Melasma & Acquired Hyperpigmentation

Acquired hyperpigmentation is excess melanin (or other pigment) deposited in skin that was previously normal. For NEET PG the workhorse topic is melasma — a chronic, relapsing, UV- and hormone-driven facial hypermelanosis — flanked by post-inflammatory hyperpigmentation, endocrine causes (Addison's), and drug-induced melanosis. The examiner loves Wood's lamp localisation, dermoscopy patterns, the triple-combination (Kligman) cream and the unglamorous truth that photoprotection is the real cornerstone.

Definitions & basic vocabulary

• Hyperpigmentation = increased skin colour due to excess pigment. The pigment is usually melanin but may be haemosiderin, drug metabolites or exogenous material.
• Hypermelanosis = specifically increased melanin. Two mechanistic flavours:
  • Melanotic (epidermal) — more melanin, normal melanocyte number (e.g. melasma epidermal type, freckle, café-au-lait macule).
  • Melanocytotic — increased melanocyte number (e.g. lentigo).
• Melasma (chloasma) = acquired, symmetrical, light-to-dark brown macular hypermelanosis of sun-exposed face, classically in women of reproductive age and in skin phototypes III–V (brown skin → very relevant to Indian patients).
• Post-inflammatory hyperpigmentation (PIH) = pigmentation following cutaneous inflammation/injury; commoner and more intense in darker skin.

High-yield: "Chloasma" / "mask of pregnancy" = melasma occurring in pregnancy. Same disease, eponymous trigger.

Classification of melasma

By distribution (clinical pattern)

Pattern	Area involved	Notes
Centrofacial	Forehead, cheeks, nose, upper lip, chin	Commonest pattern
Malar	Cheeks + nose	Second commonest
Mandibular	Ramus of mandible	Older patients; overlaps with poikiloderma of Civatte
Extrafacial	Forearms, neck, sternum	Post-menopausal, sun-exposed

By depth of pigment (the high-yield axis)

Type	Wood's lamp	Pigment location	Prognosis with treatment
Epidermal	Accentuated / enhanced contrast	Basal & suprabasal keratinocytes	Best response
Dermal	No accentuation (no enhancement)	Dermal melanophages	Poor response
Mixed	Some areas enhance, others do not	Both	Partial response
Indeterminate	Hard to see (very dark skin, type V–VI)	—	Variable

High-yield: Wood's lamp (UV-A ~365 nm) enhances epidermal pigment but does not enhance dermal pigment. Epidermal melasma therefore responds best to topical bleaching; dermal melasma is stubborn. Memorise: Epidermal Enhances.

Etiology & pathophysiology

Melasma is multifactorial — a genetically primed melanocyte over-reacting to hormonal and ultraviolet stimuli, now understood as a photoageing-linked disorder rather than simple pigmentation.

Trigger checklist (mnemonic "SHADE"):

• Sun / UV (most important; also visible light, esp. blue light → relevant for screens and why iron-oxide tinted sunscreens matter)
• Hormones — oestrogen & progesterone; pregnancy, oral contraceptive pills, hormone replacement therapy
• Autoimmune thyroid disease / thyroid dysfunction (association)
• Drugs & cosmetics — phototoxic drugs, photosensitising cosmetics
• Ethnic/genetic predisposition (Fitzpatrick III–V; positive family history in ~50%)

Pathophysiology highlights:

• Hyperfunctional melanocytes with increased melanin synthesis and transfer to keratinocytes; melanocyte number is not greatly increased.
• UV → increased α-MSH, stem cell factor (SCF), and upregulation of tyrosinase (rate-limiting enzyme of melanogenesis).
• Increased dermal vascularisation (VEGF) — melasma lesions are more vascular; this underlies the "vascular melasma" component and the recurrence after laser.
• Basement membrane damage allows melanin to "drop" into the dermis (dermal melanophages) → explains the chronic, treatment-resistant dermal component.
• Solar elastosis and senescent fibroblasts in lesional skin → melasma reframed as localised photoageing.

High-yield: Tyrosinase is the rate-limiting enzyme of melanogenesis and the molecular target of hydroquinone, arbutin, kojic acid and azelaic acid.

