CUSTOM DERMATOLOGY SEARCH:
Melasma and Post Inflammatory Hyperpigmentation: Management Update and Expert Opinion
Bryan Sofen, MD1; Giselle Prado, BS2; Jason Emer, MD3
Dyschromia is a frequent complaint in the cosmetic consultation as it is psychologically distressing and may be a signal of systemic changes (e.g., hormones, sun sensitivity/autoimmune, medications).1 Although dyschromia is more commonly reported in those with darker or diverse skin types, there is an increasing number of patients of all skin types seen in practice presenting with irregular macules and patches of hyper and hypopigmentation from improperly performed cosmetic procedures by non-core or untrained physicians inducing color changes (Figures 1a and 1b). Given the degree of importance patients place on a clear complexion with regards to color and tone, we set forth to describe updated treatment options for melasma and post-inflammatory hyperpigmentation (PIH) to guide proper management.
The treatment of melasma is frustrating due to its relapsing nature, few therapies offering a cure, and a struggle for successful preventative options. Alternatively, PIH can be prevented and often clears spontaneously on its own despite therapies that are available. Photoprotection and topical medical treatments are critical to the management of both entities in order to suppress melanogenesis (Table 1). In addition, medical treatments (both topical and procedural) work to aid in the removal of excess melanin that is already deposited.
Photoprotection underscores all treatment modalities for disorders of pigmentation, particularly melasma. Without photoprotection, minimal benefit will be seen with any other therapeutic option. UVB (290-315 nm), UVA (315-400 nm), and even visible light (400-700 nm) all stimulate melanocytes to produce melanin and in some instances can overproduce observable pigmentation.6 While the lower wavelength UVB has the highest energy of this group and is the most erythemogenic, both UVA and visible light have a greater impact on stimulating melanogenesis and creating more chronic pigmentation.7 Broadspectrum sun protection against both UVA and UVB is critical, with physical blockers such as those with zinc or titanium dioxide the most recommended; however, sunscreens with the addition of chemical photosensitizers such as avobenzone (Parsol® 1789), octocrylene (Milestab™ 3039), oxybenzone (Helioplex®), and ecamsule (Mexoryl™) can increase the spectrum of protection by decreasing the production of free radicals while remaining photostable and absorbative. Many broad-spectrum sunscreens do not fully protect against the visible light spectrum that may contribute to pigmentary exacerbation; this is why compounds such as Tinosorb® M (not available in the United States) are added. Tinosorb® M increases the stability of other UV filters (like octinoxate, Eusolex®/Uvinul®) and has an inherent ability to reflect and scatter most wavelengths (with the majority being UVA and UVB). Additional benefit has been seen in sunscreens tinted with compounds such as iron oxide that also protect against visible light.8 Sun-protective clothing and broad rimmed hats are also key components to a comprehensive photoprotection strategy. Additionally, Polypodium leucotomos (fern extract, Heliocare®) is an oral antioxidant that has shown photoprotective effects and is recommended by the authors for all patients with pigmentary concerns or those undergoing any laser therapy.9-10
Hydroquinone and Combination Therapy
The best-studied and most widely used topical depigmenting
agent is hydroquinone (HQ), a structural analog of
melanin precursors that inhibits the conversion of L-3,4-
dihydroxyphenylalanine (L-DOPA) to melanin by tyrosinase.
Adverse cutaneous effects include irritation, allergic contact dermatitis, and rarely ochronosis. Multiple studies have shown that the depigmenting effect is augmented when combined with a retinoid and a corticosteroid.3,11-13 A triple combination cream of HQ 4%, fluocinolone acetonide 0.01%, and tretinoin 0.05%(Tri-Luma®) is the most widely used, although many compounded variants are used in clinical practice today. To prevent long-term sequela such as ochronosis from HQ products, it is suggested that practitioners limit treatment to 3-6 months continuously and then take a HQ "holiday."14 However, shortterm continuous therapy with long-term "weekend only" or "3 times weekly" maintenance therapy has substantial benefit for treating both melasma and PIH with very few complications. Concerns over cutaneous carcinogenesis have not been confirmed in clinical practice and are not a concern to these authors when topical HQ products are used as described above (Figure 3).
