Vitiligo and disorders of pigmentation

• Vitiligo is an acquired autoimmune disorder in which the immune system destroys functional melanocytes, leaving well-demarcated, chalky-white patches of skin (and sometimes hair).
• Non-segmental vitiligo, with symmetric patches on both sides of the body, is the common form (80 to 90% of cases); segmental vitiligo is unilateral, earlier in onset, and less often autoimmune.
• It affects roughly 0.5 to 2% of people worldwide, often starts before the age of 20 years, and can carry a major psychosocial burden at any age or extent.
• Diagnosis is clinical; a Wood's lamp makes the patches (and subtle, spreading confetti lesions) stand out, and thyroid dysfunction is the most common associated autoimmune problem, so thyroid function should be checked.
• Management follows national guidelines: photoprotection, off-label potent topical corticosteroids once daily or topical calcineurin inhibitors twice daily, plus narrowband UVB when needed, and the topical Janus kinase (JAK) inhibitor ruxolitinib cream for eligible patients with non-segmental vitiligo aged 12 years or older.

By the end of this page you should be able to:

1. Define vitiligo, explain melanocyte loss, and classify it as non-segmental, segmental, mixed or unclassified.
2. Recognise the typical history and examination findings, use a Wood's lamp, and separate vitiligo from its mimics.
3. Plan the assessment for an autoimmune comorbidity, including thyroid disease, using the investigations in the table.
4. Choose and dose topical therapy, phototherapy and systemic treatment following current guidelines (BAD vitiligo guideline 2021, AAD, NICE CKS, StatPearls).
5. Counsel a patient about ruxolitinib cream, camouflage, depigmentation, surgery and maintenance.
6. Describe albinism and melasma and how they differ from vitiligo.

The defining problem is the melanocyte, the cell that produces melanin, the pigment that colours skin and protects it from ultraviolet light. In vitiligo these cells stop working and are destroyed, so a patch of skin contains no pigment rather than just less of it. The condition is usually lifelong and, although it is not dangerous in itself, it can change markedly over time, with periods of spread and periods of stability. Spontaneous partial repigmentation can occur, and repigmentation that does occur often starts around hair follicles, giving a speckled appearance. ^[3][6]

Classification by distribution is the standard way to describe the disease ^[5][9]:

• Non-segmental vitiligo (NSV) accounts for 80 to 90% of cases. It tends to be symmetric, may appear in acrofacial, generalised, universal, focal, mucosal or follicular forms, and is the form linked to other autoimmune diseases. Universal vitiligo means complete or nearly complete loss of pigment over more than 80% of the body surface and usually follows generalised disease.
• Segmental vitiligo is usually unilateral, often follows a dermatome (the trigeminal nerve distribution is the commonest), has an earlier age of onset, spreads rapidly at first, then tends to stabilise; it affects 20 to 30% of children and about 5% of adults with vitiligo, and is less often associated with autoimmunity.
• Mixed vitiligo is segmental and non-segmental disease in the same patient.
• Unclassified (or focal) lesions are small, isolated patches that have not evolved over at least 2 years.

The vitiligo global issues consensus conference revised this nomenclature; in everyday practice, the first question is simply “segmental or not?”, because the answer changes the expected course and the comorbidity screen. ^[9]

Vitiligo is the most common depigmenting skin disorder. Worldwide prevalence is 0.5 to 2% of the population, with reported rates varying by geography, skin phototype and social or cultural stigma (patches are more visible on darker skin) ^[3][5][9]. The BAD referral guideline quotes an incidence of 1% of the world population, with 50% of cases appearing before the age of 20 years, and a family history in up to 30% of patients ^[3]. The BAD patient leaflet states vitiligo affects about 1 in 100 people worldwide, usually starts before the age of 20 years but can begin at any age, and occurs in all skin tones. ^[2]

Age patterns are well established: childhood onset is common (affecting roughly 30% of people with vitiligo), onset is uncommon before the age of 2 years (89% of cases occur after the age of 4 years), almost 50% of people present before the age of 20 years, and nearly 70 to 80% before the age of 30 years. ^[5] A genetic review found no significant global sex difference in prevalence overall (0.5 to 2%), but higher reported rates in darker-skinned populations (African 1 to 2.5%, some Indian groups up to 3 to 4%) and a female predominance in most clinic series. ^[9]

Risk factors and associations ^[2][3][9]:

• Family history is present in 20 to 30% of patients in most series, with risk rising sharply with closer kinship: about 5 to 7% if one parent is affected, 6 to 8% for a sibling, and 30 to 40% if both parents are affected. Heritability is estimated at 75 to 80%.
• Monozygotic twin concordance is 23 to 26%, against 4 to 6% in dizygotic twins, which strongly supports a genetic component but also shows that genes alone do not cause disease.
• Autoimmune comorbidity is the association that matters most in practice (see “Associated autoimmune disease”).
• Triggers include skin trauma (the Koebner phenomenon, in which new patches form at sites of cuts, burns, friction or pressure), psychological stress, and exposure to certain phenolic chemicals; sunburn can also precipitate new lesions.

