Vitiligo

Vitiligo is an acquired, idiopathic, autoimmune depigmenting disorder caused by selective destruction of epidermal melanocytes, producing sharply demarcated chalk-white macules and patches. It is a favourite NEET PG topic because it combines a classic clinical picture (Wood's lamp accentuation, Koebner phenomenon), strong autoimmune associations, and a tiered treatment ladder from topical steroids to melanocyte transplantation.

Definition and overview

Vitiligo is defined as a chronic, acquired pigmentary disorder characterised by well-circumscribed, milky/chalk-white macules and patches resulting from progressive loss of functioning melanocytes from the epidermis (and sometimes the hair follicle and mucosae). It affects roughly 0.5–2% of the world population, with a notably high prevalence in India (often quoted around 3–4% in some series), and carries a substantial psychosocial burden in pigmented skin where the contrast is striking.

There is no sex predilection (slight female reporting bias due to cosmetic concern). Onset peaks in the second and third decades, and about half present before age 20. A positive family history is present in ~20–30%, with inheritance being polygenic/multifactorial, not simple Mendelian.

High-yield: Vitiligo = acquired loss of melanocytes → depigmented (NOT merely hypopigmented) macules that are chalk-white / milky-white and show fluorescent bright blue-white accentuation under Wood's lamp.

Classification

The most exam-relevant split is segmental vs non-segmental, formalised by the Vitiligo Global Issues Consensus Conference (VGICC, 2012).

Feature	Segmental vitiligo (SV)	Non-segmental vitiligo (NSV)
Distribution	Unilateral, blaschkoid/dermatomal-like, does not cross midline	Bilateral, often symmetrical
Age	Younger (childhood common)	Any age, peaks 2nd–3rd decade
Course	Rapid spread early, then stabilises	Chronic, unpredictable, progressive
Leukotrichia (white hair)	Early and common	Later
Autoimmune association	Weak	Strong (thyroid etc.)
Koebner phenomenon	Usually absent	Present
Response to medical Rx	Poorer	Better; surgery good for stable SV

Non-segmental subtypes: focal, acrofacial, mucosal, generalised (vulgaris), and universalis (>80–90% body surface depigmentation). Mixed vitiligo = coexisting segmental + non-segmental.

High-yield: Segmental vitiligo is unilateral, stable, has early leukotrichia, responds poorly to medical therapy but is the BEST candidate for surgical melanocyte transplantation.

Etiology and pathophysiology

Vitiligo is best understood as a convergence theory disorder — multiple mechanisms culminate in melanocyte loss. The dominant accepted mechanism is autoimmune.

Key mechanisms:

1. Autoimmune (most accepted): CD8+ cytotoxic T cells target melanocyte antigens (tyrosinase, MART-1, gp100). IFN-γ → CXCL9/CXCL10 → CXCR3+ T-cell recruitment is the central inflammatory axis (basis for JAK inhibitors). Anti-melanocyte autoantibodies are detectable.
2. Oxidative stress / biochemical: Accumulation of hydrogen peroxide (H₂O₂) and reactive oxygen species, with low epidermal catalase, damages melanocytes and exposes neoantigens.
3. Neural hypothesis: Neurochemical mediators from nerve endings are toxic to melanocytes — invoked especially to explain segmental (dermatomal) distribution.
4. Genetic susceptibility: Polygenic; associations with HLA, NLRP1, PTPN22, and notably the melanocyte gene TYR (tyrosinase) — interestingly TYR risk allele protects against melanoma.
5. Melanocytorrhagy / defective adhesion: Detachment and transepidermal loss of melanocytes, accentuated by friction (explains Koebner).

High-yield: The IFN-γ–CXCL10–CXCR3 signalling axis driving CD8+ T-cell attack is the rationale for topical/oral JAK inhibitors (ruxolitinib, ritlecitinib) — a hot, recently tested concept.

Histopathology: Complete absence of melanocytes and melanin in established lesions (confirmed by Fontana-Masson and immunostains MART-1/Melan-A, HMB-45, S-100, c-kit). Lymphocytic infiltrate may be seen at the advancing border.

