Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

pregnant

1st line – azelaic acid

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ACUTE
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pregnant
1st line – 

azelaic acid

Azelaic acid can be used during pregnancy.[40] However, it is usually recommended that treatment be deferred until the pregnancy is complete, because the hormonal influence will then be reduced.[41] 

Primary options

azelaic acid topical: (15-20%) apply to the affected area(s) twice daily

Plus – sun protection

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ACUTE
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pregnant
Plus – 

sun protection

Treatment recommended for ALL patients in selected patient group

To achieve maximum protection against ultraviolet (UV)A and UVB, a sun protection product containing a combination of agents is ideal.

Agents that protect against UVA include oxybenzone, avobenzone, and terephthalylidene dicamphor sulfonic acid.

Agents that protect against UVB include octocrylene, padimate O, octinoxate, and ensulizole.

The physical blockers (or inorganic sunscreens) titanium dioxide and zinc oxide offer protection against both UVA and UVB.

Recommended to be applied to the face every morning, with reapplication every 2 hours during intense sun exposure.

nonpregnant

1st line – topical therapy

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ACUTE
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nonpregnant
1st line – 

topical therapy

Lightening agents, such as hydroquinone and tretinoin, may be used as first-line therapy alone or as part of the Kligman formulation, which also contains a topical corticosteroid. Combination therapy may be better than any of the individual components used alone.[25] For example, the combination of fluocinolone 0.01%, hydroquinone 4%, and tretinoin 0.05% (modified Kligman formula) has shown significantly greater efficacy compared with hydroquinone 4% alone.[1][26][27] Maintenance therapy with triple combination for 6 months after initial management has been suggested to prevent relapses.[28][29]

Topical corticosteroids can be used in combination topical therapy (i.e., Kligman formulas), primarily to reduce irritation, although they do cause some skin lightening as well.

Long-term use of corticosteroids on the face (generally >12 weeks) can cause skin atrophy, telangiectasias, and/or an acneiform eruption.[1][39]

Azelaic acid is also used as a lightening agent in concentrations of 15% to 20%.[30][31][32]

Azelaic acid in combination with hydroquinone 5% has shown significant improvement in the Melasma Area and Severity Index (MASI) score; however, it was shown to have more irritative adverse effects.[53]

An alternative topical treatment is arbutin, a glycosylated hydroquinone available in many skin-lightening formulations.[38]

Hydroquinone-containing formulations should only be used for up to 8 weeks.

Consult pharmacist: some products may need to be specially compounded, as they are not available as a proprietary product.

Primary options

Kligman formula

dexamethasone/hydroquinone/tretinoin topical: (0.1%/5%/0.1%) apply to the affected area(s) once daily at night

More

OR

Modified Kligman formula

fluocinolone/hydroquinone/tretinoin topical: (0.01%/4%/0.05%) apply to the affected area(s) once daily at night

More

Secondary options

hydroquinone topical: (2-4%) apply to the affected area(s) twice daily

OR

tretinoin topical: (0.05 to 0.1%) apply to the affected area(s) once daily at night

OR

azelaic acid topical: (15-20%) apply to the affected area(s) twice daily

OR

arbutin topical: consult product literature for guidance on dose

Plus – sun protection

Back
ACUTE
|
nonpregnant
Plus – 

sun protection

Treatment recommended for ALL patients in selected patient group

To achieve maximum protection against UVA and UVB, a sun protection product containing a combination of agents is ideal.

Agents that protect against UVA include oxybenzone, avobenzone, and terephthalylidene dicamphor sulfonic acid.

Agents that protect against UVB include octocrylene, padimate O, octinoxate, and ensulizole.

The physical blockers (or inorganic sunscreens) titanium dioxide and zinc oxide offer protection against both UVA and UVB.

Recommended to be applied to the face every morning, with reapplication every 2 hours during intense sun exposure.

2nd line – chemical peels

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ACUTE
|
nonpregnant
2nd line – 

chemical peels

Chemical peels may be used alone or in combination with topical therapy, if tolerated, as a second-line therapy in nonpregnant people with melasma for whom topical therapies are ineffective.

Glycolic acid (50% to 80%), salicylic acid (20% to 35%), and trichloroacetic acid (20% to 50%) are the usual formulations used.

With higher concentrations of trichloroacetic acid, there is a risk of hyperpigmentation; preconditioning of the skin with hydroquinone and/or tretinoin may reduce this risk.

Salicylic acid peels are not effective when added to twice-daily hydroquinone 4%.[54]

Peels must be performed by trained practitioners only. Refer to dermatologist.

Consider – topical therapy

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ACUTE
|
nonpregnant
Consider – 

topical therapy

Treatment recommended for SOME patients in selected patient group

Lightening agents, such as hydroquinone and tretinoin, may be used alone or as part of the Kligman formulation, which also contains a topical corticosteroid. Combination therapy may be better than any of the individual components used alone.[25] For example, the combination of fluocinolone 0.01%, hydroquinone 4%, and tretinoin 0.05% (modified Kligman formula) has shown significantly greater efficacy compared with hydroquinone 4% alone.[1][26][27] Maintenance therapy with triple combination for 6 months after initial management has been suggested to prevent relapses.[28][29]

Topical corticosteroids can be used in combination topical therapy (i.e., Kligman formulas), primarily to reduce irritation, although they do cause some skin lightening as well.

