Disorders of Pigmentation

• Vitiligo — acquired, autoimmune destruction of melanocytes, giving sharply demarcated, completely depigmented (chalk-white) macules, often symmetrical over the face, hands and body folds, with Wood lamp accentuation. Associated with other autoimmune disease, particularly autoimmune thyroid disease, type 1 diabetes, pernicious anaemia and Addison disease — so screening for these is part of the assessment.
• Albinism — melanocytes are present but cannot make pigment, most often from tyrosinase deficiency. Generalised hypopigmentation with ocular involvement: nystagmus, reduced acuity, photophobia, and a markedly raised lifetime risk of skin cancer.
• Melasma — acquired, symmetrical hyperpigmented patches on the face, driven by oestrogen and ultraviolet exposure; associated with pregnancy ("mask of pregnancy") and combined oral contraceptives. Sun protection is the foundation of treatment.
• Post-inflammatory hyperpigmentation follows acne, eczema or injury, is commoner in darker skin, and fades slowly.
• Tinea versicolor — Malassezia produces azelaic acid that inhibits tyrosinase, causing hypopigmented (or hyperpigmented) scaly macules that fail to tan; spaghetti-and-meatballs hyphae and spores on potassium hydroxide.
• Distinguish hypopigmentation (reduced pigment, as in pityriasis alba and tinea versicolor) from depigmentation (complete loss, as in vitiligo).

Autoimmune melanocyte destruction

• Vitiligo: CD8+ T-cell–mediated killing of melanocytes in genetically susceptible hosts (HLA and *NLRP1*/*PTPN22* associations). Non-modifiable risks: family history, personal or family autoimmunity (Hashimoto/Graves disease, type 1 diabetes, pernicious anaemia, Addison disease, alopecia areata). Modifiable triggers: skin trauma, friction, sunburn (Koebner phenomenon).
• Chemical leukoderma: phenols/catechols — classically monobenzyl ether of hydroquinone in rubber, adhesives and bleaching creams — are melanocyte-toxic and mimic vitiligo. Entirely occupational and modifiable.

Genetic failure of pigment synthesis (melanocytes present)

• Oculocutaneous albinism: autosomal recessive; OCA1 = tyrosinase mutation, OCA2 = P-protein, the commonest form worldwide.
• Syndromic albinism: Hermansky–Pudlak (albinism + platelet storage-pool bleeding + pulmonary fibrosis; enriched in Puerto Rican ancestry) and Chédiak–Higashi (LYST, giant granules, pyogenic infections).
• Piebaldism (KIT, congenital white forelock) and Waardenburg syndrome (PAX3; deafness, dystopia canthorum) — failure of melanoblast migration from the neural crest.

Increased melanogenesis

• Melasma: oestrogen/progesterone plus ultraviolet and visible light. Non-modifiable: female sex, Fitzpatrick skin types III–V, pregnancy predisposition. Modifiable: combined oral contraceptives, sun and heat exposure, photosensitising drugs, cosmetics.
• Post-inflammatory hyperpigmentation: any dermatitis, acne, lichen planus, burn or procedure; risk rises steeply with darker constitutive pigmentation.
• Drug- and endocrine-related: minocycline, amiodarone, hydroxychloroquine, chemotherapy (bleomycin flagellate pigmentation); ACTH excess in Addison disease and ectopic ACTH.

Infectious/inflammatory hypopigmentation

• Tinea versicolor: Malassezia furfur overgrowth favoured by heat, humidity, sweating, oily skin, adolescence, corticosteroids and immunosuppression — largely modifiable, and relapse is the rule in hot climates.
• Pityriasis alba (atopic children), leprosy (hypopigmented anaesthetic patch), and ash-leaf macules of tuberous sclerosis.

• Normal pigment unit: one melanocyte in the basal layer supplies ~30–40 keratinocytes. Tyrosinase converts tyrosine → DOPA → dopaquinone → melanin inside melanosomes, which are transferred to keratinocytes and capped over nuclei. Skin colour differences reflect melanosome size and dispersion, not melanocyte number — which is why disorders differ by which step fails.
• Vitiligo (melanocytes absent): oxidative stress in melanocytes releases heat-shock protein 70 and damage signals, driving an innate then IFN-γ/CXCL9–CXCL10–dependent CD8+ T-cell attack. Complete loss of the pigment unit gives depigmentation — chalk-white, not merely pale — with sharp borders, and Wood lamp accentuation because no epidermal melanin remains to absorb ultraviolet light. Melanocyte reservoirs in the hair follicle bulge explain perifollicular repigmentation with therapy and why glabrous skin (fingertips, lips) responds poorly. The same antigenic targets on epidermal, uveal and inner-ear melanocytes explain uveitis and hearing loss.
• Albinism (melanocytes present, pigment absent): tyrosinase or melanosomal transporter dysfunction halts melanin synthesis; melanocyte number is normal. Absent retinal pigment epithelium melanin misroutes optic fibres at the chiasm and prevents foveal development → nystagmus, reduced acuity, strabismus, photophobia — the ocular findings are developmental, not cosmetic. Loss of melanin's UV-absorbing and radical-scavenging function accelerates photocarcinogenesis.
• Melasma (melanocytes overactive): oestrogen, progesterone and UV/visible light upregulate tyrosinase and stem-cell factor/c-KIT signalling; there is also dermal solar elastosis, increased vascularity and mast cells, so pigment sits in the epidermis, dermis or both — the mixed dermal component is why melasma recurs and resists bleaching.
• Post-inflammatory hyperpigmentation: inflammatory prostaglandins and leukotrienes stimulate melanogenesis; basal-layer damage lets melanin drop into the dermis, where melanophages hold it for months (dermal pigmentary incontinence).
• Tinea versicolor: Malassezia dicarboxylic acids (azelaic acid) competitively inhibit tyrosinase, so affected skin cannot tan — lesions become most obvious after sun exposure.

Vitiligo

• Stem: a young adult, often with hypothyroidism or type 1 diabetes, notes spreading white patches. Sharply marginated, completely depigmented macules/patches, symmetrical over periorificial face, dorsal hands, elbows, knees, genitalia and axillae; leukotrichia (white hairs) predicts poor repigmentation. Segmental vitiligo is unilateral, dermatomal, early-onset and stable. New lesions along a scratch or surgical scar = Koebner phenomenon. Skin is otherwise normal — no scale, no atrophy, no anaesthesia.

Albinism

• Congenital diffuse white/cream skin, white-to-yellow hair, translucent or blue-grey irides with iris transillumination, foveal hypoplasia, horizontal nystagmus, photophobia and reduced visual acuity. Look for easy bruising/epistaxis (Hermansky–Pudlak) or recurrent pyogenic infections with giant cytoplasmic granules (Chédiak–Higashi).

Melasma

• Stem: a pregnant woman or a woman on combined oral contraceptives with Fitzpatrick type III–V skin. Symmetrical, irregularly bordered tan-to-brown patches on malar cheeks, forehead, upper lip (sparing the philtrum) and chin. Asymptomatic — no itch, no scale.

Post-inflammatory hyperpigmentation

• Brown-to-grey macules conforming exactly to the footprint of prior acne, eczema, lichen planus or a burn; darker and longer-lasting in richly pigmented skin. Grey-blue hue suggests dermal melanophages and a slow course.

Tinea versicolor

• Stem: an adolescent or young adult after summer, humidity or sweating. Numerous coalescing hypopigmented (or salmon/brown) macules on the upper trunk, shoulders and neck with fine furfuraceous scale elicited by stretching or scraping (evoked scale sign); mild or no itch; the patches "fail to tan."

Step 1 — clinical morphology plus Wood lamp (365 nm) at the bedside

• Vitiligo: bright blue-white accentuation with borders sharper under the lamp than in ambient light; confirms depigmentation and reveals subclinical lesions.
• Tinea versicolor: coppery-orange to yellow-green fluorescence in only a minority of cases — a negative lamp does not exclude it.
• Melasma: epidermal pigment is accentuated; dermal/mixed pigment is not — this predicts a poorer response to topical bleaching.
• Ash-leaf macules of tuberous sclerosis are also lamp-accentuated but are congenital and hypopigmented, not depigmented.

Step 2 — targeted confirmatory testing

• Potassium hydroxide preparation of scale is the test of choice for tinea versicolor: short hyphae with clustered yeast — spaghetti and meatballs. Culture is unhelpful (Malassezia is lipid-dependent).
• Skin biopsy is the gold standard when the diagnosis is unclear: vitiligo shows absent melanocytes (loss of Melan-A/MART-1 and S100 staining) with absent basal melanin on Fontana–Masson; albinism shows normal melanocyte numbers with absent pigment; post-inflammatory hyperpigmentation shows dermal melanophages.
• Sensory testing and nerve palpation on any hypopigmented patch when leprosy is plausible.

Vitiligo (AAD)

• First-line, limited disease: potent topical corticosteroids (e.g. betamethasone) for trunk/limbs, switching to a topical calcineurin inhibitor (tacrolimus ointment) on face, eyelids and intertriginous skin to avoid steroid atrophy.
• Topical JAK inhibitor: ruxolitinib cream is FDA-approved for non-segmental vitiligo in patients aged 12 and older — it blocks the IFN-γ/JAK–STAT axis driving melanocyte killing.
• Escalation: narrowband UVB phototherapy for widespread or rapidly progressive disease, often combined with topicals; short courses of oral corticosteroids (minipulse) are sometimes used to halt rapid progression.
• Surgical: melanocyte–keratinocyte suspension or punch/blister grafting for stable, segmental disease only.
• Depigmentation with monobenzyl ether of hydroquinone is a last resort for near-universal vitiligo — irreversible.
• Adjuncts: camouflage cosmetics, sunscreen, and screening/treatment of associated thyroid disease. Vitamin D and antioxidants are not substitutes for the above.

Disease-related

• Sunburn and photocarcinogenesis: depigmented vitiligo skin and albinotic skin lack melanin's UV shield. In albinism this produces early actinic keratoses and a markedly increased lifetime risk of squamous cell carcinoma, basal cell carcinoma and amelanotic melanoma — any new persistent ulcerated or crusted papule warrants biopsy.
• Permanent visual impairment in albinism from foveal hypoplasia and misrouted chiasmal fibres; nystagmus and low acuity do not improve with pigment.
• Extracutaneous melanocyte loss in vitiligo: uveitis (red painful eye with photophobia — urgent ophthalmology) and sensorineural hearing loss; consider Vogt–Koyanagi–Harada syndrome when vitiligo, poliosis, uveitis and meningismus coexist.
• Associated autoimmune endocrinopathy: undiagnosed Addison disease in a vitiligo patient can present as adrenal crisis — hypotension, hyponatraemia, hyperkalaemia — a true emergency; autoimmune thyroid disease and pernicious anaemia are commoner but non-urgent.
• Syndromic albinism emergencies: Hermansky–Pudlak platelet dense-body deficiency causes surgical and postpartum haemorrhage with a normal platelet count and prolonged bleeding time, plus progressive pulmonary fibrosis; Chédiak–Higashi accelerated phase is a haemophagocytic lymphohistiocytosis-like state — cytopenias, fever, hepatosplenomegaly — and is life-threatening.
• Psychosocial burden: depression, anxiety, social withdrawal and stigmatisation are the most frequent complications of vitiligo and melasma, and are disproportionate to body-surface area involved. Screen for mood disorder.
• Recurrence: tinea versicolor relapses frequently; melasma recurs with any sun or hormonal exposure.

Treatment-related

• Topical corticosteroids: atrophy, telangiectasia, striae, acneiform eruption; periocular use risks glaucoma and cataract.
• Calcineurin inhibitors: burning on application; boxed warning regarding theoretical malignancy risk.
• Phototherapy: burns, xerosis, photoaging; PUVA carries a cumulative cutaneous carcinoma risk.
• Hydroquinone: irritant dermatitis, confetti-like hypopigmentation, and exogenous ochronosis — paradoxical blue-black pigment with prolonged use.
• Monobenzone depigmentation: irreversible and generalised — never a reversible trial.
• Oral azoles: hepatotoxicity and CYP3A4 interactions; itraconazole has negative inotropic effects and is avoided in heart failure.

• ***Chalk-white with Wood lamp accentuation* = vitiligo (depigmentation); fails to tan with fine scale on the trunk = tinea versicolor (hypopigmentation).** Depigmented means melanocytes are gone; hypopigmented means they are still there but underperforming.
• The single best next step in new vitiligo is checking thyroid function with TSH and thyroid peroxidase antibodies. Autoimmune thyroid disease is the association examiners test most often; type 1 diabetes, pernicious anaemia and Addison disease are the runners-up.
• KOH prep is the next step for scaly hypopigmented trunk macules — spaghetti and meatballs short hyphae and spores. Fungal culture is the distractor; Malassezia is lipid-dependent and will not grow on routine media.
• Albinism has normal melanocyte numbers. The lesion is tyrosinase (OCA1) or melanosomal protein (OCA2) function. If the stem adds bleeding → Hermansky–Pudlak; giant granules in leukocytes with recurrent pyogenic infections → Chédiak–Higashi.
• Melasma = oestrogen + UV/visible light. Stop the combined oral contraceptive, mandate tinted broad-spectrum sunscreen, and treat with hydroquinone or the triple combination. Prolonged hydroquinone can cause exogenous ochronosis — blue-black pigment, a classic paradox.
• New white patches appearing in a scratch or scar = Koebner phenomenon; also seen in psoriasis and lichen planus.
• Ruxolitinib cream (topical JAK inhibitor) is FDA-approved for non-segmental vitiligo, reflecting the IFN-γ/CXCL10-driven CD8+ attack; narrowband UVB remains the escalation for widespread disease, and grafting is reserved for stable segmental vitiligo.
• **A hypopigmented patch that is anaesthetic is leprosy, not vitiligo** — test sensation and palpate peripheral nerves. Similarly, a congenital hypopigmented ash-leaf macule with seizures points to tuberous sclerosis.
• Tinea versicolor treatment failure is not the same as persistence of pale patches — repigmentation lags cure by months, so do not re-treat on colour alone.