Clinical features

• Symmetrical, irregular, light-to-dark brown macules and patches with a serrated / geographic border.
• Sites: malar prominences, forehead, upper lip (spares the philtrum in a characteristic way), chin, nose.
• Asymptomatic (no itch, no scale) — purely cosmetic and psychologically distressing.
• Worsens with sun exposure and summer; may fade partially in winter.
• Onset often in 3rd–4th decade; strong female preponderance (M:F roughly 1:9), though men (~10%) do get it.

Quick clinical distinction from look-alikes: melasma is symmetrical, macular, non-scaly. Compare with the differentials below.

Diagnosis & investigation of choice

Melasma is a clinical diagnosis. Investigations help with depth and grading rather than confirmation.

Stepwise approach:

1. History → onset, OCP/pregnancy, sun habit, cosmetics, drugs, family history.
2. Clinical examination in good daylight → distribution pattern.
3. Wood's lamp → epidermal vs dermal vs mixed (drives prognosis & therapy). Investigation of choice for depth localisation.
4. Dermoscopy → pattern recognition + vascular component (see below).
5. MASI / mMASI score (Melasma Area and Severity Index) → objective severity & response monitoring.
6. Skin biopsy → rarely needed; reserved for atypical/diagnostic-doubt cases (shows increased epidermal melanin ± dermal melanophages, solar elastosis).

High-yield: Investigation of choice to differentiate epidermal from dermal melasma at the bedside = Wood's lamp. For research-grade depth, reflectance confocal microscopy is more accurate but not routine.

Dermoscopy of melasma (very testable)

• Pseudoreticular pigment network sparing follicular and sweat-duct openings (face has thin reticular network because of adnexal openings).
• Brown granules/globules = epidermal pigment.
• Bluish-grey colour / grey dots = dermal pigment (worse prognosis).
• Telangiectasias / increased vascularity = vascular component → caution with laser/aggressive Rx.
• Dermoscopy also screens for exogenous ochronosis (see complications): "blue-grey amorphous structures obliterating follicular openings."

Management & drug of choice

Treatment is a long game: photoprotection + topical depigmenting agent ± procedures, with realistic counselling about recurrence.

Tier 1 — Foundation (everyone)

• Broad-spectrum sunscreen is the mainstay and most important single intervention. Use SPF ≥ 30 (ideally 50+), PA+++, broad-spectrum covering UVA + UVB, reapplied 2–3 hourly.
• Tinted (iron-oxide) sunscreens block visible/blue light — superior in melasma, especially darker skin.
• Stop offending OCP/HRT where feasible; avoid photosensitising cosmetics; physical avoidance (hat, shade).

Tier 2 — Topical depigmenting (drug of choice)

• Triple-combination cream (Kligman's formula / modified Kligman) is the gold-standard first-line topical and the single most-tested "drug of choice".
  • Hydroquinone 2–4% (tyrosinase inhibitor) +
  • Tretinoin 0.05% (enhances penetration, increases epidermal turnover, reduces HQ oxidation) +
  • Topical corticosteroid (fluocinolone acetonide 0.01% — reduces irritation and melanocyte activity).
• Hydroquinone alone 2–4% is the prototype single agent (limit continuous use, watch for ochronosis).
• Non-hydroquinone alternatives (for maintenance, HQ-intolerant, pregnancy-safe options): azelaic acid 20% (pregnancy-safe), kojic acid, arbutin, niacinamide, vitamin C (ascorbic acid), cysteamine, tranexamic acid (topical).

High-yield: Triple combination = Hydroquinone + Tretinoin + (mild) Corticosteroid. Mnemonic "HTS" / "the Kligman trio." It is first-line; sunscreen is the cornerstone you must combine it with.