Vitiligo is best understood as an autoimmune condition in which melanocytes are destroyed, probably through several converging mechanisms ^[2][4][6][9]:

1. Loss of immune tolerance. Genes of the MHC region (in particular HLA-A2 and HLA-DQ) and other immune genes (PTPN22, CTLA4, NLRP1, FOXP3) are involved in antigen presentation and T-cell regulation. Reduced regulatory T-cell function lets melanocyte-specific (for example MELAN-A-specific) CD8-positive cytotoxic T cells escape and attack melanocytes.
2. Interferon gamma and chemokines. Interferon gamma released in the skin activates the JAK-STAT signalling pathway, which induces chemokines such as CXCL10; these recruit further cytotoxic T cells, creating a self-sustaining inflammatory loop. This is why JAK inhibitors can reverse the process.
3. Oxidative stress. Melanocytes in vitiligo are unusually sensitive to reactive oxygen species, and antioxidant defences such as catalase are reduced. Oxidative stress can damage melanocyte DNA and proteins, and may be the initial trigger that exposes melanocyte antigens to the immune system.
4. Melanocyte-intrinsic vulnerability. Some genetic variants affect melanin synthesis enzymes such as tyrosinase (TYR) and MC1R, making melanocytes more fragile and immunogenic.
5. Environmental triggers. Ultraviolet light, phenolic chemicals, mechanical trauma (Koebner phenomenon) and possibly stress or viral infection can initiate or flare disease in a genetically susceptible person.

The endpoint is the same in every pathway: autoimmune destruction of melanocytes, so that an area of skin loses all of its pigment. Because the hair follicle retains a reservoir of melanocyte stem cells, patches that contain pigmented hairs can repigment; glabrous (hairless) areas (fingertips, lips) are harder to treat. ^[1][4]

Vitiligo belongs to a family of autoimmune conditions, and patients (and their first-degree relatives) have an increased risk of others. Thyroid disease is the commonest, occurring in 20% of patients over the age of 20 years, and both vitiligo and autoimmune thyroid disease share HLA-linked susceptibility. Other associations include type 1 diabetes mellitus, pernicious anaemia, alopecia areata, Addison's disease, systemic lupus erythematosus, rheumatoid arthritis and psoriasis. ^[2][3][9]

Because of this, assessment of new vitiligo should include a history of thyroid or other autoimmune symptoms and, where relevant, blood tests (see the investigations table). ^[5]

History. Patients describe flat, chalky-white patches that appear over days to weeks and then either stay put or enlarge. The patches are not scaly, not itchy and not painful; itching may precede a new patch. Sites of mechanical trauma (waistband, scratch lines) may be affected (Koebner phenomenon). Hair within patches may turn white (leukotrichia). Patches are often symmetric initially on the hands, forearms, feet and face (periocular and perioral), with later spread to the axillae, groin and genitalia. ^[6][5]

Examination. Lesions are well-demarcated macules and patches that are truly depigmented (milky or porcelain white), not merely hypopigmented. They are flat and non-scaly. Borders are usually convex and may show a “trichrome” pattern (depigmented centre, pale zone, normal skin). Confetti lesions, trichrome borders, inflammatory erythema with scale at the edge, or new patches after trauma indicate active, spreading disease. The disease is graded by body surface area involved and by whether it is active or stable. ^[5][6]

Wood's lamp. In a darkened room the depigmented patches fluoresce a bright blue-white and are much easier to see, especially on fair skin and at the margins of spreading lesions; the lamp also helps to define the full extent for treatment planning. It does not diagnose vitiligo on its own, but it is the single most useful bedside tool. ^[4][2][8]

Psychosocial impact. Depression, anxiety and impaired self-esteem are common and are worse with visible or extensive disease, darker skin and in adolescents; they should be assessed routinely, not treated as an afterthought. ^[5]

Figure 1Vitiligo2

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Long description

Vitiligo of the hand in a person with dark skin.

