Melasma

• Melasma is a photoageing disorder in genetically predisposed individuals that presents as a
  • bilateral, blotchy, brownish facial pigmentation

Differential diagnosis of melasma
Condition	Age of onset	Location	Clinical presentation
Acanthosis nigricans	Any age	Malar region; tends to spare the zygoma	Symmetric hyperpigmented plaques; past/family history of diabetes and/or obesity
Acquired dermal macular hyperpigmentation	Any age, but more common at 30–40 years	Face, neck and proximal extremities	Raised erythematous margins, occasional moderate pruritus with some hypopigmentation on a greyish background
Actinic lichen planus	Any age	Sun-exposed sites: face, neck and backs of the hands	Erythematous to violaceous flat-topped papules that are pruritic and polygonal; more common in darker skin
Discoid lupus erythematosus	Any age	Malar and periorbital regions	Patches of facial skin atrophy with annular, mildly elevated erythema
Medication-induced pigmentation*	Any age	Usually face and arms	Slate-grey colour ± involvement of other regions (eg shins, scar sites, mucosal membranes)
Ephelides (freckles)	Any age	Sites of sun exposure	1–10 mm well-demarcated hyperpigmented round/oval macules
Frictional melanosis	Any age	Any site	Due to excessive, repeated mechanical stimulation (ie habit of rubbing)
Hori’s macules	20–70 years	Forehead, temples, upper eyelids and alar of nose	Bilateral and symmetrical small, greyish brown to blue-grey spots on the prominence of the cheeks and less often the temples, nose, eyelids, and forehead; mainly affects Asian women
Naevus of Ota	Infancy to adolescence	First two branches of the trigeminal nerve	Blue-to-grey speckled or mottled coalescing macules or patches affecting the forehead, temple, malar area or periorbital skin; usually unilateral
Ochronosis (exogenous) from hydroquinone use	Any age	Sites of prior hydroquinone use	Blue-black hyperpigmentation
Poikiloderma of Civatte	30 years and older	Sides of neck, lateral cheeks and upper chest	Linear telangiectasia, erythema, mottled hyperpigmentation, and superficial atrophy in a reticular pattern, symmetrically affecting sun-exposed areas; more common in women than men
Post-inflammatory hyperpigmentation	Any age	Any site	Prior history of erythema or rash in area
Solar lentigines	Any age	Sites of sun exposure	1–20 mm well-demarcated hyperpigmented round/oval macules
*Includes medications such as minocycline, amiodarone, antimalarials, heavy metals, antiretrovirals, antipsychotics, clofazimine and imatinib

Overview

Melasma is a common skin condition characterized by overproduction of melanin by melanocytes (pigment cells), leading to brown or gray-brown patches on the skin. It is:

• More common in women than in men.
• Typically occurs between the ages of 20 and 40 years.
• Most prevalent in individuals who tan easily or have naturally brown skin (Fitzpatrick skin phototypes III, IV).
• Less common in people with fair skin (Fitzpatrick types I, II) or black skin (Fitzpatrick types V, VI).

Factors Implicated

1. Family History:
   • Approximately 60% of individuals with melasma report having affected family members.
2. Sun Exposure:
   • Ultraviolet (UV) and visible light exposure promote melanin production.
3. Hormones:
   • Pregnancy.
   • Estrogen/progesterone-containing oral contraceptives.
   • Intrauterine devices (IUDs).
   • Hormonal implants.
   • Hormone replacement therapy.
   • Thyroid disorders.
4. Medications and Scented Products:
   • Certain medications and products with fragrance can trigger melasma.

Treatment

General Measures

1. Identify and Avoid Triggers:
   • Identify factors that exacerbate symptoms and avoid them when possible.
2. Sun Protection:
   • Prioritize lifelong light protection, including against visible light.
   • Wear a broad-brimmed hat outdoors on sunny days.
   • Use broad-spectrum sunscreen with SPF 50+ that protects against UVA, UVB, and visible light, applied daily to the whole face year-round. Sunscreens containing iron oxides are preferred as they screen out visible light.
3. Skincare:
   • Use a mild cleanser.
   • If the skin is dry, use a non-perfumed moisturizer.
   • Cosmetic camouflage (makeup) can be used to disguise pigmentation. Concealers and color correctors can be helpful.
4. Hormonal Contraception:
   • Consider discontinuing hormonal contraception if permissible and after consultation with a healthcare provider.

