Vitiligo
Vitiligo is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure, and susceptibility to it may be affected by regional environmental risk factors, especially early in life. Treatment options include topical medications, light therapy, surgery and cosmetics. The condition causes patches of a light peachy color of any size, which can appear on any place on the body; in particular, nonsegmental vitiligo, the common form, tends to progress, affecting more of the skin over time. Vitiligo spots on the skin can also vary in pigmentation over long periods, although they will stay in relatively the same areas.
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. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders.Causes
Although multiple hypotheses have been suggested as potential triggers that cause vitiligo, studies strongly imply that changes in the immune system are responsible for the condition. Vitiligo has been proposed to be a multifactorial disease with genetic susceptibility and environmental factors both thought to play a role. It is 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, thus mounting an immune response.The National Institutes of Health states that sometimes an event, like a sunburn, emotional distress, or exposure to a chemical, can trigger or exacerbate the condition. Skin depigmentation in particular areas in vitiligo can also be triggered by mechanical trauma: this is 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.
Immune
Variations in genes that are expressed in the immune cells or in the melanocytes have both been associated with vitiligo. It is thought to be caused by the immune system attacking and destroying the melanocytes of the skin. A genome-wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. One of them is the TYR gene that encodes the protein tyrosinase, which is an enzyme of the melanocytes that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo.Autoimmune associations
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. The original protein and sequence are highly conserved in evolution, and are found in humans, chimpanzees, rhesus monkeys, and bush babies. Addison's disease may also be seen in individuals with vitiligo.
Oxidative stress
Numerous whole-exome sequencing studies have demonstrated that vitiligo is associated with polymorphisms in genes involved in the response to oxidative stress, such as CAT, SOD1, SOD2, SOD3, NFE2L2, HMOX1, GST-M1, or GST-T1, supporting the association of elevated levels of reactive oxygen species in melanocytes with the induction of an autoimmune response.Thus, diseases presenting with altered mitochondrial function such as MELAS, Vogt-Koyanagi-Harada syndrome and Kabuki syndrome are associated with increased risk of vitiligo.
In line with these observations, genetic alterations in mitochondrial DNA of melanocytes associated with altered mitochondrial function lead to a release of mtDNA that can be detected in the skin of vitiligo patients. This mtDNA can be sensed by the cGAS-STING pathway, resulting in pro-inflammatory cytokine and chemokine production promoting the recruitment of cytotoxic CD8+ T cells. Mitochondrial antioxidants, NRF2 inhibitors, and TBK1 inhibitors are emerging as potential therapeutic options to block this cascade of events.
Diagnosis
An ultraviolet light can be used in the early phase of this disease for identification and to determine the effectiveness of treatment. Using a Wood's light, skin will change colour when it is affected by certain bacteria, fungi, and changes to pigmentation of the skin.Classification
Classification attempts to quantify vitiligo have been analyzed as being somewhat inconsistent, while recent consensus has agreed to a system of segmental vitiligo and non-segmental vitiligo. NSV is the most common type of vitiligo.Non-segmental
In non-segmental vitiligo, 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 occur at any age.Classes of non-segmental vitiligo include the following:
- Generalized vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation
- Universal vitiligo: depigmentation encompasses most of the body
- Focal vitiligo: one or a few scattered macules in one area, most common in children
- Acrofacial vitiligo: fingers and periorificial areas
- Mucosal vitiligo: depigmentation of only the mucous membranes
Segmental
Differential diagnosis
Chemical leukoderma is a similar condition due to multiple exposures to chemicals. Vitiligo, however, is a risk factor. Triggers may include inflammatory skin conditions, burns, intralesional steroid injections, and abrasions.Other conditions with similar symptoms include the following:
- albinism
- halo nevus
- idiopathic guttate hypomelanosis
- piebaldism
- pityriasis alba
- postinflammatory hypopigmentation
- primary adrenal insufficiency
- progressive macular hypomelanosis
- tinea versicolor
- tuberculoid leprosy
Treatment
Immune mediators
Topical preparations of immunosuppressing medications, including glucocorticoids and calcineurin inhibitors are considered to be first-line vitiligo treatments.In July 2022, ruxolitinib cream was approved for medical use in the United States for the treatment of vitiligo.
Phototherapy
Phototherapy is considered a second-line treatment for vitiligo. Exposing the skin to light from UVB lamps is the most common treatment for vitiligo. The treatments can be done at home with a 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 have existed for 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, but narrowband ultraviolet peaked around 311 nm is the choice. It has been consistently 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 their skin or re-pigmentation occurring. A serious potential side effect involves the risk of developing skin cancer, the same risk as overexposure to natural sunlight.Ultraviolet light treatments are normally carried out in a hospital clinic. Psoralen and ultraviolet A light treatment involves taking a drug that increases the skin's sensitivity to ultraviolet light and then exposing the skin to high doses of UVA light. Treatment is required twice a week for 6–12 months or longer. Due to the high doses of UVA and psoralen, PUVA may cause side effects such as sunburn-type reactions or skin freckling.
Narrowband ultraviolet B phototherapy lacks the side effects caused by psoralens and is as effective as PUVA. 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. Longer treatment is often recommended, and at least 6 months may be required for effects to phototherapy. NBUVB phototherapy appears better than PUVA therapy, with the most effective response on the face and neck.
Concerning improved repigmentation: topical calcineurin inhibitors plus phototherapy are better than phototherapy alone, hydrocortisone plus laser light is better than laser light alone, ginkgo biloba is better than placebo, and oral mini-pulse of prednisolone plus NB-UVB is better than OMP alone.