More Clinical Updates

Gonorrhea and syphilis are common sexually transmitted diseases (STDs) that share many characteristics.

Read more

Oral lichen planus (OLP) is as common as psoriasis and affects approximately 1-2% of the population. The disease develops in women more than twice as often as in men and most commonly occurs in the fifth to sixth decade of life, although the disease can sometimes affect children.

Read more

Recalcitrant cutaneous lupus erythematosus (CLE) causes patients considerable discomfort and often leads to disfigurement. Although the majority of CLE responds to the combination of sun protection, local glucocorticoids, and antimalarials, some cases require more aggressive therapy.

Read more

Solar ultraviolet (UV) radiation is the most important environmental factor involved in the pathogenesis of skin cancers.

Read more

Clinical Updates

Melasma: An update on laser and tranexamic acid treatment

Michelle Rodrigues, Amit G. Pandya, MD

Tuesday, December 17, 2013


Melasma is a common, acquired disorder of hyperpigmentation that occurs commonly in women with skin of color. Clinical patterns of disease include centrofacial, malar, mandibular and forearm types.1 Although the exact pathogenesis remains unknown, exacerbating factors include hormonal contraceptives, pregnancy, and ultraviolet-light exposure (Figure 1).


melasma 1

melasma 2

melasma 3

Figure 1: Melasma (images via

It is imperative that clinicians appreciate the significant and sometimes devastating psychological impact of melasma on the patient and treat it accordingly. Avoidance of exacerbating factors, including photoprotection (clothing, sunscreen, seeking shade, window protectors) is vital. In addition, cosmetic camouflage may be helpful, especially for women.1 Hydroquinone has long been used with good effect in melasma2 and its efficacy is undoubted.3 A plethora of other topical agents, including retinoids, ascorbic acid, azelaic acid and other 'natural' compounds and peels, have been described in the treatment of melasma,1 although combination hydroquinone (4%), tretinoin (0.05%) and flucinolone acetonide (0.01%) at night has been labeled as being the gold standard.4


 Table 1: Some topical agents used for hyperpigmentation

Drug Strengths Weakness
Ascorbic acid Less cutaneous irritation compared with hydroquinone Rapidly oxidized and highly unstable; not good as monotherapy
Azelaic acic Reasonable response for epidermal melasma Erythema, burning, stinging
Arbutin Less irritation than hydroquinon; may have sustained lightening effects (seen in studies for lentigines May cause paradoxical hyperpigmentation in concentrations >3%; no studies in melasma
Glycolic acid Inexpensive, available as cream or peel Cutaneous irritation; best in combination with other agents
Hydroquinone Excellent, well-established efficacy Cutaneous erythema, burning, itching, irritation
Kojic acid Less cutaneous irritation compared with retinoids and triple therapy Mixed efficacy in split-face trials; may be best in combination with hydroquinone
Licorice extract Good response in epidermal melasma More robust studies needed
Nicotinamide Effective for skin lightening Cutaneous irritation; more studies needed
Retinoids Good effect in melasma; other benefits on fine lines, texture of skin Cutatneous irritation, slow (months) to show improvement as monotherapy
Rucinol serum Satisfactory effect in melasma in one study 'Tolerable' side effects; more studies needed
Soy12 Modest effect on lentigines No studies on efficacy in melasma


With interest surrounding the advent of low-fluence Q-Switched (QS) laser for treating melasma, it is necessary to evaluate this treatment modality. In early studies, high-fluence neodymium-doped yttrium aluminum garnet (Nd-YAG) caused an unacceptably high incidence of post-inflammatory hyperpigmentation in those with skin of color.5,6 Since then, Polnikorn described a new technique (also known as 'laser toning') of repetitive sub-threshold pulse 1,064-nm QS-Nd-YAG laser for the treatment of melasma.7 This technique is thought to result in less melanocyte and keratinocyte damage8 and is now widely used in East Asia.

Wattanakari9 evaluated weekly low-fluence QS Nd-YAG for five weeks plus 2% hydroquinone nightly versus 2% hydroquinone alone for dermal and mixed melasma. Although excellent improvements were cited, mottled hypopigmentation, rebound hyperpigmentation and confetti-like hypopigmented macules were reported. A total of eight out of 24 subjects were noted to develop the latter problem, with relapse in all patients at Week 12.

Another randomised study8 reviewed three groups of patients. The first was treated with low-fluence QS Nd-YAG, the second with glycolic acid peels fortnightly (35-70% with pre-treatment retinoid priming) for 12 weeks and the third with high-fluence Nd-YAG fornightly.8 Best results were seen with low-fluence Nd-YAG, with high-fluence Nd-YAG causing the most adverse effects. All groups' MASI scores were increased at Week 12, indicating worsening of pigmentation.

Park et al.10 reported that combination QS Nd-YAG plus 30% glycolic acid peels every two weeks were superior to QS Nd-YAG treatment alone, but some recurrence was noted five months post-treatment. Mild adverse events (erythema, transient burning) were noted but no pigmentary problems were cited.