A number of HQ alternative (tyrosinase inhibition) products have flooded the market due to a demand for ingredients with less irritation and less stigma (i.e., ochronosis and carcinogenesis) than HQ. AzA, tranexamic acid, resorcinol, mequinol, and kojic acid are common constituents, often as part of a combination of agents used for lightening.18-22 AzA has intrinsic antityrosinase activity, but also acts as an anti-inflammatory agent.15 Tranexamic acid is a plasmin and prostaglandin inhibitor that leads to reduced tyrosinase activity.23 Kojic acid, a naturally derived fungal metabolite, is a potent antioxidant and has been used in combination therapy with good success given its ability to enhance epidermal penetration of other medications through improved cell turnover.
Botanicals and Cosmeceuticals
Botanically derived antioxidants and natural extracts are frequently used for skin lightening due to their skin brightening and anti-inflammatory effects (Table 2). Silymarin, arbutin, resveratrol, Aloe vera, pycnogenol, Boswellia, aloesin, niacinamide, ascorbic acid, and extracts of coffeeberry, soy, green tea, orchids, grape seed, marine algae, and licorice are some of the more common agents seen in cosmeceutical products.3,24 Arbutin, a derivative of hydroquinone derived from plants, inhibits melanosome maturation and tyrosinase activity and is one of the most widely used skin-lightening agents worldwide.16 Niacinamide (vitamin B3) interferes with the interaction between keratinocytes and melanocytes by modulating the proteaseactivated receptor (PAR-2) that is involved in melanosome transfer.25 Ascorbic acid is a natural antioxidant that interacts with copper ions in the tyrosinase active site and acts as a reducing agent in various steps of melanogenesis to inhibit pigment formation.16 Coffeeberry is another antioxidant whose effects of depigmentation have not yet been adequately studied but has been found to be helpful as an alternative treatment of melasma.16 Soy's skin lightening effects are mediated by PAR-2 and DOPA oxidase inhibition.
SkinCeuticals® Advanced Pigment Corrector, composed of a proprietary combination of a synthetic tyrosinase inhibitor (hydroxyphenoxy propionic acid), a flavonoid antioxidant (0.5% ellagic acid), 5% yeast extract, and 0.3% salicylic acid, showed similar results in terms of skin tone, spot intensity, spot size, and hyperpigmentation in a 12 week study compared to combination 4% HQ and 0.025% tretinoin cream.26 The SkinCeuticals® formulation had significantly less adverse effects such as irritability.
SkinMedica® Lytera® Skin Brightening Complex is a combination of tetrahexyldecyl ascorbate (vitamin C), niacinamide (vitamin B3), ethyl linoleate (essential fatty acid) and squalene (lipid), retinol, Dunaliella salina extract (carotenoids of phytoene and phytofluene extracted from unicellular algae), hexylresorcinol, tetrapeptide-30 (skin brightening peptide), 4-ethoxybenzaldehyde, and Glycyrrhiza glabra (licorice) root extract (rich in glabridin, an antioxidant). This unique proprietary combination of ingredients work together to brighten and even skin tone and texture, improve luminosity, and reduce the appearance of dark spots through inhibition of tyrosinase, increasing keratinocyte turnover, improving the natural skin barrier (lipid), and decreasing inflammation (antioxidants). A split face study of 68 Caucasian women with moderate to severe facial hyperpigmentation with different dose formulations of Lytera® Skin Brightening Complex versus 4% hydroquinone showed the highest patient satisfaction with Lytera® and the lowest with 4% hydroquinone. All subjects achieved a significant reduction in overall hyperpigmentation.27
Elure® Advanced Skin Brightening Technology has a natural enzyme formulation Melanozyme® that is mushroom-derived (ligninase) and a natural inhibitor of tyrosinase. In a randomized, double-blind, placebo-controlled, split-face, single-center study of 51 patients, twice daily application of this enzyme on one-half of the face led to a mean 7.6% improvement in pigmentation as measured by Mexameter® (to asses melanin and erythema values) after 31 days. The other half of the face was randomized to receive either 2% hydroquinone or placebo and did not result in a statistically significant lightening effect.28
Melaplex® is a patented combination of disodium glycerophosphate, L-leucine, phenylethyl resorcinol, and undecylenoyl phenylalanine. Both the biosynthesis of melanin (tyrosinase inhibition) as well as the transfer of melanosomes to keratinocytes is inhibited (by decreasing the supply of L-tyrosine).29-30
Chemical peels are frequently reported in the literature as
effective for the treatment of hyperpigmentation such as
melasma.3,31 Superficial peels such as salicylic acid, Jessner's solution (salicylic acid and lactic acid with resorcinol) and glycolic acid are reported to provide improvement with the least risk of complications. Stronger peeling agents such as multiple pass Jessners, Jessner's/trichloroacetic acid (TCA) combination,
TCA 35% or phenol, induce much more inflammation and the
potential to significantly worsen pigmentation. It is the author's preference (JE) to limit chemical peeling agents for the treatment of hyperpigmentation with the exception of salicylic acid (or lowdose combination peels, see below) due to the intrinsic ability for this agent to decrease inflammation, which is a reason it functions well as a peeling agent in other skin conditions like rosacea.
