Vitiligo or skin depigmentation: understanding this skin condition in depth.

The mechanism behind vitiligo corresponds to the loss of melanocytes, epithelial cells located at the dermo-epidermal junction whose main function is the synthesis of melanin, responsible for skin pigmentation and its protection against UV rays. These pigments are then transferred, through the dendritic extension of melanocytes, into keratinocytes which play a role in the inflammatory response. There are two main mechanisms that explain the loss of melanocytes during vitiligo: The disappearance of melanocytes mediated by CD8+ cytotoxic T lymphocytes and their cellular death by apoptosis.

In a predisposed patient, abnormalities in melanocytes lead to the release of danger signal molecules (DAMPs) and inflammatory cytokines, initially activating innate immunity (immediate response), followed by adaptive immunity (lymphocytes and antibodies). Lymphocytes (LTEM and LTRM), expressing CXCR3 and/or CCR6 receptors, primarily produce cytokines TNF-α and IFN-γ, which are responsible for the destruction of melanocytes and the characteristic depigmentation of vitiligo.

Vitiligo is thus caused by the disappearance or destruction of melanocytes in various parts of the body.

This deficiency is primarily due to a genetic predisposition. The statistics on this disease have reported that 20% of people affected by vitiligo have at least one first-degree relative with this disease and are 7 to 10 times more likely to be affected by vitiligo if they have a first-degree relative with this disease. Other causes can trigger or worsen this phenomenon in predisposed individuals such as:

• Environmental factors : Exposure to dust mites, induced by the protease they produce, could lead to the destruction of E-cadherins, cellular adhesion proteins responsible for tissue coherence. They play a key role in the adhesion of melanocytes to the keratinocytes of the epidermis. Their dysfunction could be involved in the deterioration and disappearance of melanocytes, thus contributing to the depigmentation observed in vitiligo. Contact with certain chemicals causes oxidative stress in melanocytes, which disrupts the endoplasmic reticulum (ER) and leads to the accumulation of misfolded proteins. This activates an inflammatory response and contributes to the destruction of melanocytes.

• The Koebner Phenomenon: It is involved in the spread of vitiligo patches due to friction and micro-traumas, which triggers an inflammatory response and activates T lymphocytes.

• Stress : indeed, psychological or physiological stress could be a factor promoting the onset or worsening of the disease. Some studies have shown a link, but this hypothesis has not been confirmed as such.

Vitiligo can present in two forms, depending on the origin of the depigmentation:

• Segmental or Unilateral Vitiligo: It is the least common, at 10%, and is characterized by depigmented patches on one side of the body within defined areas. The lesions are asymmetrical, with rapid progression in the initial months but stabilizing thereafter. It is sometimes associated with hair depigmentation. Some scientists hypothesize that localized damage is due to overactive nerves in a dermatome, releasing pro-inflammatory neuropeptides and free radicals, causing targeted destruction of melanocytes in the area.

• Non-segmental or generalized vitiligo: This is the most common form, with symmetrical lesions on both sides and all over the body. The most frequently affected areas are those subjected to friction or microtraumas. The progression of the disease can either worsen or stabilize. The bilateral distribution of non-segmental vitiligo is linked to its systemic nature, where the immune system attacks the melanocytes in a more diffuse manner throughout the body. Universal vitiligo is a rarer form of vitiligo, where the majority of the skin surface is depigmented and its onset is often progressive.

Although vitiligo is a benign condition, its aesthetic appearance can have psychological implications. That's why various treatments have been developed to reduce its appearance and limit its progression.

• Oral and topical corticosteroids work by blocking the immune response, inhibiting the production of pro-inflammatory cytokines. This can slow the progression of vitiligo and promote repigmentation.

• Calcineurin inhibitors are used to treat vitiligo by limiting inflammation. By blocking calcineurin, a protein involved in the activation of T lymphocytes, they reduce the production of pro-inflammatory cytokines. Simultaneously, they stimulate the synthesis of anti-inflammatory cytokines, such as certain interleukins, thus helping to regulate the immune response.

• The Janus kinase inhibitor, an enzyme that plays a key role in the inflammatory signaling pathways involved in the depigmentation of vitiligo. JAK proteins transmit signals from cytokine receptors located on the cell surface to the nucleus, thus influencing the immune response.

• Phototherapy is a standard treatment for vitiligo, particularly recommended for extensive and resistant forms. PUVA therapy combines a photosensitizer, psoralen, with exposure to UVA (320-400 nm) to penetrate deeply into the skin. Once activated, psoralen forms bonds with the DNA of T lymphocytes, limiting their inflammatory action. Narrowband UVB therapy (311 nm), on the other hand, reduces the autoimmune attack against melanocytes and stimulates melanogenesis. It thus promotes their proliferation and the production of melanin, contributing to the repigmentation of the skin.

• The excimer laser emits high-intensity UVB light at 311 nm, directly targeting the mechanisms responsible for depigmentation. Its action is based on the suppression of inflammation and the elimination of T lymphocytes through apoptosis, thus limiting the immune attack against melanocytes.

• Surgical treatments such as melanocyte grafting are only recommended for segmental vitiligo, a localized form with no risk of spreading. These techniques involve transplanting small skin fragments containing active melanocytes taken from a healthy area of the patient.