Associated autoimmune conditions

Vitiligo travels with other organ-specific autoimmune diseases; screening is a classic exam point.

Association	Relevance
Autoimmune thyroid disease (Hashimoto's > Graves')	Most common; screen with TSH ± anti-TPO antibodies
Type 1 diabetes mellitus	Increased frequency
Pernicious anaemia	Anti-parietal cell / IF antibodies
Addison's disease	Component of APS
Alopecia areata	Shared autoimmune basis
Halo naevus (Sutton's naevus)	May precede/accompany
Autoimmune polyglandular syndromes (APS-1, APS-2)	Cluster

High-yield: The single most common associated autoimmune disorder is autoimmune thyroid disease — every new generalised vitiligo patient should get a thyroid profile (TSH + anti-TPO).

Syndromic / special associations to recognise:

• Vogt–Koyanagi–Harada (VKH) syndrome: vitiligo + poliosis + uveitis + alopecia + meningism + dysacusis.
• Alezzandrini syndrome: unilateral facial vitiligo + poliosis + ipsilateral retinitis/visual loss + deafness.
• Schmidt syndrome (APS-2): Addison's + autoimmune thyroid ± T1DM, with vitiligo.

Clinical features

• Lesions: Sharply marginated, depigmented chalk-white macules/patches, usually asymptomatic. Borders may show hyperpigmented rim. Trichrome vitiligo = white–tan–normal zones; quadrichrome / pentachrome add darker/marginal hues; vitiligo ponctué = discrete confetti-like macules.
• Sites of predilection: Periorificial face (peri-oral, peri-ocular), dorsa of hands, fingers, elbows, knees, ankles, genitalia, and areas of friction/trauma. Acral and periorificial pattern is classic.
• Leukotrichia: Depigmentation of hair (eyelashes — poliosis, scalp, body); indicates follicular reservoir involvement → poorer repigmentation prognosis.
• Koebner phenomenon (isomorphic response): New lesions at sites of trauma/friction/sunburn — marker of active/unstable disease.
• Mucosal involvement: Lips, genital mucosa.
• Active disease signs: Koebner, confetti macules, trichrome lesions, and inflammatory/raised erythematous border indicate ongoing activity and likely spread.

High-yield: Koebner phenomenon, confetti-like macules, and trichrome lesions = signs of disease ACTIVITY/instability → favour aggressive medical therapy and contraindicate surgery until stable.

Diagnosis and investigations

Vitiligo is largely a clinical diagnosis. Investigations confirm depigmentation, assess activity, and screen associations.

• Wood's lamp (365 nm UVA): Investigation of choice for highlighting lesions. Depigmented vitiligo glows bright blue-white / chalky and lesions become more sharply demarcated, especially useful in fair skin and to map subclinical/early lesions. Helps distinguish depigmentation (vitiligo) from hypopigmentation.
• Dermoscopy: Perilesional hyperpigmentation, residual perifollicular pigment (good prognostic — follicular reservoir intact), absent pigment network, telangiectasia in steroid-treated/active disease.
• Skin biopsy (rarely needed): Absent melanocytes/melanin; reserved for atypical cases.
• Screening labs: TSH + anti-TPO antibodies (routine), ± FBS/HbA1c, CBC and B12 if symptoms, ANA if features of connective tissue disease. Pre-phototherapy/JAK workup as indicated.

Diagnostic flow:

Chalk-white macule → Wood's lamp (bright blue-white accentuation = depigmentation) → assess segmental vs non-segmental & activity (Koebner/confetti/trichrome) → screen thyroid (TSH/anti-TPO) → biopsy only if atypical → stage & treat

High-yield: Wood's lamp is the bedside investigation of choice: vitiligo shows bright blue-white fluorescence with accentuated sharp margins, distinguishing it from tinea versicolor (yellow-gold), erythrasma (coral-red), and pseudomonas (green).

Management

Goals: arrest progression, stimulate repigmentation, and address psychosocial impact. Therapy is staged by extent, activity, and stability.

Medical therapy (mainstay for NSV)

Modality	Use / notes
Topical corticosteroids (potent, e.g. clobetasol/mometasone)	First-line for limited disease; avoid prolonged use on face/folds (atrophy)
Topical calcineurin inhibitors (tacrolimus 0.1%, pimecrolimus)	First-line for face, eyelids, folds; steroid-sparing, good for periorificial sites
Topical JAK inhibitor — ruxolitinib 1.5% cream	FDA-approved (2022) for non-segmental vitiligo ≥12 yr; targets IFN-γ/JAK-STAT
Narrowband UVB (NB-UVB, 311 nm)	Phototherapy of choice for generalised/widespread disease — safer than PUVA, no psoralen, usable in children & pregnancy
PUVA (psoralen + UVA)	Older; more side effects (nausea, phototoxicity, cataract risk, lentigines) — largely superseded by NB-UVB
Excimer laser (308 nm)	Targeted, ideal for localised/segmental lesions
Systemic mini-pulse steroids (OMP — oral betamethasone/dexamethasone)	To arrest rapidly spreading/active disease
Oral JAK inhibitors (ritlecitinib etc.)	Emerging for extensive disease

High-yield: NB-UVB (311 nm) is the phototherapy of choice for widespread vitiligo — preferred over PUVA because of better safety, efficacy, and use in children/pregnancy. Best repigmentation occurs on the face/neck; worst on acral areas (hands/feet) and over leukotrichia.

Surgical therapy

Reserved for stable disease (no new lesions/spread, no Koebner for ≥6–12 months), refractory to medical therapy — segmental and focal vitiligo are the best responders.

• Tissue grafts: Suction blister epidermal grafting, mini-punch/thin split-thickness grafting.
• Cellular grafts: Non-cultured epidermal cell suspension (Jodhpur/melanocyte–keratinocyte transplantation, MKTP) and cultured melanocyte transplantation.

High-yield: Surgery only in STABLE vitiligo (≥6–12 months no activity); segmental vitiligo is the ideal surgical candidate. Active disease with Koebner is a contraindication (graft itself can Koebnerise).

Depigmentation therapy

For extensive (>50%) recalcitrant disease, depigment the remaining normal skin for uniformity using monobenzyl ether of hydroquinone (monobenzone/MBEH) — this is irreversible.

Adjuncts/cosmetic: camouflage (dihydroxyacetone self-tanners, make-up), strict photoprotection, vitamin D analogues (adjunct to phototherapy), antioxidants, and psychological counselling (high QoL impact).

Treatment ladder (flow):

1. Limited disease → potent topical steroid (body) / topical calcineurin inhibitor (face) ± excimer laser ± topical ruxolitinib.
2. Active/rapidly spreading → oral mini-pulse steroids to halt progression.
3. Generalised/widespread → NB-UVB phototherapy (± topicals).
4. Stable + refractory + segmental/focal → surgical melanocyte transplantation.
5. Extensive recalcitrant (>50%) → depigmentation with monobenzone.

Complications and prognosis

• Psychosocial: depression, anxiety, stigma — major in pigmented skin and in India.
• Sunburn / photodamage of depigmented skin; slightly reduced (not increased) skin cancer risk is reported despite UV vulnerability.
• Ocular/auditory: uveal and retinal pigment involvement (esp. VKH); melanocytes in cochlea → rare hearing changes.
• Leukotrichia → poor repigmentation (loss of follicular melanocyte reservoir).
• Halo naevi and Koebnerisation.

Prognostic pointers: Recent-onset, facial/neck lesions, dark skin, and presence of perifollicular pigment on dermoscopy repigment well; acral lesions, mucosae, leukotrichia, long-standing, and segmental lesions respond poorly to medical therapy.

