Aetiology

Vitiligo is caused by the T-cell-mediated destruction of melanocytes.

Intrinsic abnormalities present in melanocytes probably initiate inflammation through the activation of innate immunity. This inflammation leads to the recruitment of T cells, including cytotoxic T cells that are melanocyte-specific, recognising antigens produced specifically by melanocytes. These cytotoxic T cells destroy the melanocytes, leading to the loss of melanin production and pigmentation of the overlying keratinocytes.[14][15][16] This is manifest clinically as white macules and patches of the skin.

Pathophysiology

Characteristic abnormalities in melanocytes from patients with vitiligo include elevated reactive oxygen species and activation of the unfolded protein response, which generates the release of pro-inflammatory signals.[17][18][19][20][21] These cellular stress-induced signals most likely activate innate immune populations within the skin.[22]

Studies suggest that heat shock proteins, and other stress-induced cytokine signals released by melanocytes, activate nearby dendritic cells, enabling them to become more effective activators of T-cell responses.[23][24] Activated cytotoxic CD8 T cells then destroy melanocytes, leading to disease presentation.[25] 

T-cell activation and recruitment correlates with the expression of interferon gamma and interferon gamma-induced genes within the skin. Animal models suggest a role for both interferon gamma and the interferon gamma-induced chemokine CXCL10 in the progression and maintenance of depigmentation in vitiligo.[26] 

Genome-wide linkage and association studies have identified more than 50 vitiligo susceptibility loci.[12][27] Approximately 70% of genetic risk comes from common genetic variants and 30% from rare genetic variants.[12][27][28] Implicated genetic risk variants include members of the melanin biosynthesis pathway, immunoregulatory genes, and apoptotic and cytotoxic genes.[13] 

The majority of established treatments for vitiligo primarily act by suppressing immune responses directly within the skin, although they may also promote melanocyte growth and migration, particularly phototherapy through narrow-band UV-B. All of the above pathways are potential targets for the development of new treatments.[29]

Classification

Vitiligo European Task Force: revised classification/nomenclature of vitiligo[1]

Vitiligo has been classified clinically into two major forms: non-segmental vitiligo and the segmental variant.

Non-segmental vitiligo

  • Most common form of vitiligo. Characterised by asymptomatic, well-circumscribed, milky-white macules or patches involving various body parts, usually in a symmetrical pattern. May begin at any site of the body, but the face, genitals, fingers, and hands are frequently the initial sites. Subtypes include:

    • Acrofacial vitiligo: involved sites are usually limited to the face, head, hands, and feet. A distinctive feature is depigmentation of the distal fingers and around the facial orifices. It may later include other body sites, resulting in typical generalised vitiligo

    • Vitiligo universalis: the most extensive form of the disease, which generally occurs in adulthood. This term is generally used when depigmentation is virtually universal (>80% of the body surface), but some pigmentation may still be present. Hairs may also be spared

    • Mucosal vitiligo: typically refers to the involvement of the oral and/or genital mucosa. It may present as part of generalised vitiligo when associated with other sites of skin involvement, or as an isolated condition

    • Mixed vitiligo: refers to concomitant occurrence of segmental vitiligo with additional remote depigmentation on the contralateral side of the body

    • Focal vitiligo: refers to a small isolated patch that may evolve into more widely distributed vitiligo or the segmental variant.

Segmental vitiligo

  • Refers to the presence of one or more white depigmented macules or patches distributed on one side of the body, usually respecting the midline (although some lesions may partly cross the midline), early follicular involvement (leukotrichia), and rapid development over a few weeks or months, and an overall protracted course.

  • Rarely, segmental vitiligo may refer to multiple segmental lesions distributed either unilaterally or bilaterally. The onset may be simultaneous or not. A clear segmental distribution of the lesions with midline demarcation, together with the associated features described in monosegmental cases (i.e., leukotrichia, protracted course) distinguishes this diagnosis from vitiligo with bilateral distribution.

Fitzpatrick skin type[2]

Type I: always burns, never tans (pale white skin)

Type II: always burns easily, tans minimally (white skin)

Type III: burns moderately, tans uniformly (light brown skin)

Type IV: burns minimally, always tans well (moderate brown skin)

Type V: rarely burns, tans profusely (dark brown skin)

Type VI: never burns (deeply pigmented dark brown-to-black skin)

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