Vitiligo

Vitiligo is an acquired autoimmune depigmenting disorder caused by selective destruction of epidermal melanocytes, producing well-demarcated white macules and patches. It affects 0.5 to 2% of the population worldwide with no sex predilection. About half of cases begin before age 20, and the peak onset is 10 to 30 years.

Pathogenesis

• CD8+ cytotoxic T cells target melanocytes through an interferon gamma, CXCL9 and CXCL10 axis driven by JAK1/JAK2 signalling.
• Oxidative stress, melanocyte-intrinsic defects, genetic susceptibility (over 50 loci including NLRP1, PTPN22, HLA class I and II, FOXP3, CTLA4) and innate immune activation contribute.
• Koebner phenomenon at sites of trauma reflects local immune priming.
• Concordance in monozygotic twins is only about 23%, so environment matters. Chemical leukoderma from phenols and catechols is a recognised trigger.

Classification

• Non-segmental (generalised) vitiligo: the commonest. Includes acrofacial, mucosal, universal (over 80% depigmentation) and mixed forms. Bilateral and symmetric, progressive and relapsing.
• Segmental vitiligo: unilateral, dermatomal or quasi-dermatomal. Early onset, rapid initial spread then stability, with leukotrichia early. Poor autoimmune association.
• Undetermined or unclassified: focal (single patch) or mucosal only.
• Associations: autoimmune thyroid disease (Hashimoto and Graves, in 15 to 25%), type 1 diabetes, alopecia areata, pernicious anaemia, Addison disease, rheumatoid arthritis, psoriasis, systemic lupus, inflammatory bowel disease, and autoimmune polyglandular syndromes. Ocular findings (uveitis, retinal pigment changes) and mild hearing loss occur occasionally. Psychosocial burden is substantial, with depression, anxiety, social avoidance and reduced quality of life, especially with facial and hand disease and in darker skin.
• Disease activity markers: confetti-like depigmentation, trichrome lesions, inflammatory borders, Koebner phenomenon, and spread within 3 to 6 months. Stable disease is no new lesions or extension for 6 to 12 months.

Lesions

• Milk-white, chalky, sharply demarcated, asymptomatic macules and patches with convex borders, usually non-scaly. Mild itch precedes lesions in a minority.
• Distribution: face (periorificial around mouth and eyes), dorsal hands and fingers, wrists, elbows, knees, ankles, axillae, groin, genitals and nipples. Bony prominences and areas of friction are typical.
• Hair in lesions turns white (leukotrichia), indicating loss of follicular melanocyte reservoir and a lower response to repigmentation.
• Trichrome vitiligo (tan intermediate zone), quadrichrome, blue vitiligo (post-inflammatory), inflammatory vitiligo with erythematous raised border, and punctate (confetti) forms.
• Segmental disease: unilateral band, often on the face (trigeminal distribution) or trunk.
• Mucosal involvement of the lips, glans penis and vulva is frequent in generalised disease.
• Wood lamp (365 nm) examination accentuates depigmentation, particularly in fair skin, with chalk-white fluorescence. Dermoscopy shows perifollicular pigment retention and residual pigment.

Differential diagnosis

• Pityriasis alba, post-inflammatory hypopigmentation, tinea versicolor, nevus depigmentosus and nevus anaemicus (stable from birth), piebaldism (congenital, midline), idiopathic guttate hypomelanosis, chemical or drug-induced leukoderma, lichen sclerosus, hypopigmented mycosis fungoides, leprosy (anaesthetic hypopigmented patches), tuberous sclerosis (ash-leaf macules), albinism, Vogt-Koyanagi-Harada disease, and melanoma-associated leukoderma.
• Red flags: rapid progression, personal or family autoimmune disease, hypopigmented patches with scale or atrophy, sensory loss (leprosy), and depigmentation after melanoma treatment or immunotherapy (a favourable prognostic sign in melanoma).

Diagnosis is clinical, supported by Wood lamp examination. Biopsy is reserved for atypical presentations: histology shows absent melanocytes (confirmed with Melan-A or SOX10 staining), sparse lymphocytic infiltrate at the border in active disease.

Baseline assessment

• Vitiligo Area Scoring Index (VASI) and Vitiligo Extent Score (VES) for extent, plus Vitiligo Disease Activity (VIDA) score. Photographic documentation under standard lighting.
• TSH, free T4 and anti-thyroid peroxidase antibodies (repeat every 1 to 2 years), fasting glucose or HbA1c, CBC, vitamin B12.
• Consider morning cortisol, ANA, coeliac serology and other autoimmune screens when symptoms suggest.
• Ophthalmological and audiological review if visual or hearing symptoms.
• Screen for depression and anxiety (PHQ-9, GAD-7) and use the Dermatology Life Quality Index.
• Fungal scraping (KOH), VDRL, or skin slit smear when mimics are suspected.

