Vitiligo

Meet the patient

A 28-year-old woman returns to clinic with chalk-white patches spreading symmetrically across her dorsal hands, around her eyes, and over her neck over four months. New lesions appeared in a line where a new handbag strap rubbed her shoulder, and her mother takes levothyroxine for Hashimoto thyroiditis.[1]

Two questions decide her next year, and they are the two that decide every vitiligo case: is this segmental or non-segmental? and is the disease active or stable? Classify first, then grade activity, and the entire management ladder falls out underneath.[1][3]

The fork that decides everything — segmental or not?

Classify before you treat, because the wrong class earns the wrong drug and the wrong prognosis. The Vitiligo Global Issues Consensus Conference swept away the old focal, generalised, acral soup and replaced it with a mechanistic split that examiners now expect verbatim.[3]

Non-segmental vitiligo (NSV) is the common phenotype — bilateral, symmetrical, autoimmune, prone to progress and relapse. Segmental vitiligo (SV) is unilateral and dermatomal or Blaschkoid, begins early, races for a year and then burns out and stabilises — which is precisely why SV is the best surgical candidate and the worst responder to open-ended medical therapy.[1]

[1] [3]

The classic trap: a single asymmetrical patch tempts every candidate to write "focal vitiligo" and move on. Focal is now an unclassified holding pen — most patches declare themselves NSV or SV within a year or two, so you reclassify as the pattern evolves rather than locking in a dead label.[3]

The cluster rule for NSV subtypes — V-A-M-U: Vulgaris (widespread symmetrical), Acrofacial (digits and periorificial), Mucosal, Universal (most of the body surface). One image, four subtypes, no list to forget.[1]

How common, who, and why the contrast hurts

About one person in a hundred has vitiligo — global prevalence sits around 0.5 to 2 percent, with no sex predilection and roughly half of patients beginning before age 20. The disease is colour-blind at the level of the melanocyte but not at the level of the patient: the chalk-white patch is far more visible, and far more stigmatising, on darker skin.[1][4]

Family history is positive in roughly one in five, and the susceptibility loci read like an autoimmune roll-call — HLA, PTPN22, NLRP1, XBP1, TYR, PMEL — shared architecture that explains why vitiligo travels in company with thyroid disease, type 1 diabetes, and alopecia areata.[5]

The psychological burden is the disease, not a footnote to it. Vitiligo's DLQI sits in the same range as psoriasis and atopic dermatitis, with depression, anxiety, social phobia, and sexual dysfunction all over-represented — so screen with PHQ-9 and GAD-7 at diagnosis, not when the patient breaks down in the room.[10]

Why the melanocyte dies — the IFN-γ / JAK-STAT axis

Vitiligo is the cleanest autoimmune skin disease we teach, because one signalling axis explains both the disease and its newest drug. Autoreactive CD8+ T-cells recognise melanocyte antigens — tyrosinase, Melan-A/MART-1, gp100 — and release interferon-gamma (IFN-γ); IFN-γ fires JAK1/JAK2-STAT signalling in nearby keratinocytes, driving CXCL9 and CXCL10, which recruit yet more CD8+ cells in a self-amplifying loop until the melanocyte is gone.[5]

Follow that chain and you have written the rationale for topical ruxolitinib. A JAK1/JAK2 inhibitor blocks the very signal driving the disease — which is why a cream, not just a light, can repigment vitiligo.[5]

Etymology for viva gold: vitiligo is from the Latin vitium, a blemish or mark — and melanocyte from Greek melas, black, plus kytos, a cell. The disease outlived its stigma; the names outlived their metaphors.[1]

The chain has two accomplices worth naming at viva depth. Oxidative stress — reactive oxygen species from defective antioxidant defences damage melanocytes and unmask their antigens, lighting the autoimmune fuse; variants in XBP1 (endoplasmic-reticulum stress) and NLRP1 (inflammasome) mark susceptibility. The melanocyte reservoir lives in the hair-follicle bulge, which is the entire reason hairy skin repigments and glabrous skin does not.[5][6]

What juniors forget: repigmentation under treatment appears perifollicular — tiny freckles of pigment ringing each hair — because that is the stem cell marching outward. Perifollicular repigmentation means the treatment is working; absence of follicles on fingertips and lips means the treatment never will.[6]