These and other studies suggest that low-fluence QS Nd-YAG laser may be useful in severe, refractory melasma when patients are carefully selected, risk factors for complications are excluded, and a combination of laser treatment and peels is utilized.11,12 The cost of treatment, inevitable relapse and the increasing side-effect profile with subsequent treatments urges the clinician to use multi-modality treatments and emphasize the need for ongoing photoprotection.


 Table 2: Lasers use in melasma

Laser Strengths Weakness
High fluence Nd-YAG NIL Worsens melasma
Low fluence QS Nd-YAG Modest - good effect on severe, refractory melasma Mottling, hyperpigmentation, confetti hypopigmentation
Intense Pulsed Light Good effect in skin phototype I-III Unpredictable pigmentary side effects in skin phototype IV-VI
Fractional resurfacing and copper bromide lasers Some good effects seen with melasma Further studies required


Oral tranexamic acid (TNA) is a novel treatment in melasma and also deserves some attention. Although traditionally used for bleeding diatheses and menorrhagia, it has been successfully used for the treatment of melasma.13 Although its mechanism of action is not entirely known, decreased tyrosinase activity in melanocytes is one possibility.14 Possible side effects include nausea, vomiting and diarrhea. Thromboembolism, pulmonary embolism and myocardial infarction have rarely been reported.

Cho et al.13 showed that TNA at a dose of 500 mg/day plus intense pulsed light, and QS Nd-YAG (four treatments) was superior to laser therapy alone. Shin et al.14 performed a randomized prospective trial, revealing that eight weeks of TNA at a dose of 750 mg/day enhanced the efficacy of low-fluence QS Nd-YAG laser therapy. Further studies are required to more fully evaluate this therapeutic option for melasma.

With the advent of new treatments, including lasers, and more therapeutic options on the horizon, it is an exciting time to be managing pigment disorders. This heralds the inevitable need for ongoing evidence-based research and trials.



1. Sheth VM, Pandya AG. Melasma: a comprehensive update: part I. J Am Acad Dermatol 2011;65:689-697; quiz 698.

2. Jimbow K, Obata H, Pathak MA, Fitzpatrick TB. Mechanism of depigmentation by hydroquinone. J Invest Dermatol 1974;62:436-449.

3. Ennes SBP, Paschoalick RC, Mota de Avelar Alchorne M. A double-blind, comparative, placebo-controlled study of the efficacy and tolerability of 4% hydroquinone as a depigmenting agent in melasma. J Dermatol Treat 2000;11:173-179. 

4. Sheth VM, Pandya AG. Melasma: a comprehensive update: part II. J Am Acad Dermatol 2011;65:699-713.

5. Tse Y, Levine VJ, McClain SA, Ashinoff R. The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser. A comparative study. J Dermatol Surg Oncol 1994;20:795-800.

6. Taylor CR, Anderson RR. Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby lase. J Dermatol Surg Oncol 1994;20:592-597.

7. Polnikorn N. Treatment of refractory dermal melasma with the MedLite C6 Q-switched Nd:YAG laser: two case reports. J Cosmet Laser Ther 2008;10:167-173.

8. Kar HK, Gupta L, Chauhan A. A comparative study on efficacy of high and low fluence Q-switched Nd:YAG laser and glycolic acid peel in melasma. Indian J Dermatol Venereol Leprol 2012;78:165-171.

9. Wattanakrai P, Mornchan R, Eimputh S. Low-fluence Q-switched neodymium-doped yttrium aluminum garnet (1,064 nm) laser for the treatment of facial melasma in Asians. Dermatol Surg 2012;36:76-87.

10. Park KY, Kim DH, Kim HK, et al. A randomized, observer-blinded, comparison of combined 1064-nm Q-switched neo-dymium-doped yttrium-aluminum-garnet laser plus 30% glycolic acid peel vs. laser monotherapy to treat melasma. Clin Exp Dermatol 2011;36:864-870.

11. Charu B, Hira N, Hemanta K, et al. A comparison of low-fluence 1064-nm Q-switched ND: YAG laser with topical 20% azelaic acid cream and their combination in melasma in Indian patients. J Cutan Aesthet Surg 2012;5:266-272.

12. Kim JE, Chang SE, Yeo UC, et al. Histopathological study of the treatment of melasma lesions using a low-fluence Q-switched 1064-nm neodymium:yttrium-aluminium-garnet laser. Clin Exp Dermatol 2013;38:167-171.

13. Cho HH, Choi M, Cho S, et al. Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS Nd:YAG laser. J Dermatolog Treat 2011;24:292-296.

14. Shin JU, Park J, Oh S, et al. Oral tranexamic acid enhances the efficacy of low-fluence 1064-nm quality-switched neodymium-doped yttrium aluminum garnet laser treatment for melasma in Koreans: a randomized, prospective trial. Dermatol Surg 2013;39(3 pt 1):435-442.