Intense Pulsed Light
Intense pulsed light (IPL) is not considered a first-line treatment for melasma or PIH.1 Initial studies for the treatment of melasma showed improvement compared to control, but results were rarely sustained and, in some instances, showed the condition worsening.32 Results were improved if topical triple therapy was combined with IPL treatments, as compared with triple therapy alone.33-34 Although there are some studies documenting improvement in PIH with IPL, it is not a standard therapy as one of the more common complications from IPL treatment, even when well performed, is post-inflammatory dyschromia.35 Moreover, IPL is not ideal for Fitzpatrick skin types 4 to 6, comprising the more common population of patients with melasma and PIH. IPL for pigmentation should be considered as a last resort therapy employing very conservative treatment parameters, and administered through a series of sessions combined with an appropriate lightening skin care regimen and sun protection.
LasersAlthough lasers are reported in many studies to be helpful for the treatment of melasma (and in some instances PIH), in reality, there is a significant limitation to laser-based devices for pigmentation given the risk of rebound pigmentation or worsening, even with conservative treatment.3,11 Theoretically, selective photothermolysis of melanosomes should induce destruction of excessive pigmentation, but any irritation or inflammation has the ability to induce reactive melanocytosis and, thus, worsen pigmentation.36 In addition, post-procedural photosensitivity (along with hormonal induced photosensitivity seen in melasma) poses a major problem for long-term maintenance of results without an intensive brightening, anti-inflammatory, and sun-protective skin care regimen. Fitzpatrick skin types 4 to 6 can rarely be treated with energy-based devices due to the risk of PIH. Shortening the pulse duration (less than the 50 to 500 nanosecond thermal relaxation time of melanosomes) allows for more specific pigment targeting with less thermal byproduct.2,3 By quickly pulsing the energy, you can obtain a high peak power and generate high local temperature gradients between melanosomes and the surrounding structures. Further shortening (to picosecond and beyond) adds a high-pressure photoacoustic effect that decreases the thermal consequence on surrounding structures and increases pigment removal through physical disruption of the involved melanosomes.11,37-38
Common theory is that longer wavelengths (e.g., 1064 nm, Q-switched neodymium-doped yttrium aluminum garnet [Nd:YAG]) penetrate deeper but also spare the epidermis (normal melanin), making it safer to treat darker skin types and deep dermal pigmentation. Q-switched ruby (694 nm) lasers, although beneficial for pigmentation due to their high reactivity on melanin, can induce permanent hypopigmentation if conservative settings on patients with the appropriate skin type are not followed. Studies have shown improvement in a variety of pigmented conditions treated with longer-wavelength lasers such as ephelides, nevus of Ota, and tattoos.39 As with any laser, dyspigmentation, acneiform eruptions, petechiae and herpes simplex re-activation are risks. Combination treatment with topical brightening agents (e.g., hydroquinone, triple cream, arbutin, vitamin C, and AzA) and other cosmetic procedures described above (e.g., chemical peels) may enhance outcomes.11,40
One author's go-to standard treatment is low-energy, low-density 1440 nm fractional diode laser (Clear + Brilliant® Laser System) as it can treat pigmentation with little downtime or risk of PIH due to the low energy/density settings and improvements occurring slowly over time (Figure 4). Additionally, there are several studies that have shown benefit of the 1927 nm thulium fiber laser of the Fraxel® re:store Dual, FDA approved in 2009 for the treatment of melasma and pigmented lesions.41-43 Previously, this author utilized the 1927 nm thulium fiber laser (Fraxel® re:store Dual) for melasma due to its shallow penetration (200 µm depth as compared to 400-1500 µm depth of the 1550 nm erbium (Er):YAG). However, after having frequent cases of worsening or rebound, he switched to utilizing low-fluence, lowdensity treatments alone or in combination with salicylic acid peels, microneedling, or spot liquid nitrogen treatment, which ultimately gave much better initial and long-term outcomes. Additionally, melasma, and sometimes PIH (although seen more with poikiloderma than PIH), has a vascular component that needs treatment with either a pulsed dye laser (585 nm) or potassium titanyl phosphate (KTP) laser (532 nm) to improve the overall texture and tone. More studies are needed on combination treatments for melasma and PIH, as in clinical practice multiple modalities with strict topical skin care regimens are being used to give the best results with long-term outcomes (Table 3).
