone) and calcineurin inhibitors (such as tacrolimus or pimecrolimus) are considered to be first-line vitiligo treatments.[2]

In July 2022, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of vitiligo.[28]

Phototherapy is considered a second-line treatment for vitiligo.[2] Exposing the skin to light from UVB lamps is the most common treatment for vitiligo. The treatments can be done at home with an UVB lamp or in a clinic. The exposure time is managed so that the skin does not suffer 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 for more than 3 years, it can take a few months. Phototherapy sessions are done 2–3 times a week. Spots on a large area of the body may require full body treatment in a clinic or hospital. UVB broadband and narrowband lamps can be used,[29][30] but narrowband ultraviolet peaked around 311 nm is the choice. It has been constitutively reported that a combination of UVB phototherapy with other topical treatments improves re-pigmentation. However, some people with vitiligo may not see any changes to skin or re-pigmentation occurring. A serious potential side effect involves the risk of developing skin cancer, the same risk as an overexposure to natural sunlight.

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.[27]

Narrowband ultraviolet B (NBUVB) phototherapy lacks the side-effects caused by psoralens and is as effective as PUVA.[2] 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.[27] Longer treatment is often recommended, and at least 6 months may be required for effects to phototherapy.[31] NBUVB phototherapy appears better than PUVA therapy with the most effective response on the face and neck.[31]

With respect to improved repigmentation: topical calcineurin inhibitors plus phototherapy are better than phototherapy alone,[32] hydrocortisone plus laser light is better than laser light alone, ginkgo biloba is better than placebo, and oral mini-pulse of prednisolone (OMP) plus NB-UVB is better than OMP alone.[9]

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 unaffected skin.[24]

In cases of extensive vitiligo the option to depigment the unaffected skin with topical drugs like monobenzone, mequinol, or hydroquinone may be considered to render the skin an even color. The removal of all the skin pigment with monobenzone is permanent and vigorous. Sun-safety must be adhered to for life to avoid severe sunburn and melanomas. Depigmentation takes about a year to complete.[27]