Read the skin — activity predicts everything

A chalk-white, well-demarcated macule with convex borders is vitiligo until proven otherwise; the exam prize is spotting active disease, because active disease changes the whole plan. Three signs mean the fire is still burning:[1]

• Trichrome vitiligo — three concentric zones: normal skin, a grey intermediate halo, chalk-white centre. The intermediate zone is melanocytes dying in real time.[1]
• Confetti macules — tiny depigmented specks that forecast coalescent patches.[1]
• Koebner phenomenon — new vitiligo along a line of trauma, friction, burn, or surgery. The handbag-strap line on the patient in the vignette is Koebner, and Koebner is active disease by definition.[7]

The activity rule — 6 and 12. Active means new lesions or enlargement within the last 3 to 6 months; stable means no new lesions and no enlargement for at least 6 to 12 months. Stability is not bookkeeping — it is the gate to surgery, because melanocytes transplanted into burning disease are destroyed and the graft re-depigments.[2]

The mimics — congenital beats acquired, every time

Before you commit to vitiligo, ask one question: was the patch there at birth? The onset history is the single most powerful discriminator in depigmentation, and it sorts the entire differential in one breath.[4]

[1] [4] [1] [4]

The discriminator line: congenital plus stable is naevus depigmentosus, ash-leaf macule, or piebaldism; acquired plus progressive is vitiligo until proven otherwise. Wood lamp alone cannot separate them — the onset history, family history, and any syndrome features are the deciding evidence.[4]

The Wood lamp — your one bedside tool

The Wood lamp turns a clinical hunch into a defensible boundary. It emits long-wave UVA at approximately 365 nm; depigmented skin, with no melanin to absorb the UV, glows chalk-white or bright blue-white, while merely hypopigmented skin glows off-white or tan. That single contrast separates true depigmentation from hypopigmentation at the bedside.[4]

Practical technique: dim the room, hold the lamp 10 to 15 cm from the skin, and wait 30 to 60 seconds for your eyes to dark-adapt. Use it to delineate true extent in fair skin, to catch subclinical lesions invisible in daylight, and to watch perifollicular repigmentation creep in under treatment.[1]

The classic trap: the Wood lamp does not diagnose vitiligo — erythrasma glows coral-red, tinea capitis green, porphyria urine pink. Vitiligo remains a clinical diagnosis, with the lamp as support and biopsy reserved for the atypical case.[4]

When the picture is not classic, biopsy. Histology shows absent or markedly reduced melanocytes and melanin in the basal layer with a superficial perivascular lymphocytic infiltrate in early lesions; Melan-A, S100, or SOX10 stains confirm the melanocyte loss.[4]

Measure it before you treat it

You cannot follow what you do not score. Three validated instruments anchor every vitiligo consultation and every trial endpoint — know them by name and purpose.[2]

[8] [9] [10]

The practical severity bands: limited is under about 1 percent body surface area, generalised is 1 to 10 percent, extensive is over 10 percent or universal, and the special sites — face, hands, feet, genitalia, mucosae — earn targeted therapy regardless of total area.[1][2]

The thyroid is always the question — comorbidity screening

Vitiligo is one of the most consistent cutaneous markers of systemic autoimmunity, so screen even the asymptomatic patient. A 2023 systematic review and meta-analysis confirmed increased prevalence of a cluster of autoimmune diseases, and the screening panel follows directly from that risk.[11]

Autoimmune thyroid disease is the headline association — present in roughly 20 to 30 percent of vitiligo patients overall and up to 40 to 50 percent in adults over 40 — followed by type 1 diabetes, pernicious anaemia, alopecia areata, Addison disease, inflammatory bowel disease, psoriasis, rheumatoid arthritis, and SLE.[1][11]

The minimum panel at diagnosis:[2]

• TSH, with anti-TPO if abnormal — autoimmune thyroid disease is the commonest and the most insidious association; repeat annually or with new symptoms.[11]
• Fasting glucose or HbA1c — type 1 diabetes and glucose intolerance, especially with a positive family history.[11]
• Vitamin B12, folate, and red-cell indices — pernicious anaemia, above all with macrocytosis or neuropathy.[11]
• ANA — only if systemic lupus or Sjögren syndrome is clinically suspected; do not fish blindly.[11]
• Morning cortisol or ACTH-stimulation test — only if Addison disease is on the differential (fatigue, hyperpigmentation elsewhere, hyponatraemia).[11]

