6.3 Pigmentary Disorders: Vitiligo, Melasma & Other Hypo- and Hyperpigmentation
Key Takeaways
- Vitiligo affects about 0.5% to 1% of people worldwide; non-segmental vitiligo is symmetric and autoimmune, while segmental vitiligo is unilateral, starts early, and stabilises quickly.
- Ruxolitinib 1.5% cream is approved in the EU for non-segmental vitiligo with facial involvement in patients aged 12 years and older.
- Stable segmental vitiligo that does not respond to medical treatment is the best indication for surgical grafting, such as melanocyte-keratinocyte transplantation.
- Melasma treatment rests on strict photoprotection, including tinted sunscreens against visible light, plus topical agents such as hydroquinone triple-combination cream or azelaic acid.
- Peutz-Jeghers syndrome, caused by STK11 mutations, combines lip and oral mucosal lentigines with gastrointestinal hamartomatous polyps and a raised cancer risk.
6.3 Pigmentary Disorders: Vitiligo, Melasma & Other Hypo- and Hyperpigmentation
Skin colour depends mainly on melanin, made by melanocytes in the basal layer and transferred in melanosomes to keratinocytes. Tyrosinase is the key enzyme. Eumelanin is brown-black, and pheomelanin is red-yellow; the balance depends partly on the MC1R receptor. Differences between skin types reflect melanosome size, number, and distribution, not melanocyte number.
A Wood lamp (UVA around 365 nm) helps separate epidermal from dermal pigment. Epidermal hyperpigmentation looks darker under Wood light, and depigmentation (vitiligo) shows as bright chalky white.
Vitiligo
Vitiligo is an acquired loss of melanocytes causing well-defined depigmented (milk-white) macules. Prevalence is about 0.5–1%.
Classification
| Type | Features | Course |
|---|---|---|
| Non-segmental (NSV) | Symmetric macules on the face (periorificial), hands, wrists, genitals, and bony sites; generalised, acrofacial, or universal forms; Koebner phenomenon | Chronic and unpredictable; linked to autoimmune thyroid disease and other autoimmunity |
| Segmental (SV) | Unilateral band-like patch, often starting in childhood; early leukotrichia (white hairs) | Spreads quickly then stabilises within about 1–2 years; responds poorly to medical therapy |
| Mixed | Segmental vitiligo followed by non-segmental lesions | — |
Pathogenesis of NSV: melanocyte stress and an autoimmune attack by CD8+ T cells, driven by interferon-gamma and the CXCL10/JAK-STAT pathway. This explains the effect of JAK inhibitors.
Signs of activity: confetti-like depigmentation, trichrome lesions (an intermediate zone of partial pigment loss), inflammatory borders, and Koebner phenomenon. Activity and extent can be tracked with tools such as the VASI (Vitiligo Area Scoring Index).
Work-up: thyroid function and thyroid antibodies, and other tests only if symptoms suggest them.
European Treatment Approach
| Goal | Options |
|---|---|
| Stop active spread | Oral mini-pulse corticosteroids (for example dexamethasone on 2 days a week) for rapidly progressing disease; phototherapy |
| Repigment limited disease | Topical corticosteroids (body) or topical calcineurin inhibitors (face, flexures); ruxolitinib 1.5% cream (EU-approved for non-segmental vitiligo with facial involvement from 12 years) |
| Repigment extensive disease | Narrowband UVB 2–3 times a week, often combined with topical agents; response is best on the face and poor on hands and feet |
| Stable, refractory patches | Surgery once disease is stable for at least about 12 months: punch grafts, suction blister grafts, or melanocyte-keratinocyte transplantation; best for segmental vitiligo |
| Extensive (over about 80%) refractory disease | Depigmentation of remaining pigment in selected patients |
| All patients | Sun protection, cosmetic camouflage, and psychological support |
Repigmentation usually starts perifollicularly, because the hair follicle holds a reservoir of melanocytes. Areas without hair (lips, fingertips) respond poorly.
Other Causes of Hypopigmentation
| Condition | Clues |
|---|---|
| Piebaldism | Congenital, stable, white forelock and ventral white patches; KIT mutation |
| Waardenburg syndrome | White forelock, heterochromia of the irises, deafness |
| Tuberous sclerosis | Ash-leaf macules, confetti macules (see genodermatoses) |
| Oculocutaneous albinism | Generalised hypopigmentation from birth, nystagmus, reduced vision; high skin cancer risk; OCA1 is caused by TYR mutations |
| Pityriasis versicolor | Fine scaly hypo- or hyperpigmented macules on the upper trunk; Malassezia; KOH shows "spaghetti and meatballs"; treat with ketoconazole shampoo or azoles |
| Pityriasis alba | Ill-defined pale scaly patches on the faces of atopic children |
| Idiopathic guttate hypomelanosis | Small porcelain-white macules on sun-exposed shins and forearms of older adults |
| Progressive macular hypomelanosis | Symmetrical pale macules on the trunk of young adults; red follicular fluorescence (Cutibacterium acnes) |
| Post-inflammatory hypopigmentation | After eczema, psoriasis, cryotherapy, or steroid injection |
| Leprosy and hypopigmented mycosis fungoides | Leprosy patches lose sensation; consider MF in darker-skinned young people with persistent patches |
| Naevus depigmentosus | Stable, congenital, well-defined off-white patch |
Hyperpigmentation
Melasma
- Who: mainly women with skin types III–V; triggered by UV and visible light, pregnancy (chloasma), hormonal contraception, and genetics.
- Clinical: symmetric light-to-dark brown patches on the forehead, cheeks, upper lip, and chin (centrofacial and malar patterns).
- Depth: epidermal, dermal, or mixed. Wood lamp and dermoscopy help, and dermal pigment responds less well.
- Treatment:
- Strict photoprotection with broad-spectrum sunscreen that also protects against visible light, using tinted products with iron oxides.
- Hydroquinone 2–4% (prescription-only in the EU; banned from cosmetics) or triple-combination cream (hydroquinone + tretinoin + fluocinolone acetonide) for limited periods.
- Azelaic acid, tranexamic acid (topical or oral, off-label; exclude thrombotic risk), and chemical peels.
- Lasers and intense pulsed light only with caution, because they can cause rebound pigmentation.
- Prolonged hydroquinone use can cause exogenous ochronosis (blue-black pigmentation).
Post-Inflammatory Hyperpigmentation (PIH)
PIH follows acne, eczema, lichen planus, trauma, or procedures, and is most marked in darker skin types. Treat the underlying inflammation early, protect from sun, and use azelaic acid, retinoids, or hydroquinone if needed.
Drug-Induced and Systemic Hyperpigmentation
| Cause | Pattern |
|---|---|
| Minocycline | Blue-black in scars (type I), on normal shins and forearms (type II), or diffuse muddy-brown on sun-exposed skin (type III) |
| Amiodarone | Slate-grey or violaceous pigmentation of sun-exposed skin; also photosensitivity |
| Antimalarials | Blue-grey pigmentation of the shins, face, hard palate, and nails |
| Chemotherapy | Bleomycin: flagellate streaks; 5-fluorouracil: serpentine pigmentation over veins |
| Clofazimine | Red-brown skin discolouration |
| Addison disease | Diffuse bronze pigment, darker in palmar creases, scars, and mucosa |
| Haemochromatosis | Bronze or grey skin with liver disease and diabetes |
| Argyria | Blue-grey skin after silver exposure |
Lentigines and Lentiginous Syndromes
- Solar lentigines: in chronically sun-exposed skin. PUVA lentigines follow photochemotherapy. Ephelides (freckles) darken in summer.
- Peutz-Jeghers syndrome (STK11): lentigines of the lips, buccal mucosa, fingers, and toes; hamartomatous GI polyps (intussusception, bleeding); increased GI, breast, pancreatic, and other cancer risk.
- Laugier-Hunziker syndrome: acquired oral and lip lentigines with longitudinal melanonychia, without systemic disease.
- Noonan syndrome with multiple lentigines (formerly LEOPARD, PTPN11) and Carney complex (PRKAR1A: lentigines, cardiac myxomas, endocrine tumours).
- Café-au-lait macules: six or more (over 5 mm before puberty, over 15 mm after) suggest NF1.
- Becker naevus: a unilateral brown patch with increased hair on the shoulder of adolescent boys.
Dermal Melanocytosis
- Congenital dermal melanocytosis ("Mongolian spot"): blue-grey patches over the sacrum in infants with darker skin; fades in childhood.
- Naevus of Ota: blue-grey pigment in the first and second divisions of the trigeminal nerve, with ocular melanocytosis. It carries a risk of glaucoma and, rarely, melanoma of the eye or skin. Q-switched or picosecond lasers are effective.
- Naevus of Ito: the same over the shoulder (supraclavicular and lateral brachial nerves).
A 15-year-old girl has a single band-like depigmented patch on the left side of her face and neck with white eyelashes. It spread quickly 2 years ago and has not changed for 18 months despite topical tacrolimus and phototherapy. What is the most appropriate next option?
A 25-year-old woman with non-segmental vitiligo on her face and hands asks about new topical treatments. Which topical agent is approved in the EU for non-segmental vitiligo with facial involvement from 12 years of age?
A 34-year-old woman with skin type IV has symmetric brown patches on her cheeks, forehead, and upper lip that started during pregnancy and darken in summer. Which treatment plan is most appropriate?
A 20-year-old man has multiple small brown macules on his lips and buccal mucosa and recurrent abdominal pain; endoscopy shows hamartomatous polyps. Which gene is most likely mutated?