Diagnosis is clinical. Blood tests do not diagnose vitiligo but help identify associated autoimmune disease and treatment needs.

Referral to dermatology is appropriate when the diagnosis is uncertain, the disease is progressing rapidly, the patient has segmental vitiligo, more than 10% of the body surface area is involved, there is significant psychosocial impact, or there is no response or intolerance to topical treatment. ^[5]

The main practical distinction is between true depigmentation (vitiligo, which is chalk-white and fluorescent under Wood's lamp) and hypopigmentation (lighter than normal skin but not white). A second distinction is history: vitiligo is acquired, whereas the congenital pigmentary disorders are present from birth. The full list of mimics is long (post-inflammatory, infective, chemical, neoplastic) and the table summarises the bedside clues; where doubt remains, a biopsy and dermatology referral resolve it. ^[5][6]

Management should follow the current named guidelines: the BAD guidelines for the management of people with vitiligo 2021 (published online 23 June 2021; literature appraised up to May 2019; revision due 2026), the AAD public guidance on diagnosis and treatment, the NICE CKS (management based on BAD and International Vitiligo Task Force recommendations) and StatPearls. The 2021 BAD guideline is chiefly an adult guideline, and many vitiligo treatments are used off-label. ^[1][4][5][6]

Principles of treatment. There is no cure. Treatment aims to stop spread in active disease, repigment (often partially and slowly) and protect the depigmented skin from sunburn, while supporting the patient psychologically. Treatment cannot guarantee repigmentation; about 40% of patients lose some colour within a year of stopping successful treatment, so maintenance and expectations matter. ^[2][4]

Non-pharmacological measures (all patients) ^[2][5][4]:

• Photoprotection. Vitiligo patches burn easily. Advise high-factor (SPF 50 or more) sunscreen with a 4 or 5 star UVA rating on the patches and surrounding skin before going outdoors, reapplying every 2 hours (15 to 30 minutes before exposure in the BAD leaflet). Add clothing, hats and UV-protective sunglasses; avoid sunbeds. Sunscreens supplement, but do not replace, shade and clothing.
• Vitamin D. Patients who avoid all sun exposure may become deficient; measure vitamin D levels and, if reduced, advise supplementation (10 to 25 micrograms per day) plus dietary sources.
• Skin camouflage (camouflage makeup, self-tanner, skin dyes) gives immediate cosmetic benefit while medical treatment takes effect: self-tanning products cover for 3 to 5 days and camouflage makeup is applied daily. Changing Faces and the Vitiligo Society offer counselling and practical help.

Topical corticosteroids (first line, NICE CKS/BAD) are the most useful single treatment for limited non-segmental vitiligo: a potent or very potent preparation applied once daily, off-label, avoiding the periocular area, reviewed every 3 to 6 months for response and adverse effects. ^[5][2] Topical calcineurin inhibitors (tacrolimus 0.03 and 0.1% ointment, pimecrolimus cream) are the usual alternative for face and flexures because they do not cause skin thinning, and are applied twice daily; they are not offered in pregnancy. ^[2][4][5] An intermittent regimen (for example, one week of potent steroid alternating with one week or more of calcineurin inhibitor) is suggested for thin-skinned areas. ^[5]

Oral corticosteroids can slow rapidly progressive disease (systemic, tapered), but are not used for long-term control. ^[4][2]

Ruxolitinib cream is the first medication approved specifically to restore colour in non-segmental vitiligo: approved for patients aged 12 years or older, applied as a thin layer twice daily to a limited area. In the two phase 3 trials about 30% of patients achieved 75% repigmentation at week 24, and about 15% achieved 90% repigmentation at week 24; treatment should be reassessed if there is no sign of repigmentation after 24 weeks. The most common side effects are acne and itch at the application site. It has been approved by NICE for NHS use. ^[4][2] Because JAK inhibitors block the interferon gamma-driven inflammatory loop central to vitiligo, the mechanism matches the disease rather than just masking it. ^[1][9]

Phototherapy. Narrowband UVB is the standard light treatment: 2 to 3 sessions per week in the department, for a minimum of 12 weeks and generally 12 months or longer. It is used for more extensive or active disease and is often combined with topical therapy; repigmentation is gradual. NB-UVB is also used for children. Complete repigmentation is uncommon and usually gradual, even with prolonged courses; in a pooled analysis, about 36% of patients achieved marked (at least 75%) repigmentation after 12 months of NB-UVB, with the face and neck responding best and the hands and feet least. Excimer laser can be used for small, stable patches. Home phototherapy may be available in some centres. ^[2][4][6]