Aims: arrest progression, induce repigmentation, and support psychological wellbeing. Repigmentation comes from the follicular melanocyte reservoir (perifollicular pattern), so face and neck respond best, while acral and mucosal areas respond poorly. Treatment should run for at least 3 to 6 months before judging response.

General measures

• Broad-spectrum sunscreen SPF 30 to 50 daily, to prevent sunburn and Koebnerisation and reduce contrast. Avoid skin trauma, tattoos, friction and phenolic chemicals.
• Camouflage (cosmetic cover, dihydroxyacetone self-tanners), psychological support, counselling and peer groups.

Limited disease (under 5 to 10% body surface area, or stable)

• Topical corticosteroids: clobetasol propionate 0.05% or mometasone furoate 0.1% once daily for 2 months, then a break of 2 weeks, repeated. Use class III to IV on face and flexures for shorter periods. Monitor for atrophy, telangiectasia and striae.
• Topical calcineurin inhibitors: tacrolimus 0.1% ointment twice daily, pimecrolimus 1% cream twice daily, for 6 months or more. Preferred on the face, neck and genitals. Combine with sun exposure or phototherapy for synergy.
• Topical ruxolitinib 1.5% cream twice daily, a JAK1/2 inhibitor approved for non-segmental vitiligo. About 30 to 50% reach 75% facial repigmentation at 24 to 52 weeks. Limit to 10% body surface area, and monitor for acne, application-site reactions and rare systemic JAK effects.
• Topical vitamin D analogues (calcipotriol 0.005%) are weak as monotherapy and are used as adjuncts.
• Targeted phototherapy: 308 nm excimer laser or lamp, 2 to 3 times weekly, for focal disease (best on face, 50 to 70% repigmentation at 3 to 6 months).

Extensive or progressive disease (over 10% body surface area or active)

• Narrowband UVB (311 nm) phototherapy 2 to 3 times weekly, starting at 200 mJ/cm2 (or 70% of minimal erythema dose) and increasing by 10 to 20% per session, for 6 to 12 months or longer. Face and neck respond best (greater than 75% repigmentation in 40 to 60%). Combine with topical tacrolimus or ruxolitinib to improve results.
• Oral mini-pulse corticosteroids for rapidly progressive disease: dexamethasone 2.5 to 5 mg on two consecutive days weekly, or prednisolone 0.3 mg/kg daily for 3 to 4 months, with tapering, to arrest activity. Weigh adverse effects.
• Oral JAK inhibitors are used off-label for active extensive disease with phototherapy (tofacitinib 5 mg twice daily, baricitinib 2 to 4 mg daily, upadacitinib 15 mg daily), with baseline lipid, CBC, liver tests, tuberculosis and hepatitis screening and monitoring for infection, thrombosis and cardiovascular risk. Relapse occurs after stopping.
• Antioxidants (vitamin E, alpha-lipoic acid, Polypodium leucotomos 240 mg twice daily) are adjuncts of unproven benefit. Methotrexate 10 to 15 mg weekly and azathioprine have limited data.

Surgical repigmentation (stable disease for at least 6 to 12 months, no Koebner phenomenon, segmental or focal disease)

Autologous non-cultured epidermal cell suspension, suction blister grafting, punch grafting, split-thickness grafting, and hair follicle transplantation. Repigmentation rates 70 to 90% in segmental disease. Cobblestoning, scarring and mismatch are risks. Perform a test graft first.

Depigmentation for universal vitiligo (over 50 to 80% involvement, refractory)

Monobenzone 20% cream (monobenzyl ether of hydroquinone) twice daily for 9 to 12 months, or 4-methoxyphenol with Q-switched laser. Irreversible, with permanent sun sensitivity, so counselling and informed consent are essential.

Special populations

• Children: topical corticosteroids (mid potency, short courses) and calcineurin inhibitors, excimer light. Avoid oral steroids and systemic JAK inhibitors where possible.
• Pregnancy: avoid JAK inhibitors, psoralens, and methotrexate. NB-UVB is acceptable. Topical calcineurin inhibitors are generally used with caution.

Follow-up

Review every 3 months to document response and adherence. Annual thyroid testing. Treat comorbid autoimmune disease. Provide sun protection counselling and mental health support. Stabilisation can occur spontaneously, and relapse after treatment is common (about 40%), so maintenance twice weekly topical therapy to repigmented areas lowers recurrence.