Key differentials

Condition	Distinguishing features
Pityriasis (tinea) versicolor	Hypopigmented (not chalk-white) scaly macules; KOH "spaghetti & meatballs"; Wood's lamp yellow-gold fluorescence
Pityriasis alba	Children, ill-defined hypopigmented fine-scaly patches on face; atopic background; self-limiting
Post-inflammatory hypopigmentation	History of preceding dermatosis; hypopigmented, not depigmented
Nevus depigmentosus	Congenital, stable, well-defined hypopigmented patch; no Wood's lamp accentuation, no leukotrichia
Idiopathic guttate hypomelanosis	Small, discrete, porcelain-white macules on sun-exposed shins/forearms, elderly
Tuberous sclerosis (ash-leaf macule)	Congenital hypomelanotic macules; other TS features (adenoma sebaceum, etc.)
Leprosy (tuberculoid/indeterminate)	Hypopigmented anaesthetic patch with sensory loss ± nerve thickening
Piebaldism	Congenital depigmentation with white forelock; stable; KIT mutation (vs acquired vitiligo)
Chemical leukoderma	Occupational exposure (phenols/catechols); confetti macules at contact sites

High-yield: Vitiligo = depigmented + acquired + Wood's lamp accentuation + may show leukotrichia/Koebner. Contrast with nevus depigmentosus/tuberous sclerosis (congenital, no accentuation) and leprosy (hypopigmented + anaesthetic).

Mnemonics and named facts

• Autoimmune associations — "THE DAMP": Thyroid (Hashimoto/Graves), Halo naevus, Endocrine (T1DM), Diabetes/Addison's, Alopecia areata, Megaloblastic (pernicious anaemia), Polyglandular syndromes.
• Wood's lamp colours: Vitiligo → bright blue-white; tinea versicolor → yellow-gold; erythrasma → coral-red; pseudomonas → green; porphyria urine → pink-red.
• Eponyms: Sutton's naevus (halo naevus), Koebner (isomorphic phenomenon), Vogt–Koyanagi–Harada and Alezzandrini syndromes, Jodhpur technique (non-cultured epidermal cell suspension).

Recently asked / exam angle

• Wood's lamp finding in vitiligo (bright blue-white, accentuated margins) vs other fluorescences — repeatedly asked image/match question.
• Segmental vs non-segmental differentiation: unilateral, dermatomal, stable, leukotrichia early, best surgical candidate.
• Most common autoimmune association = thyroid disease (screen TSH/anti-TPO).
• Phototherapy of choice = NB-UVB (311 nm), advantages over PUVA.
• Koebner phenomenon as a marker of activity (shared with psoriasis, lichen planus, warts).
• Topical ruxolitinib (JAK inhibitor) — newest FDA-approved agent; IFN-γ/CXCL10/JAK-STAT mechanism is a fresh, high-yield concept.
• Indication/contraindication for surgery (stability ≥6–12 months; active disease contraindicated).
• Depigmentation with monobenzone for extensive recalcitrant disease.
• Differentiating depigmentation vs hypopigmentation clinically (chalk-white vs off-white).
• Histology: absence of melanocytes (MART-1/Melan-A negative).

Rapid revision

1. Vitiligo = acquired autoimmune loss of melanocytes → chalk-white (depigmented) macules.
2. Wood's lamp = investigation of choice → bright blue-white accentuation, sharper margins.
3. Segmental = unilateral, dermatomal, stable, early leukotrichia, best for surgery, poor medical response.
4. Non-segmental = bilateral/symmetrical, strong thyroid association, Koebner positive, better medical response.
5. Most common autoimmune association = autoimmune thyroid disease → screen TSH + anti-TPO.
6. Koebner phenomenon, confetti macules, trichrome lesions = ACTIVE disease.
7. NB-UVB (311 nm) = phototherapy of choice; face/neck repigment best, acral & leukotrichia worst.
8. Topical steroids (body) and calcineurin inhibitors (face/folds) are first-line for limited disease.
9. Topical ruxolitinib (JAK inhibitor) — newest FDA-approved treatment; IFN-γ–CXCL10–CXCR3 axis.
10. Oral mini-pulse steroids to arrest rapidly spreading vitiligo.
11. Surgery (MKTP / epidermal grafting) only in stable disease ≥6–12 months; active disease is a contraindication.
12. Monobenzone (MBEH) depigments residual skin in extensive (>50%) recalcitrant disease — irreversible.