Therapeutic Agents

• The most common therapeutic agents used in treating melasma are those that inhibit melanin production by decreasing melanogenesis and melanocyte proliferation.

Topical and systemic agents available for the treatment of melasma
Agent	Mechanism of action	Dosing	Side effects	Comments
Topical agents
Kligman’s formula (hydroquinone/ tretinoin/ dexamethasone)	Inhibits tyrosinase; increases epidermal keratinocyte turnover; anti-inflammatory	5%/0.025–0.05%/0.1% twice daily for three weeks	Skin irritation, erythema, telangiectasia, hyperpigmentation following irritant dermatitis		The gold standard of treatment. Start infrequent application and titrate up as tolerated to minimise irritant dermatitis. Best to initiate treatment in the winter in Australia. Treatment duration is 3–4 weeks, followed by review for clinical efficacy. Maintenance therapy will be necessary with non-hydroquinone therapies or fixed triple combination intermittently, twice a week or less often.
Hydroquinone	Inhibits tyrosinase	2–5% daily	Erythema, burning, itching, irritation and onchronosis with high doses or extended use		Can be used in combination. Gold standard of treatment in combination therapy. Avoid in pregnancy.
Azelaic acid	Inhibits tyrosinase	5–20% twice daily	Stinging, burning, pruritus and dryness		Good response for treatment of epidermal melasma.
Kojic acid	Inhibits tyrosinase	1–2% daily	Skin irritation, contact dermatitis and increased skin sensitisation		Mixed results.
Ascorbic acid (vitamin C)	Inhibits reactive oxygen species	5–15% daily	No significant adverse effects		Well tolerated, but highly unstable; best in combination.
Cysteamine	Inhibits tyrosinase	5% daily	No significant adverse effects		Effective for treatment of epidermal melasma.
Metimazole (antithyroid medication)	Potent peroxidase inhibitor; blocks melanin synthesis	5% daily	No significant adverse effects		Avoid in pregnancy (especially first trimester). No adverse events in neonates during lactation.
Tranexamic acid	Blocks binding of plasminogen to keratinocytes	2–5% twice daily	Erythema, scaling, dryness and irritation		Improvement in melasma.
Glutathione	Decreases tyrosinase to skew conversion of eumelanin to pheomelanin	2% daily	No significant adverse effects		Inferior to hydroquinone and combination therapy.
Iron oxide sunscreens	Blocks visible light	SPF 50+	No significant adverse effects		Well tolerated, showing improvement in mild melasma.
Tretinoin	Increases epidermal keratinocyte turnover	0.025–0.05% daily	Irritant dermatitis with occasional contact dermatitis and photosensitisation		Often used in combination. Inferior to combination therapy if used alone. Start with lower strength.
Corticosteroid treatments (hydrocortisone)	Anti-inflammatory; nonselectively inhibits melanogenesis	1% (variable) daily	Telangiectasias, epidermal atrophy, steroid-induced acne, striae and hypopigmentation		Work well to fade colour quickly and treat contact dermatitis, but potent steroids should be avoided on the face.
Systemic agents
Tranexamic acid	Blocks binding of plasminogen to keratinocytes and decreases prostaglandin and vascular endothelial growth factors	500–750 mg daily	Headaches, hypomenorrhea, mild abdominal discomfort, and transient skin irritation		Approximately 10–40% reduction in melasma but high rate of relapse within two months of cessation. Tranexamic acid may increase thromboembolic risk, so it is important to assess patients.
Polypodium leucotomos extract	Increases matrix metalloproteinase expression and increases cell structural integrity during ultraviolet damage	240 mg three times daily	No significant adverse effects		Weak evidence for significant improvement in melasma.
Glutathione	Decreases tyrosinase to skew conversion of eumelanin to pheomelanin	500 mg daily	Potentially severe adverse effects include possible liver, renal and thyroid dysfunction		Variable results; only effective in some parts of the body and do not elicit long-lasting effects.
Carotenoids (lutein/zeaxanthin)	Antioxidants; may inhibit lipid peroxidation and quench singlet oxygen	10 mg/2 mg daily	Skin discolouration, but reversible with discontinuation		Significant improvement in melasma and reduces erythema.