Tier 3 — Systemic & procedural (refractory / maintenance)

• Oral tranexamic acid 250 mg BD (≈ 500 mg/day) — increasingly favoured; works via plasmin inhibition → less arachidonic acid/α-MSH and reduced VEGF/angiogenesis. Screen for thromboembolic risk before prescribing.
• Chemical peels — glycolic acid, salicylic acid, lactic acid, Jessner's, TCA (low %). Adjunct to topicals; risk of PIH in dark skin if aggressive.
• Lasers / light — low-fluence Q-switched Nd:YAG ("laser toning"), picosecond lasers; use cautiously — high recurrence and risk of rebound/paradoxical hyperpigmentation. Lasers are NOT first-line.
• Microneedling as a drug-delivery adjunct (e.g. with tranexamic acid).

Treatment flow: Photoprotection (always) → Triple combination cream → add chemical peel / oral tranexamic acid if inadequate → laser only in refractory, vascular-quiet cases → indefinite maintenance with non-HQ agents + sunscreen.

High-yield: Hydroquinone should be used in pulses (e.g. 8–12 weeks on, then break), not continuously, to avoid exogenous ochronosis. Azelaic acid is the go-to in pregnancy (HQ and tretinoin are best avoided).

Other important acquired hyperpigmentations

Post-inflammatory hyperpigmentation (PIH)

• Follows acne, eczema, lichen planus, drug reactions, burns, procedures.
• Two patterns: epidermal PIH (tan-brown, fades over months) and dermal PIH (grey-blue, melanin in dermal macrophages, can be near-permanent).
• Management: treat the underlying inflammation first, photoprotection, then topical lightening (HQ, azelaic acid, retinoid, chemical peels). Lichen planus pigmentosus is a recognised dermal variant.

Addison's disease (and other endocrine pigmentation)

• Generalised hyperpigmentation that is accentuated at: palmar creases, knuckles, oral/buccal mucosa, scars (new scars pigment), pressure points, areolae, and sun-exposed sites.
• Mechanism: low cortisol → loss of negative feedback → high ACTH; POMC-derived ACTH and α-MSH stimulate melanocytes (ACTH shares the melanocortin pathway).
• Associated: hypotension, hyponatraemia, hyperkalaemia, weight loss, salt craving.
• Investigation of choice: short Synacthen (ACTH stimulation) test; 0800h cortisol + ACTH screening.

High-yield: Buccal mucosa and palmar crease pigmentation + hypotension + hyponatraemia/hyperkalaemia = Addison's. Pigmentation is driven by ACTH/α-MSH, not cortisol itself.

Drug-induced melanosis / pigmentation

Drug	Colour / site	Mechanism clue
Amiodarone	Slate-grey, photodistributed (face)	Lipofuscin-drug complex; photosensitivity
Minocycline	Blue-grey (shins, scars, sclera, teeth, bone)	Drug-pigment/iron complexes
Chloroquine / hydroxychloroquine, antimalarials	Blue-grey (shins, face, palate)	Melanin + drug
Chlorpromazine / phenothiazines	Slate-grey, sun-exposed	Photosensitised melanin
Heavy metals — silver (argyria)	Diffuse slate-blue/grey	Silver deposition
Bleomycin	Flagellate (whip-like linear) pigmentation on trunk	Classic eponymous pattern
Busulfan, cyclophosphamide, 5-FU	Diffuse / serpentine	Chemotherapy melanosis
Zidovudine (AZT)	Nail and mucosal pigmentation	—

High-yield: Flagellate (whiplash) hyperpigmentation → bleomycin. Slate-grey photodistributed face → amiodarone. Blue-grey shins/scars/teeth → minocycline.

Exogenous ochronosis

• Paradoxical blue-black hyperpigmentation from prolonged topical hydroquinone (the very drug used to treat melasma).
• Histology/dermoscopy: ochre-coloured banana-shaped fibres in dermis; dermoscopy shows blue-grey amorphous areas obliterating follicular openings.
• Management: stop hydroquinone; difficult to treat. Differentiate from endogenous ochronosis (alkaptonuria — homogentisic acid).

Complications

• Psychological/cosmetic distress and impaired quality of life (the main "complication" of melasma).
• Recurrence/relapse — the rule, not the exception; lifelong photoprotection needed.
• Exogenous ochronosis and HQ-related leukoderma/irritant dermatitis from over-use.
• Topical steroid side-effects from triple cream misuse: atrophy, telangiectasia, perioral dermatitis, steroid rosacea (huge problem in India with OTC steroid-containing fairness creams).
• Post-laser rebound hyperpigmentation / mottled hypopigmentation.
• For PIH: cosmetic disfigurement, sometimes permanent (dermal).

