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Cosmetic Approach for Melasma

Ana Carolina Handel, Luciane Donida Bartoli Miot, and HélioAmante Miot

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Physiopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Clinical Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Diagnostic Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Impact in the Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . 4

Treatment of Melasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Photoprotection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Topical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Oral Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Peelings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Light-Related Technologies . . . . . . . . . . . . . . . . . . . . . . . . . 8

Other Surgical Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Take-Home Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

AbstractMelasma is a chronic acquired focal hyper-melanosis localized on sun-exposed areas thatcommonly affects females during their fertileyears. Despite many known risk factors ascumulative sun exposure, oral contraceptivepills, pregnancy, stress, cosmetics, and somedrugs, the physiopathology of melasma is notyet fully understood, which limits the develop-ment of definitive treatments and preventionstrategies. Family occurrence (40–60%) is anevidence of genetic predisposition. Here, wediscuss the role of sun protection, topicalbleachers, light technologies, peelings, andoral strategies on therapeutic approach ofmelasma. Moreover, prognostic factors arepointed out.

KeywordsMelasma • Melanosis • Contraceptives • Oralcontraceptives • Pregnancy • Hormones •Chloasma • Gonadal steroid hormones •Melanosis • Pigmentation • Skin pigmentation• Ultraviolet rays • Pigmentation disorders

Introduction

Melasma is a chronic and acquired localizedhypermelanosis, which affects mainly women ofintermediate phototypes during fertile age (Miotet al. 2009).

A.C. Handel (*) • L.D.B. Miot • H.A. MiotUnesp, Botucatu, SP, Brazile-mail: [email protected]; [email protected]; [email protected]

# Springer International Publishing AG 2017M.C.A. Issa, B. Tamura (eds.), Daily Routine in Cosmetic Dermatology, Clinical Approaches and Proceduresin Cosmetic Dermatology 1, DOI 10.1007/978-3-319-20250-1_25-2

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It is characterized by symmetrical brownishmacules with irregular edges and well-definedcontours, mainly on the zygomatic, frontal,upper lip, nose, and chin. Less often, it affectsextrafacial areas like the neck, arms, and anteriorchest (Tamega Ade et al. 2013).

Melasma is a common disease in dermatolog-ical practice. In a Brazilian dermatologic survey,pigmentary diseases were the main cause ofsearch for dermatologic care (Lupi et al. 2010).Studies in Nepal and Saudi Arabia indicatemelasma as the fourth most frequent diagnosis(Alakloby 2005; Walker et al. 2008).

It occurs in all ethnic and population groups;however, epidemiological studies have reportedhigher prevalence among more pigmented pheno-types, such as East Asian, Japanese, Korean andChinese, Indian, Pakistani, Middle Eastern, andAfrican peoples. In the Americas, it is commonamong Hispanics and Brazilians who inhabit trop-ical areas, where there is increased chronic expo-sure to ultraviolet radiation (Handel et al. 2014b).

Although it can affect both sexes, melasmaoccurs more often in women in a ratio of 9–10:1.An Indian study identified a less impressive ratio(6:1); already in Brazil and Singapore, there weremost notable predominance, 39:1 and 21:1 (Acharand Rathi 2011; Goh and Dlova 1999; Hexselet al. 2014).

Among men, sexual steroids are not involvedin most cases, but the report of intense sun expo-sure is imputed as main trigger factor. There is noclinical or histopathological characteristic thatleads to consider as a different disease thanmelasma in women (Sarkar et al. 2010;Vachiramon et al. 2012; Vazquez et al. 1988).

There is no consensus on the clinical classifi-cation of melasma; most authors divide it ascentrofacial and peripheral. The centrofacial typeincludes the cases that lesions are predominant inthe center of the face or front, glabellar, nasal,zygomatic, upper lip, and chin. The peripheralmelasma corresponds to impairment offrontoparietal regions, pre headset, and along thebranches of the mandibulae (Tamega Ade et al.2013).

There are several factors involved in the devel-opment of melasma, such as sun exposure, preg-nancy, oral contraceptives and other steroids,ovarian tumors, hormone replacement therapy,cosmetics, photosensitizing drugs, inflammation,and stressful events. In addition, genetic predis-position is suggested by high familial incidencereports (40–60%). This evidences that melasma isa multifactorial disease and depends on the inter-action of environmental and hormonal elementswithin a susceptible genetic substrate (Handelet al. 2014a).

Sun exposure is the main risk factor formelasma, exerting role both in its appearance asin worsening and maintenance. There is a clearimprovement of melasma in the winter monthsand the aggravation in the summer periods andintense sun exposure. Moreover, the use of high-spectrum sunscreen reduces disease severity by50% and decreases its effect on pregnancy inmore than 90 % (Lakhdar et al. 2007; Miot andMiot 2009).

In a Brazilian study with 302 patients withfacial melasma, 48.5% reported intense sun expo-sure as a trigger. Another study showed that resi-dents of rural and coastal areas had a higherfrequency of facial melasma, evidencing the roleof chronic sun exposure in disease development(Handel et al. 2014a; Tamega Ade et al. 2013).

Physiopathology

The physiopathology of melasma is not yet fullyunderstood. Compared with the adjacent epithe-lium, there is greater melanin synthesis withhigher yields and more mature melanosome trans-fer for all layers of the epidermis (Miot et al.2010).