Long-term use of corticosteroids on the face (generally >12 weeks) can cause skin atrophy, telangiectasias, and/or an acneiform eruption.[1][39]

Azelaic acid is also used as a lightening agent in concentrations of 15% to 20%.[30][31][32]

Azelaic acid in combination with hydroquinone 5% has shown significant improvement in the MASI score; however, it was shown to have more irritative adverse effects.[53]

Kojic acid, which is produced by Penicillium and Aspergillus species of molds, chelates copper and causes inactivation of tyrosinase. It can be used alone or in combination with other compounds; when used in combination with hydroquinone 5%, there is a synergistic effect and subsequent improvement in the MASI score.[33] However, long-term studies show kojic acid has high irritant potential, and it is mutagenic in the Ames test.[34][35]

Topical vitamin C (ascorbic acid) serums are often used in the treatment of melasma. Ascorbic acid decreases melanogenesis, prevents the production of free radicals, and offers some photoprotection. One trial showed 5% ascorbic acid to be equivalent to 4% hydroquinone in treating melasma; ascorbic acid was also associated with fewer adverse effects than hydroquinone.[36] When compared with glycolic acid 70% peel, nanosome vitamin C demonstrated improved efficacy with fewer side effects.[37]

An alternative topical treatment is arbutin, a glycosylated hydroquinone available in many skin-lightening formulations.[38]

Hydroquinone-containing formulations should only be used for up to 8 weeks.

Consult pharmacist: some products may need to be specially compounded, as they are not available as a proprietary product.

Primary options

Kligman formula

dexamethasone/hydroquinone/tretinoin topical: (0.1%/5%/0.1%) apply to the affected area(s) once daily at night

More

OR

Modified Kligman formula

fluocinolone/hydroquinone/tretinoin topical: (0.01%/4%/0.05%) apply to the affected area(s) once daily at night

More

Secondary options

hydroquinone topical: (2-4%) apply to the affected area(s) twice daily

OR

tretinoin topical: (0.05 to 0.1%) apply to the affected area(s) once daily at night

OR

azelaic acid topical: (15-20%) apply to the affected area(s) twice daily

OR

kojic acid topical: apply to the affected area(s) once daily at night

OR

vitamin C topical: consult product literature for guidance on dose

OR

arbutin topical: consult product literature for guidance on dose

Plus – sun protection

Back
ACUTE
|
nonpregnant
Plus – 

sun protection

Treatment recommended for ALL patients in selected patient group

To achieve maximum protection against UVA and UVB, a sun protection product containing a combination of agents is ideal.

Agents that protect against UVA include oxybenzone, avobenzone, and terephthalylidene dicamphor sulfonic acid.

Agents that protect against UVB include octocrylene, padimate O, octinoxate, and ensulizole.

The physical blockers (or inorganic sunscreens) titanium dioxide and zinc oxide offer protection against both UVA and UVB.

Recommended to be applied to the face every morning, with reapplication every 2 hours during intense sun exposure.

3rd line – cryotherapy, dermabrasion, laser therapy, or light therapy

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ACUTE
|
nonpregnant
3rd line – 

cryotherapy, dermabrasion, laser therapy, or light therapy

Cryotherapy using liquid nitrogen is effective because melanocytes are more susceptible to freezing than are other cells in the skin. This modality is best used in skin types I and II, as there is less risk of hyperpigmentation of normal skin.

The Q-switched alexandrite laser and the CO2 laser as combined therapy may be better than the Q-switched alexandrite laser alone.[46][47]

Dermabrasion is usually reserved for treatment of dermal melasma.

Intense pulsed light (IPL) works better for epidermal than for dermal melasma. Two to four pulses are used. In people for whom other treatments are ineffective, a single session of IPL and topical treatment with triple combination therapy has shown better response rates when compared with triple combination therapy.[55]

Fractional photothermolysis has demonstrated improvement in melasma following treatment.[48] It lowers the concentration of melanin granules and number of melanocytes.[50]

The variable square pulse (VSP) Er:YAG laser has been used as a treatment option in affected patients, resulting in significant improvement in the MASI score with less downtime, no crust formation, and less chance of adverse effects.[51]

Postinflammatory hyperpigmentation is common following laser therapy, but it is usually transient and can be managed with pre- and post-treatment hydroquinone therapy.[52]

Plus – sun protection

Back
ACUTE
|
nonpregnant
Plus – 

sun protection

Treatment recommended for ALL patients in selected patient group

To achieve maximum protection against UVA and UVB, a sun protection product containing a combination of agents is ideal.

Agents that protect against UVA include oxybenzone, avobenzone, and terephthalylidene dicamphor sulfonic acid.

Agents that protect against UVB include octocrylene, padimate O, octinoxate, and ensulizole.

The physical blockers (or inorganic sunscreens) titanium dioxide and zinc oxide offer protection against both UVA and UVB.

Recommended to be applied to the face every morning, with reapplication every 2 hours during intense sun exposure.

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer