Vitiligo

Vitiligo is a chronic autoimmune condition characterised by the loss of skin pigment, resulting in pale or depigmented patches that may appear on any part of the body. Although its precise cause is unknown, research indicates contributions from immune dysregulation, genetic susceptibility, oxidative stress, environmental triggers, and localised skin injury. The condition often progresses slowly, with patches remaining in relatively stable areas but varying slightly in pigmentation over time. Treatment options include topical medications, phototherapy, surgical techniques and cosmetic approaches, although no definitive cure exists.

Signs and Symptoms

The primary manifestation of vitiligo is the appearance of well-defined pale or white macules resulting from the destruction or dysfunction of melanocytes. These patches commonly develop on the hands, feet, face, wrists, and areas surrounding body orifices, including the eyes, mouth, nostrils, navel and genital region. Some individuals experience mild itching prior to the formation of new lesions. Patches often expand and change shape, and some display a ring of hyperpigmentation at the margins.
Vitiligo can lead to significant psychosocial effects. Individuals who feel stigmatised may develop depression, anxiety or related mood disturbances.

Causes

Although many hypotheses have been proposed, evidence strongly implicates the immune system in the destruction of melanocytes. Vitiligo is considered a multifactorial disorder, with both genetic predisposition and environmental factors contributing to its onset.
Environmental triggers may disrupt redox balance within melanocytes, inducing the unfolded protein response and releasing inflammatory cytokines that activate immune pathways. Sunburn, emotional stress, chemical exposures and mechanical injury can precipitate or worsen lesions. The tendency for new patches to arise at sites of friction or trauma illustrates the Koebner phenomenon.

Immune Mechanisms

Melanin, produced by melanocytes, determines skin pigmentation. Variants in genes regulating immune activity or melanocyte function have been linked to vitiligo. Genome-wide association studies have identified more than thirty susceptibility loci, including the TYR gene, which encodes tyrosinase, a key melanogenic enzyme and a major autoantigen. Vitiligo involves autoimmune targeting of melanocytes, facilitated by innate and adaptive immune responses.

Autoimmune Associations

Vitiligo frequently co-occurs with other autoimmune conditions, such as Hashimoto’s thyroiditis, type 1 diabetes, scleroderma, rheumatoid arthritis, psoriasis, alopecia areata, Addison’s disease, pernicious anaemia, coeliac disease and systemic lupus erythematosus. Mutations in NLRP1, a component of innate immunity, can elevate levels of interleukin-1β and interleukin-18, contributing to inflammatory pathways implicated in vitiligo.

Oxidative Stress

Genetic studies have shown an association between vitiligo and alterations in genes regulating antioxidant defence, including CAT, SOD1–3, NFE2L2, HMOX1, GSTM1 and GSTT1. Elevated reactive oxygen species may damage melanocytes and initiate autoimmune responses.
Mitochondrial dysfunction in melanocytes can lead to the release of mitochondrial DNA into surrounding tissues, activating the cGAS–STING pathway and promoting inflammatory cytokine production. This can recruit cytotoxic CD8⁺ T cells, enhancing melanocyte destruction. Mitochondrial antioxidants, NRF2 inhibitors and TBK1 inhibitors are being explored as emerging therapeutic approaches.

Diagnosis

Diagnosis is clinical, supported when necessary by Wood’s lamp examination, in which affected skin fluoresces and becomes more clearly contrasted against normal tissue. The tool is useful for early detection and monitoring treatment response. Differential diagnosis includes chemical leukoderma, white sunspots and pigmentary disorders following burns, irritation or steroid injections.

Classification

Vitiligo classification has historically varied, but contemporary consensus distinguishes two principal forms: nonsegmental vitiligo (NSV) and segmental vitiligo (SV).

Nonsegmental Vitiligo

NSV is the most common form and typically displays bilateral symmetry. New patches may appear over time and spread widely or remain localised. Subtypes include:

• Generalised vitiligo: widespread, randomly distributed patches.
• Universal vitiligo: near-total loss of pigment.
• Focal vitiligo: isolated patches, often seen in children.
• Acrofacial vitiligo: affecting digits and periorificial regions.
• Mucosal vitiligo: limited to mucous membranes.

NSV can arise at any age.

Segmental Vitiligo

SV is usually unilateral and follows dermatomal patterns associated with dorsal roots of the spinal cord. It tends to stabilise more quickly, has weaker associations with autoimmune diseases and responds poorly to topical or light-based therapies, although surgical grafting techniques may be effective.

Treatment

Vitiligo cannot be cured, but several interventions can reduce the appearance of lesions or stimulate repigmentation.

Immune-Modulating Therapies

Topical corticosteroids—such as clobetasol (0.05%) and betamethasone (0.1%)—and calcineurin inhibitors, including tacrolimus and pimecrolimus, are considered first-line treatments. In 2022, ruxolitinib cream was approved in the United States for vitiligo, targeting Janus kinase-mediated inflammatory pathways.

Phototherapy

Ultraviolet B (UVB) light therapy is a second-line treatment. Narrowband UVB is preferred due to improved safety and efficacy. Combination therapy with topical agents can enhance repigmentation. Limitations include increased skin cancer risk, prompting cautious use in some healthcare systems.

Surgical and Cosmetic Approaches

Where medical therapies are ineffective—particularly in stable segmental vitiligo—procedures such as cellular grafting or melanocyte transplantation may restore pigmentation. Cosmetic camouflage techniques, including medical-grade makeup and self-tanners, can reduce the visibility of lesions.
Lesions on the face respond most readily due to thinner skin, while those on the hands, feet and joints are the most resistant to repigmentation.