Surgical treatment is considered when stable patches have not responded to medical therapy. Two approaches are skin grafting and non-cultured melanocyte/keratinocyte transplantation (cell transplant). Most repigmentation after cell transplant occurs within 6 months, with continued improvement up to 12 months. Surgery is usually not offered if the vitiligo has been active in the previous 12 months (new or enlarging spots), and is avoided where the patient tends to form raised scars. ^[4]

Depigmentation (rarely used). If vitiligo covers most of the body, or large areas of the face and hands, and the patient does not want further repigmentation treatment, the remaining normal pigment can be removed to even skin tone. This is permanent and takes 1 to 4 years. It is a specialist decision. ^[4]

Maintenance. To prevent fading, dermatologists often prescribe a topical preparation a few times a week after successful repigmentation, together with continued sun protection and self-care. ^[4]

Psychological support is part of management, not an optional extra: refer for CBT, self-help resources, or specialist psychological services when distress is moderate to severe. ^[5][4]

• Psychosocial impact. A meta-analysis (NICE CKS) reports anxiety in people with vitiligo with an odds ratio of 6.14 (95% CI 3.35 to 11.24) compared with healthy controls; pooled prevalence of clinical anxiety disorder 12% (95% CI 7 to 16%) and anxiety symptoms 34% (95% CI 21 to 46%), with female patients affected more (OR 2.24, 95% CI 1.31 to 3.84). Depression, poor body image and isolation are common. ^[5]
• Sunburn of depigmented skin lacking protective melanin.
• Treatment effects can become complications: skin atrophy and striae from prolonged potent steroids, burns or post-inflammatory pigment change from phototherapy or procedures.
• Social and practical burden (education, employment, relationships), which makes vitiligo genuinely a medical condition rather than a cosmetic one. ^[4]

Vitiligo is chronic and unpredictable. For most people, spontaneous repigmentation is unlikely and new patches can appear years later, even after successful treatment. Prognostic factors include type (segmental disease usually stabilises; non-segmental disease is more relapsing), activity (active disease spreads, sometimes rapidly), site (face repigments best; fingertips, toes and lips most resistant), extent and age of onset. Repigmentation depends heavily on surviving hair follicles in the patch. ^[2][4][5]

There is no known way to prevent vitiligo outright, because the cause is a combination of genetic susceptibility and triggers that cannot all be controlled. Practical prevention focuses on avoiding and monitoring complications:

• Avoid triggers where possible: protect skin from trauma, friction, sunburn and known phenolic chemicals.
• Screen for thyroid disease and other autoimmune conditions, as outlined above, especially at diagnosis and if symptoms develop later.
• Vitamin D assessment and supplementation where deficient.
• Skin cancer surveillance through routine dermatological care; depigmented skin is sun-sensitive.
• Genetic counselling is sometimes offered for families with strong histories, but risk remains probabilistic. ^[2][9][5]

Children. Vitiligo can begin in early childhood. Topical steroids and calcineurin inhibitors and NB-UVB are used with age-appropriate dosing, and segmental vitiligo is proportionally more common in children. Because the evidence base is limited in those under 18 years, specialist paediatric dermatology input is sensible. Psychological support is particularly important for adolescents. ^[1][4][5]

Pregnancy. Topical calcineurin inhibitors are avoided in pregnancy; systemic treatment requires caution; camouflage and photoprotection remain safe options. Ruxolitinib cream is not recommended in pregnancy. Involve obstetric and dermatology teams for extensive or progressive disease. ^[5][4]

Older adults. Thin skin makes atrophy from prolonged potent steroids more likely, so intermittent regimens and calcineurin inhibitors are preferred on the face and flexures. Polypharmacy and comorbidities guide systemic choices. ^[5][2]

