Overview
Vitiligo
1. Overview
Vitiligo is an acquired, chronic pigmentary disorder characterized by the autoimmune destruction of melanocytes, resulting in well-defined chalk-white macules and patches on the skin and mucous membranes. It affects approximately 0.5-2% of the global population and can cause significant psychological morbidity.
Key Features
- Pathology: Loss of functional melanocytes in the epidermis
- Distribution: Often symmetrical and periorificial (Non-segmental) or unilateral/dermatomal (Segmental)
- Koebner Phenomenon: Development of lesions at sites of trauma (e.g., friction, cuts)
- Course: Unpredictable; spontaneous repigmentation can occur but complete self-resolution is rare
Epidemiology
| Factor | Details |
|---|---|
| Prevalence | 0.5-2% worldwide |
| Onset | 50% start before age 20 |
| Gender | Equal incidence |
| Genetics | Polygenic; 20% have a positive family history |
Classification
-
Non-Segmental Vitiligo (NSV):
- Most common (90%)
- Bilateral, symmetrical
- Progressive course
- Includes: Generalized, Acrofacial, Mucosal, Universal
-
Segmental Vitiligo (SV):
- Unilateral, dermatomal distribution
- Rapid onset then stabilizes
- Less associated with autoimmune diseases
- Poor response to medical therapy (often requires surgery)
2. Pathophysiology
┌─────────────────────────────────────────────────────────────────────────────┐
│ VITILIGO PATHOPHYSIOLOGY │
├─────────────────────────────────────────────────────────────────────────────┤
│ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ GENETIC SUSCEPTIBILITY + ENVIRONMENTAL TRIGGER │ │
│ │ • Susceptibility Genes: NLRP1, TYR, HLA-A2, HLA-DR4 │ │
│ │ • Triggers: Stress, trauma (Koebner), phenols, viral infection │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ OXIDATIVE STRESS IN MELANOCYTES │ │
│ │ • Defective antioxidant mechanisms │ │
│ │ • Accumulation of Reactive Oxygen Species (ROS) │ │
│ │ • Melanocytes become fragile and stressed │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ AUTOIMMUNE ACTIVATION (T-CELL MEDIATED) │ │
│ │ • Stressed melanocytes release DAMPs (e.g., HSP70) │ │
│ │ • Activation of Innate Immunity → IFN-γ release │ │
│ │ • CD8+ Cytotoxic T-Cells recruited via CXCL10 chemokine │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ MELANOCYTE DESTRUCTION │ │
│ │ • CD8+ T-cells target melanocyte antigens (Tyrosinase, MART-1) │ │
│ │ • Apoptosis and detachment of melanocytes (Melanocytorrhagy) │ │
│ │ • Loss of pigment production │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌──────────────────────┬──────────────────────────────────────┐ │
│ ↓ ↓ │ │
│ ┌─────────┐ ┌─────────────┐ │ │
│ │ DEPIG-│ │ MEMORY T- │ │ │
│ │ MENTED │ │ CELLS │ │ │
│ │ MACULES │ │ (Recurrence)│ │ │
│ └─────────┘ └─────────────┘ │ │
│ │ │
└─────────────────────────────────────────────────────────────────────────────┘
The JAK-STAT Pathway Role
- Interferon-gamma (IFN-γ) is the central driver of vitiligo pathogenesis.
- IFN-γ signaling leads to production of chemokines CXCL9 and CXCL10.
- These chemokines recruit autoreactive CD8+ T-cells to the skin.
- The JAK-STAT pathway (specifically JAK1/2) is crucial for this signaling.
- Therapeutic implication: JAK inhibitors (e.g., Ruxolitinib) block this pathway, halting depigmentation and allowing repigmentation.
Autoimmune Associations
Vitiligo share genetic risk factors with other autoimmune diseases. Always screen for:
- Thyroid Disease (Hashimoto's thyroiditis, Graves disease) - up to 20-30%
- Type 1 Diabetes
- Pernicious Anemia
- Addison's Disease
- Alopecia Areata
3. Clinical Features
History Taking
Key Questions:
- Age of onset?
- Distribution (Symmetrical vs Unilateral)?
- Rate of progression? (Stable vs Active)
- Preceding trauma or sunburn?
- Family history of vitiligo or autoimmune disease?
- Impact on quality of life?
Physical Examination
Morphology:
- Chalk-white macules: Well-demarcated, completely depigmented
- Trichrome vitiligo: Three zones of color (normal, hypopigmented, depigmented) - sign of activity
- Poliosis: White hair within patches (implies destruction of follicle melanocytes - harder to treat)
Common Sites:
- Face: Periorificial (around eyes, mouth) - "Acrofacial"
- Extremities: Hands (fingers, wrists), feet, elbows, knees
- Genitalia: Common site
Signs of Disease Activity:
- Ill-defined borders ("confetti-like" depigmentation)
- Koebner phenomenon (linear lesions at trauma sites)
- Trichrome vitiligo
4. Diagnosis
Diagnostic Approach
Vitiligo is primarily a clinical diagnosis. Biopsy is rarely needed.
Wood's Lamp Examination
Essential tool for assessment, especially in fair-skinned individuals.
- Finding: Lesions fluoresce a bright, chalky-white color.
- Utility:
- Distinguishes from other hypopigmented disorders (e.g., Pityriasis alba, Tinea versicolor)
- Reveals subclinical extent of disease not visible to naked eye
Laboratory Investigations
Routine bloods to screen for associated autoimmune conditions:
- TSH and TPO Antibodies (Thyroid screen - Mandatory)
- FBC (Pernicious anemia)
- HbA1c (Diabetes - if symptoms suggest)
- ANA (Only if connective tissue disease symptoms)
Differential Diagnosis
| Condition | Key Differentiators |
|---|---|
| Pityriasis Versicolor | Fungal infection, scaling, KOH positive, yellow-green fluorescence |
| Pityriasis Alba | Ill-defined, scaly, common on cheeks in children (atopic) |
| Post-inflammatory hypopigmentation | History of prior inflammation (eczema, psoriasis), not chalk-white |
| Chemical Leukoderma | History of exposure to phenols/catechols |
| Piebaldism | Congenital, stable, white forelock |
| Leprosy | Hypopigmented (not depigmented), anesthetic patches |
5. Management Algorithm
┌─────────────────────────────────────────────────────────────────────────────┐
│ VITILIGO MANAGEMENT ALGORITHM │
├─────────────────────────────────────────────────────────────────────────────┤
│ │
│ DIAGNOSIS CONFIRMED │
│ ↓ │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ GENERAL MEASURES (ALL PATIENTS) │ │
│ │ • Sun protection (prevents burn of white skin & contrast) │ │
│ │ • Camouflage/Cosmetic cover (Dermablend, Microskin) │ │
│ │ • Psychological support │ │
│ │ • Screen for Thyroid Disease (TSH, TPO) │ │
│ │ • Assess Quality of Life (DLQI) │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ ↓ │
│ ┌──────────────────────────────────────┐ │
│ │ EXTENT OF DISEASE? │ │
│ └──────────────────────────────────────┘ │
│ ↓ Limited (<10-20% BSA) ↓ Extensive (>20% BSA) │
│ ┌──────────────────────────┐ ┌──────────────────────────────────────┐ │
│ │ TOPICAL THERAPY │ │ SYSTEMIC / LIGHT THERAPY │ │
│ │ (First Line) │ │ (First Line) │ │
│ │ │ │ │ │
│ │ Option A: Potent TCS │ │ Option A: NB-UVB Phototherapy │ │
│ │ (e.g., Mometasone, │ │ • 2-3 sessions/week │ │
│ │ Clobetasol) │ │ • Continue if re-pigmenting │ │
│ │ - Face: pulse use only │ │ • Max benefit at 6-12 months │ │
│ │ │ │ │ │
│ │ Option B: TCIs │ │ Option B: Systemic Steroids │ │
│ │ (Tacrolimus 0.1% oint) │ │ (Mini-pulse therapy) │ │
│ │ - Best for FACE/NECK │ │ • For RAPIDLY PROGRESSIVE disease │ │
│ │ - Safe long term │ │ • E.g., Dexamethasone 2.5mg │ │
│ │ │ │ on Sat/Sun only │ │
│ │ Option C: JAK Inhibitor │ │ │ │
│ │ (Ruxolitinib 1.5% cream)│ │ │ │
│ │ - Highly effective │ │ │ │
│ │ - Expensive │ │ │ │
│ └──────────────────────────┘ └──────────────────────────────────────┘ │
│ ↓ No response after 3-6m ↓ No response │
│ ┌─────────────────────────────────────────────────────────────────────┐ │
│ │ COMBINATION THERAPY OR SURGERY │ │
│ │ • Combine Light Therapy + Topicals │ │
│ │ • Oral JAK Inhibitors (Emerging treatment) │ │
│ │ • SURGERY (For Stable Segmental Vitiligo only) │ │
│ │ - Suction Blister Grafting │ │
│ │ - Melanocyte-Keratinocyte Transplant (MKTP) │ │
│ └─────────────────────────────────────────────────────────────────────┘ │
│ │
└─────────────────────────────────────────────────────────────────────────────┘
Topical Therapies (Limited Disease)
-
Topical Corticosteroids (TCS):
- Body: Potent/Super-potent (e.g., Clobetasol) for 3-4 months.
- Face/Intertriginous: Avoid continuous use due to atrophy risk.
- Efficacy: Best on face/neck, poorest on hands/feet.
-
Topical Calcineurin Inhibitors (TCI):
- Agents: Tacrolimus 0.1% ointment, Pimecrolimus cream.
- Indication: First-line for FACE and NECK.
- Benefit: No steroid atrophy risk. Safe for long-term use.
-
Topical JAK Inhibitors:
- Ruxolitinib 1.5% cream: First FDA-approved repigmentation agent.
- Mechanism: Blocks IFN-γ signaling.
- Efficacy: High rates of facial repigmentation (~30-50% at 24 weeks).
Phototherapy (Extensive Disease)
Narrowband UVB (NB-UVB):
- Gold standard for extensive (>10-20% BSA) vitiligo.
- Mechanism: Stimulates melanocyte migration from hair follicle reservoir and suppresses autoimmune T-cells.
- Regimen: 2-3 times per week. Minimum 3 months trial.
- Limitations: Hair follicles must be pigmented (poliosis predicts poor response). Hands/feet respond poorly.
Surgical Management
Indications:
- Stable disease (no new lesions or expansion >1 year)
- Segmental vitiligo (often first-line after stabilization)
- Refractory to medical therapy
Techniques:
- Tissue Grafting: Suction blister grafting, punch grafting.
- Cellular Grafting: Non-cultured Epidermal Cell Suspension (NCES/MKTP) - best for larger areas.
6. Depigmentation Therapy
Reserved for patients with extensive vitiligo (>50-80% BSA) who fail repigmentation or prefer uniform color.
- Agent: Monobenzyl ether of hydroquinone (Monobenzone).
- Mechanism: Induces permanent destruction of remaining melanocytes.
- Result: Complete, permanent depigmentation (chalk white).
- Consideration: Irreversible. Requires lifelong sun protection.
7. Prognosis
Predictors of Response
| Feature | Favorable Response | Poor Response |
|---|---|---|
| Site | Face, Neck, Trunk | Hands, Feet, Lips, Genitals |
| Duration | Recent onset | Long-standing |
| Hair | Pigmented hair present | Poliosis (white hair) |
| Type | Non-segmental | Segmental (to medical Rx) |
| Koebner | Absent | Present |
Natural History
- Usually progressive with periods of stability.
- Spontaneous repigmentation occurs in 10-20% (usually sun-exposed areas) but is rarely cosmetic.
- Segmental vitiligo progresses rapidly for 6-12 months then stabilizes for life.
8. Complications
Physical
- Sunburn: Depigmented skin has no natural protection.
- Eye abnormalities: Iritis/uveitis (melanocytes in uveal tract may be affected) - rare.
- Hearing loss: Sensorineural (melanocytes in cochlea) - rare/subclinical.
Psychosocial
- High impact: Low self-esteem, depression, social anxiety.
- Stigma: Especially in cultures where it may be confused with leprosy.
- Quality of Life: Comparable impairment to psoriasis or eczema.
9. Special Considerations
Children
- Avoid potent steroids on face/body for long periods.
- Tacrolimus 0.03% or 0.1% preferred for long-term safety.
- NB-UVB safe for older children.
- High rate of spontaneous repigmentation compared to adults.