Key differentials

Condition	Distinguishing clue
Melasma	Symmetrical, brown, macular, non-scaly, sun-exposed face, female
Post-inflammatory hyperpigmentation	History of preceding dermatosis/injury; follows lesion outline
Riehl's melanosis (pigmented contact dermatitis)	Reticulate grey-brown, cosmetic allergen, often forehead/temples
Erythema dyschromicum perstans (ashy dermatosis)	Ashy-grey macules with (early) erythematous active border, trunk
Lichen planus pigmentosus	Dark-brown/violaceous, flexures & face, dermal melanin
Naevus of Ota	Unilateral, blue-grey, V1/V2 trigeminal + scleral pigmentation; congenital/dermal
Hori's naevus (ABNOM)	Bilateral acquired naevus-of-Ota-like macules, dermal, no mucosal involvement
Freckles / lentigines / café-au-lait	Smaller, well-defined; lentigo = increased melanocytes
Drug-induced melanosis	Drug history; often grey-blue, photodistributed
Poikiloderma of Civatte	Reticulate erythema + pigment + atrophy on sides of neck, sparing submental shadow

High-yield: Naevus of Ota = unilateral + scleral/ocular pigment (blue-grey). Hori's naevus = bilateral, no mucosal/scleral involvement, acquired in adulthood. Both are dermal → poor topical response, laser-responsive (unlike melasma).

Recently asked / exam angle

• Wood's lamp interpretation: "Pigment is accentuated under Wood's lamp" → epidermal melasma → best topical response. (Repeated favourite.)
• Drug of choice / triple combination: identify the three components (HQ + tretinoin + steroid) and the role of each.
• Cornerstone of management: sunscreen / photoprotection (not laser, not HQ alone).
• Exogenous ochronosis linked to prolonged hydroquinone — image/clinical vignette.
• Flagellate pigmentation → bleomycin; slate-grey photodistributed → amiodarone; blue-grey shins/teeth → minocycline — single-best-answer drug matching.
• Addison's pigmentation mechanism = ACTH/α-MSH, with buccal mucosa + palmar crease involvement; short Synacthen test.
• Oral tranexamic acid mechanism (plasmin/VEGF) and the need to screen for thromboembolism.
• Dermoscopy: pseudoreticular network sparing follicular openings; grey dots = dermal/worse prognosis.
• Pregnancy-safe lightening agent = azelaic acid (avoid HQ + retinoids).
• MASI/mMASI as the severity-scoring tool.

Rapid revision

1. Melasma = symmetrical, brown, macular facial hypermelanosis; triggers = sun, hormones (pregnancy/OCP), genetics; phototypes III–V.
2. Wood's lamp enhances epidermal pigment, not dermal — epidermal type responds best.
3. Sunscreen (broad-spectrum, tinted/iron-oxide for visible light) is the cornerstone.
4. First-line topical = triple combination: hydroquinone + tretinoin + corticosteroid (Kligman/modified Kligman).
5. Tyrosinase is the rate-limiting enzyme and main drug target.
6. Oral tranexamic acid 250 mg BD for refractory melasma — works via plasmin/VEGF; screen for thrombosis.
7. Azelaic acid 20% = pregnancy-safe depigmenting agent.
8. Prolonged hydroquinone → exogenous ochronosis (blue-black; banana-shaped dermal fibres) — use HQ in pulses.
9. Lasers are not first-line; high recurrence and risk of rebound pigmentation in melasma.
10. Addison's: generalised pigmentation + buccal mucosa + palmar creases; driven by ACTH/α-MSH; diagnose with short Synacthen test.
11. Bleomycin → flagellate pigmentation; amiodarone → slate-grey photodistributed face; minocycline → blue-grey shins/teeth/sclera.
12. Naevus of Ota = unilateral + ocular pigment; Hori's naevus = bilateral, no eye/mucosa, acquired — both dermal, laser-responsive.