Lastly, although reported in the literature as effective, ablative lasers (Er:YAG 2940 nm or carbon dioxide [CO2] 10600 nm) should never be used for melasma or PIH due to the very high potential of worsening hyperpigmentation.
Radiofrequencey (RF) technology has more recently become
widely used in cosmetic medicine as a result of its efficacy and safety in a variety of aesthetic conditions including melasma. RF devices produce electrical current using electromagnetic radiation in the frequency range of 3 kHz to 300 MHz.44 When the current is applied to tissue, the resistance (impedance) produces heat that induces dermal neocollagenesis. Fractional RF devices
produce low-density ablation with deep penetrating energy,
giving these devices the ability to improve texture, tone and color in all skin types, while also improving wrinkles, acne scars, and laxity. Since melanin is not a target of the device, there is little to no risk of hyperpigmentation unless multiple pass treatments are used with fractional devices, thereby inducing too high levels of
ablation (Figure 5).
Melasma and PIH are cosmetically disturbing to patients and frustrating to physicians performing procedures, as there is currently no best single therapy that gives significant short and long-term results. Combination therapies have the potential to improve results, but long-term maintenance treatments are needed for optimal outcomes. Future direction of studies are focusing on "color blind" technologies that can treat all skin types and multiple cutaneous concerns. It is important that physicians be knowledgeable about the most current therapies such as picosecond lasers, low-fluence/low-density non-ablative lasers, fractional radiofrequency, and microneedling in order to enhance patient results and limit complications.
Figure 1a. Dyschromia from IPL on a patient with skin type 4 who was not an appropriate candidate for this treatment. Notice the broad areas of hyper and hypopigmentation.
Figure 1b. Melasma. Hyperpigmented patches in the classicdistribution of the face of a female with worsening skin complaints despite topical hydroquinone and sunscreen.
Figure 2. PIH. Linear hyperpigmented streaks and residual erythema in a patient 3 weeks after full face erbium laser resurfacing.
Figure 3. Improvement in melasma after 6 weeks of twice daily topical triple therapy and 2 treatments of full-face 20% salicylic acid peels. Results are often subtle, as seen here, and require a series of treatments to achieve significant improvements.
Figure 4. Combination treatment. Significant improvement in melasma with a combination of low-level/low-density nonablative laser (Clear + Brilliant®, 3 treatments 3 weeks apart), topical lightening skin care with a vitamin C antioxidant (CE Ferulic, SkinCeuticals®) and kojic acid (Phyto +, SkinCeuticals®) in the morning and hydroquinone and tretinoin 0.025% cream at night, and full-face 20% salicylic acid peels weekly.
Figure 5. Fractional radiofrequency (RF). Improvement in dyschromia is seen after 3 fractional RF treatments spaced 3 weeks apart (Venus Viva™, 230 volts, 10-20 msec, single pass per treatment). Note the additional improvement in acne scarring and pores.
In this issue:
All content ©2004-2017 SkinTherapyLetter® |
Last modified: Thursday, 07-Jan-2016 10:52:10 MST