How are pigmentary disorders classified?
Skin colour comes from melanin made by melanocytes — neural-crest-derived cells that make up about 5–10% of cells in the epidermal basal layer (see layers of the epidermis). Melanin is synthesised inside melanosomes; the first, rate-limiting step is the oxidation of tyrosine to DOPA by tyrosinase. Pigmentary disorders are best sorted by asking two questions: is pigment lost or increased, and are melanocytes absent or merely malfunctioning?
| Disorder | Pigment | Melanocytes | Core defect |
|---|---|---|---|
| Vitiligo | Lost (depigmented, milk-white) | Absent in lesions | Autoimmune CD8+ T-cell destruction of melanocytes |
| Piebaldism | Lost (white patches) | Absent in patches | Melanocytes missing from affected skin |
| Albinism | Reduced or absent everywhere | Normal number | Genetic defect in melanin synthesis or melanosome function |
| Melasma | Increased (brown to grey) | Not markedly increased; hyperactive | Excess melanogenesis from light and hormones, with dermal changes |
What causes vitiligo and how does it present?
Vitiligo is the most common acquired depigmenting disorder, affecting about 0.5–2% of people worldwide with no clear sex or racial predilection. Most patients develop it before age 30. It is now regarded as a T-cell-mediated autoimmune disease: autoreactive CD8+ cytotoxic T cells release interferon-gamma, which activates the JAK-STAT pathway in keratinocytes; these release CXCL9 and CXCL10, recruiting more T cells. Tissue-resident memory T cells explain relapse at the same sites — and JAK signalling explains why JAK inhibitors now treat it.
- Lesions: asymptomatic, well-demarcated, milky or chalk-white macules and patches, level with the skin, without scale.
- Sites: periorificial (eyes, mouth, anogenital), acral (hands, fingers, feet) and friction-prone extensor surfaces (elbows, knees, ankles).
- Koebner (isomorphic) phenomenon: new patches at sites of trauma or friction, in about 20–60% — a sign of active disease.
- Leukotrichia (poliosis): white hair within a patch means the follicular melanocyte reservoir is destroyed — a poor prognostic sign for medical repigmentation.
- Trichrome vitiligo: three shades — white patch, an intermediate hypopigmented zone and normal skin. Confetti-like depigmentation and ill-defined borders also signal activity.
- Associations: autoimmune thyroid disease (most common), alopecia areata, pernicious anaemia, type 1 diabetes, halo naevi.
What are the types of vitiligo?
| Feature | Non-segmental vitiligo | Segmental vitiligo |
|---|---|---|
| Frequency | Most common — about 85–90% | Less common (15–30% of childhood cases) |
| Distribution | Bilateral, often symmetrical | Unilateral, dermatomal or along Blaschko's lines |
| Subtypes | Generalised (vulgaris), acrofacial, mucosal, universal (more than 80–90% of body surface) | Uni-, bi- or multi-segmental |
| Onset and course | Any age; chronic, unpredictable, with flares | Early onset, rapid spread, then stabilises within 1–2 years |
| Leukotrichia | Less frequent | Frequent |
| Autoimmune association | Stronger | Weaker |
| Best surgical candidates | Stable patches | Cellular grafting works especially well |
Age of onset differs too: DermNet reports that about 41% of segmental cases start before age 10, and about 50% of non-segmental cases before age 20. A patient can occasionally have both patterns (mixed vitiligo), usually with segmental disease first.
How is vitiligo diagnosed — and what does the Wood's lamp show?
Diagnosis is clinical. A Wood's lamp emits long-wave ultraviolet A at about 365 nm. Depigmented vitiligo skin shows bright blue-white fluorescence with a sharp edge, which helps detect early or subclinical patches in fair skin (Fitzpatrick I–III), map the true extent and spot micro-Koebnerisation. A biopsy is rarely needed; it shows complete absence of melanocytes (confirmed with Fontana–Masson for melanin and Melan-A, HMB-45 or SOX10 for melanocytes).
| Condition | Key clue |
|---|---|
| Nevus depigmentosus | Congenital or early, stable, grows with the body; Wood's lamp shows off-white accentuation, not bright blue-white |
| Ash-leaf macules | Hypopigmented (not depigmented) lanceolate macules from infancy with tuberous sclerosis features |
| Pityriasis alba | Ill-defined, finely scaly patches on a child's face — a mild form of atopic dermatitis |
| Pityriasis (tinea) versicolor | Scaly trunk macules, yellow-green Wood's fluorescence, positive KOH |
| Progressive macular hypomelanosis | Trunk patches with punctate red follicular fluorescence (Cutibacterium acnes) |
| Idiopathic guttate hypomelanosis | Small pearly-white macules on sun-exposed skin of older adults |
| Chemical leukoderma | Exposure to phenolic compounds or certain drugs |
| Hypopigmented mycosis fungoides | Subtle scale or atrophy; biopsy needed |
How is vitiligo treated?
