A 40 years old female presents with melasma from past 4 years

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Melasma - Clinical Overview

Classic melasma showing symmetric hyperpigmented patches over the malar prominences (Andrews' Diseases of the Skin)

Definition

Melasma (syn. chloasma, "mask of pregnancy") is a common acquired disorder of symmetric, hyperpigmented patches with irregular outlines, occurring most commonly on the face. It represents dysregulated melanogenesis driven by UV exposure and sex hormones, with a chronic relapsing course.

Andrews' Diseases of the Skin, p. 993
Dermatology 2-Volume Set 5e, p. 1343

Epidemiology & Risk Factors

Factor	Detail
Sex	>90% female; F:M ~9:1
Age	Young to middle-aged adults (peak 30s-40s)
Skin type	Fitzpatrick IV-V most affected; Hispanics, East/Southeast/South Asians, Black, Middle Eastern
Triggers	Sun exposure (primary), pregnancy, oral contraceptives (OCP), HRT
Other	Phenytoin, finasteride therapy, endocrinologic disorders

In this 40-year-old female, key questions include OCP use, pregnancy history, sun exposure history, and Fitzpatrick skin type.

Pathogenesis

UV exposure is the primary trigger: melasma affects sun-exposed areas, worsens in summer, patients have lower MED (minimal erythema dose), and solar elastosis is more marked in melasma-affected skin
Wnt signaling: Melasma skin has reduced WIF-1 (Wnt antagonist) expression → increased Wnt → stimulates melanogenesis
Hormonal influence: OCP, HRT, and pregnancy exacerbate via estrogen/progesterone-driven melanocyte stimulation; OCP-induced melasma often persists even after discontinuation
Genetic predisposition: Correlation with number of melanocytic nevi

Andrews' Diseases of the Skin, p. 993

Classification

By Location (Clinical Patterns)

Centrofacial - forehead, nose, upper lip, chin (most common)
Malar - cheeks, nose
Mandibular - jaw line

By Histological Depth

Type	Melanin Location	Wood's Lamp	Treatment Response
Epidermal	Basal & suprabasal epidermis	Enhanced (accentuated)	Better
Dermal	Within melanophages	Not enhanced	Poor
Mixed	Both layers	Variable	Intermediate

Note: Most cases show both epidermal and dermal melanin on histology and confocal microscopy - pure classification is unreliable. Dermal deposits respond poorly to topical agents.

Investigations / Workup

Wood's lamp examination - helps broadly categorize (though unreliable for definitive typing)
Dermatoscopy - useful to assess depth and rule out other pigmented lesions
Dermoscopy findings: pseudonetwork of hyperpigmentation, telangiectasias in sun-damaged skin
History: OCP use, pregnancy, sun habits, topical agents used
Consider: ANA, thyroid antibodies (associated autoimmune conditions occasionally reported)
Biopsy: Rarely needed; if diagnosis uncertain or exogenous ochronosis suspected

Differential Diagnosis

Condition	Distinguishing Features
Drug-induced hyperpigmentation	Less patterned, less irregular outline; history of offending drug (doxycycline, amiodarone)
Post-inflammatory hyperpigmentation (PIH)	History of inflammation; may not follow facial distribution
Riehl melanosis (Pigmented contact dermatitis)	Sites of cosmetic contact; brown-grey, lichenoid on histology
Ota's nevus / Horii nevus	Asian women; grey-blue macules; dermal melanocytes on histology
Lichen planus pigmentosus	Temples/preauricular; coexistent LP lesions (~20%)
Erythema dyschromicum perstans	Slate-grey, involves sun-protected areas too
Exogenous ochronosis	Progressive darkening after HQ use; banana-shaped deposits on histology
Actinic lichen planus	Fine scale, violaceous, lichenoid infiltrate

Treatment

All Patients (Foundation)

Broad-spectrum sunscreen SPF ≥30 daily (with physical blockers: zinc oxide or titanium dioxide; iron oxide added to block visible light via makeup/sunscreen)
Avoidance of sun exposure and tanning beds
Sun-protective hats and clothing
Discontinue OCP if possible
Camouflage makeup with iron oxide

