Dermatology · PANCE / PANRE

Vitiligo

Acquired autoimmune depigmenting disorder with discrete milky-white macules and patches due to melanocyte loss.

Also known as: vitiligo, leukoderma, depigmentation

Overview

An acquired chronic depigmenting disorder of the skin and mucous membranes characterized by well-demarcated milky-white macules and patches resulting from progressive loss of functional epidermal melanocytes.

Epidemiology

Worldwide prevalence ~0.5-2%. Onset before age 20 in 50%. No sex or racial predilection, but psychosocial impact greater in skin of color. Family history in ~20%.

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Risk factors

  • Polygenic inheritance (NLRP1, PTPN22, TYR, HLA, FOXP3 loci)
  • Personal or family history of autoimmune disease: thyroid (most common — Hashimoto, Graves), pernicious anemia, Addison disease, type 1 diabetes, alopecia areata, rheumatoid arthritis
  • Koebner phenomenon — trauma, friction, sunburn at sites of skin injury
  • Stress (anecdotal)
  • Chemical exposure (phenol derivatives, monobenzone — chemical leukoderma)

Pathophysiology

Autoimmune destruction of melanocytes by CD8+ cytotoxic T-cells targeting melanocyte antigens (tyrosinase, MART-1, gp100). Interferon-γ-driven CXCL9/CXCL10 chemokines recruit autoreactive T-cells. Oxidative stress (impaired antioxidant defenses in melanocytes) and intrinsic melanocyte fragility contribute. JAK-STAT pathway central — basis for new topical JAK inhibitor therapy.

Clinical presentation

Symptoms

  • Most often asymptomatic; mild pruritus at active edges in some patients
  • Psychosocial distress, depression, anxiety, decreased quality of life — especially in skin of color and visible areas

Signs / physical exam

  • Well-demarcated milky-white (chalk-white) macules and patches — completely depigmented (vs hypopigmented)
  • Distribution patterns:
  • • Non-segmental (most common, 85-90%): symmetric, on periorificial face (around eyes, mouth), dorsal hands, axillae, genitalia, elbows, knees; progressive course
  • • Segmental: unilateral, dermatomal or quasi-dermatomal distribution; younger patients; rapid early progression then stable
  • • Acrofacial: face, dorsal hands and feet; common variant
  • • Universal: >80% BSA depigmentation
  • Wood's lamp examination: bright milky-white fluorescence highlights subclinical lesions
  • Leukotrichia (white hairs) within patches — poor prognostic sign for repigmentation
  • Confetti-like depigmentation = active rapid progression

Classic findings

Symmetric, well-demarcated, completely depigmented macules around eyes, mouth, hands, and genitalia — accentuated under Wood's lamp.

Differential diagnosis

  • Tinea versicolor — Hypopigmented finely scaling macules on trunk; KOH 'spaghetti and meatballs'; Wood's lamp pale yellow
  • Pityriasis alba — Ill-defined hypopigmented patches on face of children with atopy; mild scale; partial pigment loss
  • Post-inflammatory hypopigmentation — History of preceding dermatitis/inflammation; not completely depigmented
  • Tuberous sclerosis — Ash-leaf macules present at birth; epilepsy, intellectual disability, facial angiofibromas, shagreen patch
  • Halo nevus — Pigmented nevus with surrounding depigmented ring; benign
  • Idiopathic guttate hypomelanosis — Multiple small (2-5 mm) hypopigmented macules on sun-exposed extremities in older adults
  • Lichen sclerosus — Porcelain-white atrophic plaques, especially genital and figure-of-eight perianal
  • Hypopigmented mycosis fungoides — Adult-onset hypopigmented patches refractory to therapy; biopsy

Diagnostic workup

Diagnostic criteria

Clinical: characteristic acquired depigmented macules ± Wood's lamp confirmation.

Labs

  • Clinical diagnosis — Wood's lamp confirms depigmentation
  • TSH and TPO antibodies (screen autoimmune thyroid disease) at diagnosis and periodically (every 1-2 years)
  • Consider CBC, B12, vitamin D, ANA based on symptoms/risk
  • Skin biopsy rarely needed: absence of melanocytes on H&E and S-100/MART-1 stains

Imaging

  • Not indicated

Diagnostic algorithm

PatternDistributionCourse / Therapy Notes
Non-segmental (85-90%)Symmetric — periorificial, hands, axillae, genitaliaProgressive; NBUVB + topical ruxolitinib / TCI / steroid
SegmentalUnilateral, dermatomalYounger; early rapid then stable; good surgical candidate
AcrofacialFace + dorsal hands/feetCommon variant; similar to non-segmental
Universal>80% BSA depigmentedConsider depigmentation therapy (MBEH)
MucosalLips, genitaliaOften refractory to topicals; JAK inhibitor, NBUVB targeted
Vitiligo clinical patterns and management considerations.