Segmental Vitiligo
- Distinct behavior: Rapid onset, unilateral, stabilizes early.
- Poorly responsive to medical therapy (topicals/UVB).
- Treatment of choice: Surgical grafting once stable.
10. Key Clinical Pearls
Exam-Focused Points
- Koebner Phenomenon: Lesions appearing at trauma sites (belt line, watch strap). Sign of activity.
- Poliosis: White hair within a patch indicates loss of the melanocyte reservoir (the hair follicle). Predicts poor response to medical therapy (UVB works by stimulating specific follicle melanocytes).
- Face vs Hands: Face responds bestities (high follicle density); Hands/Feet respond poorly (acral skin, few follicles).
- Thyroid Screen: Always check TSH/TPO in vitiligo patients.
- Wood's Lamp: Essential for diagnosis in light skin types.
- JAK Inhibitors: The new "wonder drug" class for vitiligo (Ruxolitinib).
- Steroid Sparing: Use Tacrolimus for the face to avoid atrophy/glaucoma.
Common Exam Scenarios
- Patient with white patches around eyes and mouth: Diagnosis? (Vitiligo). Management? (Tacrolimus).
- Patient with rapidly spreading white patches: Management? (Oral mini-pulse steroids to halt progression).
- Unilateral band of white skin in a child: Diagnosis? (Segmental Vitiligo). Prognosis? (Will stabilize, unlikely to spread elsewhere).
11. Patient Explanation
What is Vitiligo?
"Vitiligo is an autoimmune condition where your body's immune system sets off a false alarm and attacks its own pigment cells (melanocytes). These are the cells that give your skin its color. When they are destroyed, the skin turns chalk-white."
Is it Contagious?
"No. Vitiligo is absolutely not contagious. You cannot catch it from someone or give it to someone. It is not an infection."
Can it be Cured?
"While there is no permanent 'cure' that guarantees it will never come back, we have very effective treatments to restore color:
- Creams: Steroid creams or non-steroid alternatives can suppress the immune attack.
- Light Therapy: Narrowband UVB uses light to wake up sleeping pigment cells in your hair follicles.
- New Treatments: JAK inhibitors are new creams that target the specific immune pathway involved."
What Can I Do?
"1. Sun Protection: The white patches have no natural protection and burn easily. Burning can actually make vitiligo worse (Koebner phenomenon). 2. Reduce Trauma: Avoid tight clothes or rubbing, as damage to skin can trigger new patches. 3. Patience: Repigmentation takes time - usually 3 to 6 months to see significant results."
12. Evidence & Guidelines
Key Guidelines
| Guideline | Organization | Year | Key Points |
|---|---|---|---|
| Vitiligo Guidelines | British Association of Dermatologists (BAD) | 2021 | NB-UVB recommendations, topical safety |
| European Guidelines | EADV | 2013 | Definition, assessment, therapeutic algorithm |
| Global Consensus | VGICC | 2012 | Classification of vitiligo (Segmental vs Non-segmental) |
Landmark Trials
TRuE-V1 and TRuE-V2 Trials (2022):
- Investigated Ruxolitinib cream (JAK inhibitor).
- Significant repigmentation of face (approx 30%) and body vs vehicle.
- Led to FDA approval.
NB-UVB vs PUVA studies:
- Established Narrowband UVB as superior to PUVA (Psoralen + UVA) for efficacy and safety.
Evidence-Based Recommendations
| Recommendation | Evidence Level |
|---|---|
| Topical steroids for limited disease | High |
| Topical calcineurin inhibitors for face | High |
| NB-UVB for extensive disease | High |
| Ruxolitinib cream | High (TRuE-V trials) |
| Oral antioxidants (e.g., Gingko) | Low/Weak |
13. References
-
Eleftheriadou V, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021. Br J Dermatol. 2022;186(1):18-29.
-
Rosmarin D, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022;387(16):1445-1455.
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Taieb A, et al. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013;168(1):5-19.
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Ezzedine K, et al. Vitiligo. Lancet. 2015;386(9988):74-84.
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Whitton ME, et al. Interventions for vitiligo. Cochrane Database Syst Rev. 2015;(2):CD003263.
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Ezzedine K, et al. Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference. Pigment Cell Melanoma Res. 2012;25(3):E1-13.