Dermatology 2-Volume Set 5e, p. 1343

First-Line Topical Therapy

Kligman's Formula (Triple Combination) - gold standard:

Hydroquinone 4% + Tretinoin 0.05-0.1% + Mild topical corticosteroid (class 5-7)
Applied at bedtime
Used daily for 2-4 months, then reduced to 1-2x/week for maintenance
Most effective topical regimen available

Alternatives/Adjuncts:

Hydroquinone 4% alone (bedtime)
Azelaic acid 15-20%

Cautions: Overuse of the triple combo → fixed erythema, telangiectasias, acneiform eruptions, hypertrichosis. Prolonged HQ use → exogenous ochronosis. Corticosteroid overuse → perioral dermatitis, atrophy.

Adjunctive Topical Therapies

Agent	Concentration	Mechanism
L-ascorbic acid (Vitamin C)	10-15%	Inhibits tyrosinase, antioxidant
Kojic acid	1-4%	Inhibits tyrosinase
Tranexamic acid	2-5%	Inhibits plasminogen activator in keratinocytes → reduces prostaglandin-driven melanogenesis
Niacinamide	4%	Inhibits melanosome transfer

Adjunctive Oral Therapy

Tranexamic acid 250 mg BID for 8-12 weeks

Screen patients for thromboembolism risk factors before prescribing
Mechanism: inhibits UV-induced plasminogen activator activity in melanocytes and keratinocytes, reducing melanin synthesis

Recent meta-analyses confirm efficacy: a 2024 systematic review and a 2025 meta-analysis of intradermal tranexamic acid both support tranexamic acid (oral and intradermal) as effective for melasma management with good safety profiles. A 2025 meta-analysis also supports microneedling combined with tranexamic acid.

Second-Line (Procedural)

Chemical Peels (every 4-6 weeks):

Glycolic acid (start 30%, increase as tolerated)
Salicylic acid 20-30%
Note: Peels alone have not reproducibly enhanced 4% HQ efficacy and risk PIH if irritation occurs

Third-Line (Light & Laser)

Modality	Notes
Intense Pulsed Light (IPL)	Can improve melasma but high relapse rate
Non-ablative fractional laser	Best laser option; 60% of skin types III-V achieve 75-100% improvement; improves HQ penetration
Pulsed dye laser	May enhance topical combination therapy
Picosecond lasers	Emerging evidence
Q-switched Nd:YAG (low fluence)	Risk of increased pigmentation/punctate leukoderma - use cautiously
Er:YAG	Temporary improvement followed by PIH - generally avoided

Light-based therapies carry risk of PIH, hypopigmentation, and scarring in darker skin types (Fitzpatrick IV-V). Always do a test site first.

Long-Term Maintenance

Daily broad-spectrum sunscreen (non-negotiable)
Topical retinoid (continues to suppress recurrence)
Topical alpha-hydroxy acid (e.g. glycolic acid cream)
L-ascorbic acid, azelaic acid, kojic acid, or topical tranexamic acid

Prognosis & Counselling Points

Melasma is a chronic, relapsing condition - treatment suppresses but does not cure
OCP-induced melasma often persists despite discontinuation (unlike melasma of pregnancy, which usually clears within months of delivery)
Dermal melasma responds much more poorly than epidermal type
Realistic expectations are essential - partial improvement is more common than complete clearance
Even a Wood's lamp "epidermal" pattern often has some dermal component on histology
Sun protection alone can modestly improve melasma and is indispensable for any treatment to work

Dermatology 2-Volume Set 5e, p. 2859 | Andrews' Diseases of the Skin, p. 993-994

Summary for this patient: A 40-year-old female with 4 years of melasma is a classic presentation. Assess Fitzpatrick type, OCP use, sun exposure, and prior treatments. Start with rigorous photoprotection, Kligman's formula (if tolerated), and consider adding oral tranexamic acid 250 mg BID for 8-12 weeks (screen for VTE risk). If inadequate response after 3-6 months, escalate to chemical peels or non-ablative fractional laser. Counsel on chronic relapsing nature and need for maintenance therapy.

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