Treatment

First-line

  • Topical corticosteroids: high-potency (clobetasol 0.05%, betamethasone dipropionate 0.05%) BID × 2-4 months for limited disease — pulse therapy (e.g., 2 weeks on / 2 weeks off) to limit atrophy
  • Topical calcineurin inhibitors: tacrolimus 0.1% ointment BID — preferred for face/intertriginous (no atrophy); equally effective as topical steroids in many trials
  • Topical JAK inhibitor: ruxolitinib 1.5% cream BID (FDA-approved 2022 for nonsegmental vitiligo ages ≥12) — significant repigmentation in 50% by 6-12 months
  • Narrowband UVB phototherapy (311-313 nm) 2-3x/week — first-line for widespread disease; combine with topicals for additive effect
  • Excimer laser (308 nm) for localized lesions
  • Sunscreen daily — protect depigmented areas (no melanin protection) and reduce contrast with surrounding skin
  • Cosmetic camouflage: self-tanners (dihydroxyacetone), tinted concealers, micropigmentation

Rapidly progressive / active vitiligo

  • Short courses of oral minipulse corticosteroids (dexamethasone 2.5 mg on 2 consecutive days/week × 3-6 months) to halt progression
  • Combine with NBUVB phototherapy

Stable segmental or localized

  • Surgical melanocyte transplantation: punch grafting, suction blister grafting, melanocyte-keratinocyte transplantation
  • Best results in stable disease >1 year, segmental disease, and areas with intact hair pigment

Extensive (>50% BSA)

  • Depigmentation therapy: monobenzyl ether of hydroquinone (MBEH) 20% cream — permanent depigmentation of remaining pigmented skin for cosmetic uniformity
  • Irreversible — counsel extensively

Second-line / adjunct

  • Afamelanotide (α-MSH analog) + NBUVB — promising in trials
  • Oral JAK inhibitors (ritlecitinib, upadacitinib) — emerging evidence
  • Antioxidants (ginkgo biloba, vitamin E, polypodium leucotomos) — limited evidence
  • Mental health support, vitiligo support groups; address quality of life as actively as the skin disease

Complications

  • Sunburn and increased risk of skin cancer in depigmented areas (though epidemiologic studies surprisingly show LOWER skin cancer rates in vitiligo patients, possibly from increased sun-protective behavior and altered immunity)
  • Psychosocial: depression, anxiety, social isolation, low self-esteem, sexual dysfunction
  • Associated autoimmune diseases — particularly autoimmune thyroid disease
  • Ocular: uveitis, iritis, retinal pigmentary abnormalities (Vogt-Koyanagi-Harada syndrome)
  • Hearing: sensorineural hearing loss (rare; melanocyte loss in inner ear)

PANCE pearls

  • Wood's lamp examination is the bedside test — depigmented vitiligo glows milky-white; hypopigmented conditions (versicolor, post-inflammatory) do not.
  • Screen all vitiligo patients for autoimmune thyroid disease at diagnosis and periodically.
  • Topical ruxolitinib (JAK inhibitor) is now first-line for nonsegmental vitiligo — significant cultural shift in vitiligo therapy since 2022 FDA approval.
  • Leukotrichia (white hairs in patch) predicts poor repigmentation response because hair follicle melanocyte reservoir is depleted.
  • Vitiligo is not 'just cosmetic' — its psychosocial impact often exceeds objective severity; address mental health proactively.

References

  • AAD 2023 — Joint AAD-NPF-Vitiligo Working Group Updated Recommendations for the Management of Vitiligo (Rosmarin et al., J Am Acad Dermatol)
  • VGICC 2023 — Vitiligo Global Issues Consensus Conference Guidelines (Taïeb et al., Br J Dermatol; updated)
  • FDA Ruxolitinib — FDA Approval of Topical Ruxolitinib 1.5% Cream for Nonsegmental Vitiligo (2022)

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