Treatment aims to halt progression and induce repigmentation, and is chosen by disease activity, extent and site.
| Situation | Treatment |
|---|---|
| Localised disease (under 10% body surface area) | Topical corticosteroids first-line on trunk and limbs; tacrolimus 0.1% preferred on the face and skin folds; calcipotriol as an adjunct; topical ruxolitinib 1.5% (JAK inhibitor), especially for facial vitiligo |
| Active, rapidly spreading disease | Oral mini-pulse corticosteroids for rapid stabilisation; azathioprine, methotrexate or ciclosporin as steroid-sparing options |
| Generalised disease | Narrowband UVB (311 nm) — the mainstay; safe long term, including in children and pregnancy |
| Localised resistant patches | 308-nm excimer laser or lamp, especially face and neck |
| Refractory or extensive | Oral JAK inhibitors (tofacitinib, baricitinib, upadacitinib, ritlecitinib) |
| Stable disease (6–12 months) failing medical therapy | Surgery: suction blister or punch grafts; non-cultured epidermal cell suspension; melanocyte–keratinocyte transplantation |
| Extensive disease (more than 80% body surface) | Depigmentation of remaining normal skin with monobenzone 20% |
What is melasma and how is it treated?
Melasma (formerly chloasma, the 'mask of pregnancy') is a common, chronic, relapsing acquired hyperpigmentation: symmetrical, irregularly bordered brown to grey-brown macules and patches on sun-exposed facial skin. It mainly affects women of reproductive age and darker skin types (Fitzpatrick III–V) and is uncommon before puberty.
- Triggers: chronic ultraviolet and visible-light exposure (the most consistent, modifiable trigger), hormones — pregnancy, oral contraceptives, hormone replacement — and genetic predisposition. DermNet links hormones to about one-quarter of affected women.
- Facial patterns: centrofacial (forehead, cheeks, nose, upper lip sparing the philtrum — the commonest, 50–80%), malar (cheeks and nose) and mandibular (jawline and chin). Extrafacial melasma occurs on forearms and neck, more often after menopause.
- Depth: traditionally epidermal (pigment accentuates under Wood's lamp), dermal (no accentuation) or mixed. StatPearls notes Wood's lamp findings are inconsistent, especially in darker skin, so this is now a pragmatic rather than strict classification; dermoscopy is preferred.
- Histology: more melanin in basal and suprabasal keratinocytes without a marked rise in melanocyte number, plus dermal changes of photoageing — solar elastosis, basement-membrane damage and increased vascularity.
| Step | Measures |
|---|---|
| Photoprotection (all patients, indefinitely) | Daily broad-spectrum sunscreen; tinted sunscreens with iron oxides to block visible light |
| Induction (first-line) | Hydroquinone-based regimens, often the triple-combination cream: fluocinolone acetonide 0.01% + hydroquinone 4% + tretinoin 0.05%, for limited courses |
| Maintenance / alternatives | Azelaic acid, cysteamine, kojic acid, topical retinoids; avoid irritation |
| Moderate–severe or refractory | Oral tranexamic acid as an adjunct after screening for thrombosis risk, pregnancy and oestrogen-containing contraception |
| Adjuncts | Superficial glycolic acid peels; lasers only for selected refractory cases because of rebound and post-inflammatory hyperpigmentation |
What is albinism and what are its types?
Albinism is a group of inherited conditions with reduced or absent melanin in skin, hair and eyes. Its overall occurrence is about 1 in 17,000 to 20,000. Melanocytes are present in normal numbers; the problem is melanin synthesis or melanosome function.
| Type | Gene / inheritance | Key features |
|---|---|---|
| OCA1 (OCA1A, OCA1B) | TYR (tyrosinase), autosomal recessive | OCA1A: complete absence of melanin — white skin and hair, light or pink irides, severe visual loss |
| OCA2 | OCA2 gene (P protein), autosomal recessive | Most common type worldwide; frequent in sub-Saharan Africa; creamy skin, yellow to light-brown hair |
| OCA3–OCA7 | TYRP1, SLC45A2, SLC24A5, LRMDA etc.; all autosomal recessive | Variable residual pigment |
| Ocular albinism (OA1) | GPR143, X-linked | Eye findings with near-normal skin; macromelanosomes |
| Hermansky–Pudlak syndrome | HPS genes, autosomal recessive | Albinism + bleeding diathesis (absent platelet dense granules), ceroid deposits; some forms get pulmonary fibrosis and granulomatous colitis |
| Chediak–Higashi syndrome | LYST, autosomal recessive | Albinism + giant lysosomal granules, recurrent pyogenic infections, neutropenia, neuropathy |
- Eye findings: foveal hypoplasia, infantile nystagmus (usually by 4 months), iris transillumination, photophobia, reduced acuity, and strabismus because too many optic-nerve fibres cross at the chiasm (misrouting).
- Skin: sunburn, solar lentigines, actinic keratoses and UV-related cancers — especially squamous cell carcinoma.
- Management: lifelong sun protection (SPF 30 or higher, reapplied every 2 hours, protective clothing and eyewear), regular skin checks, optical correction, and genetic counselling.