Albinism is not vitiligo: it is a congenital, inherited problem of melanin synthesis rather than an acquired autoimmune destruction of melanocytes. Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders with reduced or absent melanin in skin, hair and eyes, occurring in roughly 1 in 17,000 people worldwide (about 1 in 70 is a carrier). The commonest and most severe form, OCA1A (tyrosinase-negative), produces a complete lifelong absence of pigment; milder forms (OCA1B, OCA2, OCA3, OCA4) accumulate some pigment over time. Clinical features include congenital nystagmus, iris transillumination, foveal hypoplasia, reduced visual acuity (usually 20/60 to 20/400), photophobia, strabismus and a high risk of sunburn and skin cancer; life span, development, intelligence and fertility are normal. Management is supportive: refractive correction and dark or photochromic lenses, correction of strabismus and nystagmus, strict sun protection (sunscreens, protective clothing) and regular skin checks for early cancer. No curative treatment exists. Piebaldism, another congenital, stable differential, shows a white forelock and midline depigmentation present from birth that does not change. ^[7][5]

Melasma is, in a sense, the opposite problem to vitiligo: an acquired, symmetric increase in pigmentation (hypermelanosis) rather than a loss. It is common, affects 1 to 50% of higher-risk populations depending on ethnicity, and is more common in females (female to male ratios from 4 to 1 up to 39 to 1 in different series) and in darker skin types. ^[8] Onset is typically between 20 and 30 years of age. The characteristic pattern is reticulated brown patches on the centrofacial area (forehead, nose, cheeks) or malar region. Triggers include ultraviolet and visible light, female sex hormones (pregnancy, oral contraceptives) and a family history (55 to 64% of patients). Histologically the pigment may be epidermal, dermal or mixed; a Wood's lamp accentuates epidermal pigment but can be misleading in dermal disease. ^[8]

Treatment follows the same staged, combined approach, led by photoprotection ^[8]:

• Photoprotection first: broad-spectrum sunscreen that also blocks visible light (iron oxide-containing formulations) because visible light alone can drive pigmentation.
• Topical therapy is first line: hydroquinone 4% (the most studied agent), azelaic acid, kojic acid, ascorbic acid, niacinamide, tretinoin, or triple-combination cream (hydroquinone 4% + tretinoin 0.05% + fluocinolone 0.01%), which outperformed hydroquinone alone in a trial of 260 Asian patients, though with more irritation.
• Oral agents such as tranexamic acid (with venous thrombosis risk screening) are effective in many patients.
• Procedures (chemical peels, microneedling, lasers) are useful adjuncts combined with topical therapy and photoprotection.
• Camouflage (concealers with UV blockers) improves quality of life immediately while slower treatments take effect.

Melasma is not caused by melanocyte loss and does not carry the autoimmune associations of vitiligo; it can, however, be confused with post-inflammatory pigment change. ^[8]

• Vitiligo is an acquired autoimmune loss of melanocytes producing chalk-white patches, driven by oxidative stress and CD8-positive T-cell attack via interferon gamma and JAK-STAT signalling.
• Non-segmental vitiligo is 80 to 90% of cases and carries the autoimmune associations; segmental vitiligo is unilateral, early-onset and usually stable.
• Prevalence 0.5 to 2% worldwide; up to 30% have a family history; 20% of patients over 20 years have thyroid disease.
• A Wood's lamp is the key bedside tool for finding and mapping depigmented skin.
• Screen thyroid function and TPO antibodies; extend the autoimmune screen only when symptoms suggest it.
• First-line therapy: potent or very potent topical corticosteroid once daily, or topical calcineurin inhibitor (tacrolimus 0.03/0.1% or pimecrolimus) twice daily for face and flexures; review every 3 to 6 months.
• NB-UVB (2 to 3 sessions per week, minimum 12 weeks, often 12 or more months) for extensive or active disease; about 36% achieve at least 75% repigmentation after 12 months, best on the face and neck.
• Ruxolitinib cream, a topical JAK inhibitor, is the first disease-specific repigmenting cream approved: age 12 years or older, non-segmental vitiligo, thin layer twice daily, with about 30% reaching 75% repigmentation and 15% reaching 90% repigmentation at week 24; reassess if no response in 24 weeks.
• Maintenance therapy helps preserve repigmentation; about 40% of patients lose some colour within a year of stopping.
• Surgery is reserved for stable, treatment-resistant patches; depigmentation is a last resort for extensive disease.
• Albinism is congenital loss of melanin synthesis (about 1 in 17,000, autosomal recessive, no cure); melasma is acquired pigment excess driven by UV/visible light and hormones.
• Follow published guidelines (BAD vitiligo guideline 2021, AAD, NICE CKS, StatPearls) and check your local formulary.

Autoimmune thyroid disease; pigmentary dermatoses and genetic disorders of melanin synthesis; skin cancer screening and photoprotection; atopic eczema and post-inflammatory hypopigmentation; counselling and quality-of-life assessment in chronic skin disease.