[11]

Topical first — and the face gets calcineurin, not steroid

Limited, localised, or facial disease starts topical, and the site picks the agent. Potent corticosteroids win on trunk and limbs; calcineurin inhibitors own the face, eyelids, flexures, and genitalia because they repigment without atrophy.[1]

[1] [2]

The site rule — trunk and limbs get steroid, face and flexures get calcineurin. A potent steroid on the eyelids for three months earns telangiectasia and atrophy and loses marks; tacrolimus 0.1 percent twice daily does the same job safely, and pimecrolimus 1 percent is first-line wherever skin is thin.[1]

[1] [2] [12] [13]

Ruxolitinib — the first drug built for this axis

Topical ruxolitinib 1.5 percent is the first therapy approved specifically for non-segmental vitiligo, and it was designed from the pathophysiology upward. The phase 2 trial and the two phase 3 TRuE-V1 and TRuE-V2 trials showed significantly greater facial and total-body repigmentation than vehicle at 24 weeks, with continued gain to 52 weeks; it is applied twice daily to affected areas up to about 20 percent body surface area.[21][22]

The combination insight: adding NB-UVB to ruxolitinib outperforms ruxolitinib alone, so for extensive non-segmental disease the modern move is JAK inhibition plus light, not either in isolation.[23]

Light is a drug — NB-UVB first, PUVA last

Phototherapy is first-line for widespread or rapidly progressive non-segmental vitiligo, and narrowband UVB is the wavelength of choice. NB-UVB at 311 nm is given two to three times weekly for at least 6 to 12 months, repigments perifollicularly, and works best on the face and trunk; meta-analysis confirms it is effective, with combination therapy generally beating monotherapy.[14]

The 308 nm excimer laser targets localised stable lesions — especially on the face and neck — and is usually paired with topical tacrolimus or steroid; a network meta-analysis supports excimer combination therapy, above all for facial vitiligo.[27]

PUVA — oral or topical psoralen plus UVA — works but is now second-line, because the cumulative UVA dose carries long-term photocarcinogenesis risk. Reserve it for patients who cannot attend frequent NB-UVB sessions or for selected refractory cases.[15]

The combination that earns marks: tacrolimus plus NB-UVB produces higher repigmentation than NB-UVB alone — so when the disease is widespread enough to need light, add a topical calcineurin inhibitor to the same regimen.[16]

Stop the fire — systemic stabilisation for active disease

When vitiligo is racing — new lesions weekly — a topical will not keep up, and systemic therapy exists to halt progression, not to repigment. Repigment later; stabilise now.[17]

Oral mini-pulse dexamethasone — roughly 2.5 to 5 mg on two consecutive days each week — is the workhorse for active disease, with randomised-trial evidence that it halts progression; it is the dose that anchors the exam stem. A short tapering course of oral prednisolone at about 0.3 to 0.5 mg/kg/day is an alternative for explosive spread, balanced against metabolic and infectious harm.[17][18]

Ciclosporin at about 2 to 4 mg/kg/day stabilised active vitiligo in a randomised trial — monitor blood pressure and renal function, and avoid long courses. Low-dose methotrexate at about 10 to 25 mg weekly has been reported to stabilise refractory disease; monitor full blood count, liver function, and renal function, and give folic acid.[19][20]

Azathioprine, mycophenolate mofetil, and oral JAK inhibitors (ruxolitinib, tofacitinib) are used off-label in refractory cases under specialist oversight — name them, then defer to the dermatologist.[1][12]

Surgery only when the fire is out

Surgical repigmentation is the reward for stability, and stability means at least 6 to 12 months of no new lesions and no Koebner. Transplant melanocytes into burning disease and the immune process destroys them — the graft re-depigments and the patient loses trust.[2]

Autologous non-cultured melanocyte-keratinocyte transplantation is the workhorse: harvest a thin split-thickness graft, trypsinise it into a cell suspension, and apply it to the dermabraded recipient site — best for larger stable patches, with good repigmentation on suitable sites. Suction-blister, punch, cultured-melanocyte, and hair-follicle grafts fill the smaller or specialised niches.[24]

Best responders: segmental vitiligo, small stable lesions, face and neck, adults without Koebner. Poor responders: active disease, acral sites with sparse follicular reservoirs, large non-segmental patches, and patients expecting a perfect colour match in weeks.[24]

When all else fails, take the rest away — depigmentation

For extensive or universal vitiligo — generally over 50 percent body surface area — that has failed repigmentation, depigmentation with monobenzone removes the remaining pigment to reach a uniform pale complexion. It is permanent, it demands lifelong sun protection, and it is psychologically momentous; counsel carefully before offering it, and never as a shortcut.[25]

Children, pregnancy, and the frightened patient

In children, prefer calcineurin inhibitors and NB-UVB, and treat the stigma as aggressively as the skin. Childhood vitiligo is often segmental or focal, calcineurin inhibitors spare the face from steroid atrophy, NB-UVB is safe and effective, and school-related bullying makes psychological support non-optional.[26]

In pregnancy, most systemic agents are off the table. Lean on topical corticosteroids and calcineurin inhibitors over limited areas, continue phototherapy with abdominal and eye shielding, and avoid methotrexate and ciclosporin unless a specialist insists. The same caution applies to breastfeeding.[1][2]

The mantra, and what repigments

The mantra: classify, grade activity, calm the fire, repigment from the follicle, screen the thyroid, support the person.[1]

Favourable prognosis: recent onset, facial involvement, darker phototype, hairs within lesions. Unfavourable: long-standing disease, acral and mucosal lesions, segmental vitiligo under medical therapy, and prior extensive depigmentation. Face, neck, and trunk repigment well; hands, feet, lips, and genitalia repigment poorly — and the reason is always the hair-follicle melanocyte reservoir.[1][6]

Relapse is the rule after stopping therapy, so plan maintenance and set expectations honestly at the first visit. Follow topical response at 8 to 12 weeks, phototherapy every 3 to 4 months with photography, and systemic therapy on the monitoring schedule the drug demands.[1][2]

[1] [1]

Ward-round test

Stem 1 — A 30-year-old man has chalk-white patches appearing symmetrically on his hands and face over three months, with new lesions along a recent surgical scar. What is the phenomenon, what does it signal, and what does it change in your plan?[7]

Answer

That is Koebner phenomenon — vitiligo appearing along a line of trauma. It signals active disease, which means surgery is off the table until the disease has been stable for at least 6 to 12 months; the priority now is stabilisation, typically an oral mini-pulse steroid, plus a topical calcineurin inhibitor for the face.[7][2]

Stem 2 — A fair-skinned 8-year-old has a solitary off-white patch on the trunk present since birth. Wood lamp enhances it but it stays off-white, not chalk-white. Vitiligo or not — and what must you exclude?[4]

Answer

Not vitiligo — the lesion is congenital, stable, and hypopigmented (off-white), not depigmented (chalk-white), which fits an ash-leaf macule, the cutaneous marker of tuberous sclerosis (TSC1/TSC2). Examine for angiofibromas, shagreen patch, periungual fibromas, epilepsy, and renal angiomyolipomata, and refer for a genetics work-up if multiple lesions or syndrome features are present.[4]

Stem 3 — A patient with widespread non-segmental vitiligo asks why the cream is not working on her fingertips and lips while her face is repigmenting well. Give the mechanistic answer in one sentence.[6]

Answer

Repigmentation comes from melanocyte stem cells in the hair-follicle bulge migrating outward as perifollicular pigment; the face has hair follicles, so it repigments, while the fingertips and lips are glabrous skin without follicular reservoirs, so no stem-cell source exists to recolonise them.[6]

Stem 4 — Name the signalling axis that drives vitiligo, the chemokines at its centre, and the drug class that targets it.[5]

Answer

CD8+ T-cells release IFN-γ, which activates the JAK1/JAK2-STAT pathway in keratinocytes, driving CXCL9 and CXCL10 that recruit more CD8+ cells and destroy melanocytes. The drug class that breaks the loop is the topical JAK inhibitors, of which ruxolitinib 1.5 percent is the approved agent for non-segmental vitiligo.[5][22]

References

1. [1]Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo Lancet, 2015.PMID 25596811
2. [2]Eleftheriadou V, Atkar R, Batchelor J, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021 Br J Dermatol, 2022.PMID 34160061
3. [3]Ezzedine K, Lim HW, Suzuki T, Katayama I. Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference Pigment Cell Melanoma Res, 2012.PMID 22417114
4. [4]Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up J Am Acad Dermatol, 2011.PMID 21839315
5. [5]Mukhatayev Z, Le Poole IC. Vitiligo: advances in pathophysiology research and treatment development Trends Mol Med, 2024.PMID 38705825
6. [6]Birlea SA, Costin GE, Roop DR, Norris DA. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization Med Res Rev, 2017.PMID 28029168
7. [7]van Geel N, Speeckaert R, Taieb A, et al. Koebner's phenomenon in vitiligo: European position paper Pigment Cell Melanoma Res, 2011.PMID 21324101
8. [8]Taïeb A, Picardo M The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force Pigment Cell Res, 2007.PMID 17250545
9. [9]Ceresnie MS, Warbasse E, Gonzalez S, et al. Implementation of the vitiligo area scoring index in clinical studies of patients with vitiligo: a scoping review Arch Dermatol Res, 2023.PMID 37029284
10. [10]Morales-Sánchez MA, Vargas-Salinas M, Peralta-Pedrero ML, et al. Impact of Vitiligo on Quality of Life Actas Dermosifiliogr, 2017.PMID 28456327
11. [11]Lee JH, Ju HJ, Seo JM, et al. Comorbidities in Patients with Vitiligo: A Systematic Review and Meta-Analysis J Invest Dermatol, 2023.PMID 36574529
12. [12]Ezzedine K, Whitton M, Pinart M. Interventions for Vitiligo JAMA, 2016.PMID 27784078
13. [13]Whitton ME, Pinart M, Batchelor J, et al. Interventions for vitiligo Cochrane Database Syst Rev, 2015.PMID 25710794
14. [14]Bae JM, Jung HM, Hong BY, et al. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis JAMA Dermatol, 2017.PMID 28355423
15. [15]Shenoi SD, Prabhu S Photochemotherapy (PUVA) in psoriasis and vitiligo Indian J Dermatol Venereol Leprol, 2014.PMID 25382505
16. [16]Dong Y, Yang Q, Guo B, et al. The effects of tacrolimus plus phototherapy in the treatment of vitiligo: a meta-analysis Arch Dermatol Res, 2021.PMID 32785837
17. [17]El Mofty M, Essmat S, Youssef R, et al. The role of systemic steroids and phototherapy in the treatment of stable vitiligo: a randomized controlled trial Dermatol Ther, 2016.PMID 27528547
18. [18]Singh A, Kanwar AJ, Parsad D, et al. Randomized controlled study to evaluate the effectiveness of dexamethasone oral minipulse therapy versus oral minocycline in patients with active vitiligo vulgaris Indian J Dermatol Venereol Leprol, 2014.PMID 24448120
19. [19]Mehta H, Kumar S, Parsad D, Kumaran MS. Oral cyclosporine is effective in stabilizing active vitiligo: Results of a randomized controlled trial Dermatol Ther, 2021.PMID 34151493
20. [20]Tavitova A, Valle Y, Lomonosov K. Using methotrexate in the treatment of advanced vitiligo J Cosmet Dermatol, 2023.PMID 36409563
21. [21]Rosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial Lancet, 2020.PMID 32653055
22. [22]Rosmarin D, Passeron T, Pandya AG, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo N Engl J Med, 2022.PMID 36260792
23. [23]Pandya AG, Harris JE, Lebwohl M, et al. Addition of Narrow-Band UVB Phototherapy to Ruxolitinib Cream in Patients With Vitiligo J Invest Dermatol, 2022.PMID 35787401
24. [24]Bassiouny D, Esmat S. Autologous non-cultured melanocyte-keratinocyte transplantation in the treatment of vitiligo: patient selection and perspectives Clin Cosmet Investig Dermatol, 2018.PMID 30464567
25. [25]Grimes PE, Nashawati R. Depigmentation Therapies for Vitiligo Dermatol Clin, 2017.PMID 28317530
26. [26]Nicolaidou E, Mastraftsi S, Tzanetakou V, et al. Childhood Vitiligo Am J Clin Dermatol, 2019.PMID 30911977
27. [27]Li C, Hu Y, Mu Z, et al. Comparison of various excimer laser (EL) combination therapies for vitiligo: a systematic review and network meta-analysis J Dermatolog Treat, 2024.PMID 38230424