Melanocytes are hypertrophied with dendritesand most prominent organelles. Keratinocytesalso express phenotypic changes such as changesin chromatin and organelles. This suggests that thepathophysiological process involves not only themelanocytic hypertrophy but the wholeepidermal-melanin unit (Brianezi et al. 2015).

2 A.C. Handel et al.

There are some alterations in the upper dermissuch as collagen degradation; solar elastosis; dam-age in the basal membrane; presence ofmastocytes, CD4+ lymphocytes, and CD68+ mac-rophages; and activity of MMP1, MMP2, MMP3,and MMP9. These findings suggest that a chronicinflammatory process can stimulate and maintainmelanogenesis independently of sun exposure, asoccurs in post-inflammatory pigmentation (Kang2012; Passeron 2013; Rodriguez-Arambula et al.2015).

Some inflammatory mediators are hyper-expressed in melasma skin as endothelin, iNOS,IL17, NF-Kβ, and COX-2, and those are thoughtto provide an oxidative and inflammatory micro-environment that can lead to chronic pigmenta-tion. Moreover, growth factors as stem cell factor,αMSH, hepatocyte growth factor, b-fibroblastgrowth factor, nerve growth factor, and VGEFinfluenced directly melanin production and areexpressed prominently in melasma skin (Passeron2013; Samaka et al. 2014).

The reason why all these alterations occur inmelasma but not in adjacent skin that has similar –or even greater – sun exposure regimen through-out life is the key to understand disease pathogen-esis and elaborate prevention and managementstrategies.

Clinical Manifestations

Melasma is characterized by brownish maculeswith sharp limits and irregular contours. It affectssun-exposed areas, especially the face and neckand less frequently in the arms and sternum (Han-del et al. 2014b; Tamega Ade et al. 2013).

According to the clinical distribution, melasmacan be classified into centrofacial and peripheral(Fig. 1). The centrofacial lesions are the mostcommon and affect the glabellar region, frontal,zygomatic, nasal, upper lip, and chin. Peripheralmelasma occurs at the frontoparietal and temporalregions, preauricular over the mandibular rami(Sheth and Pandya 2011).

In Brazil, centrofacial melasma occurs in 52%of women, but 43% have mixed regions affected(Tamega Ade et al. 2013). In Tunisia, anothersurvey with 188 women disclosed 76% melasmacentrofacial and 22% mixed (Guinot et al. 2010).

The exclusively mandibular melasma is rareand may represent a form of poikiloderma ofCivatte, because patients are often postmeno-pausal and analysis of skin biopsies identifiessignificant actinic damage (Guinot et al. 2010;Mandry Pagan and Sanchez 2000). Studies haveshown a low incidence of exclusively peripheral

Fig. 1 Melasma.Predominantly centrofacial(a): zygoma, labial superiorfrontal, and glabella.Predominantly peripheral(b): frontoparietal,temporal, parotid, andmandibular rami

Cosmetic Approach for Melasma 3

melasma. A Brazilian survey with 302 women hasidentified only two exclusively mandibularmelasma, and 65% of them have also parotideallesions (Tamega Ade et al. 2013). To reinforcethese results, an Indian study disclosed just 1.6%of exclusively mandibular melasma among312 women (Achar and Rathi 2011).

The most affected site is zygoma, followed bysupralabial, frontal, nose, temporal, and chin(Handel et al. 2014a; Tamega Ade et al. 2013).

Although less common, other sites may beinvolved, such as the forearms and upper arms,neck, back, and sternum, characterizing themelasma extrafacial that can be associated withany of the other facial patterns. Generally,melasma affecting the upper limbs is related toolder women, menopause, and use of hormonereplacement therapy (O’Brien et al. 1997). Histo-pathological examination revealed a similar pat-tern to that described for facial melasma;furthermore there is no epidemiological character-istics that lead to the conclusion that extrafacialmelasma composed an independent disease(Ritter et al. 2013).

Diagnostic Tests

The diagnosis is essentially clinical melasma.However, there are some resources to aid thedermatologist in the differential diagnosis.

The Wood’s lamp produces a light irradiationwith wavelength of 340–400 nm; density anddepth of melanin pigment determine the attenua-tion of fluorescence. The equipment highlights theskin pigmentation difference, and melasma lessintense the light of Wood respond better to topicaltreatments (Ponzio and Cruz 1993).

Under dermatoscopy, the color of melanindepends upon the quantity and level of location,ranging from black when in the stratum corneumto brown in the lower layers of the epidermis tothe blue or blue-gray in the dermis. The methodalso allows the identification of vascular lesions insome part of melasma (Stolz et al. 2003; Weis-mann and Lorentzen 2006).

Histopathologically, melasma is characterizedby epidermal hyperpigmentation without

increasing the number of melanocytes, but theseare hypertrophied and hyperfunctioning withlarger dendrites and cytoplasmic organelles,showing high metabolic activity. There is anincreased amount of melanin in all layers of theepidermis, an increased number of mature mela-nosomes. There is a clear damage in collagen IVfrom basal membrane (lamina densa), what leadsto a phenomena called pendulous melanocytes(Fig. 2). At the dermis, there is abundant elastosis,and mast cells are the predominant inflammatorycells. The dermal pigmentation does not differbetween the skin with melasma and the adjacenthealthy skin (Kang et al. 2002; Miot et al. 2010;Shin and Kang 2006; Torres-Alvarez et al. 2011).

The most important differential diagnoses aresolar lentigines, toxic melanoderma, Riehl’smelanosis, post-inflammatory pigmentation, fric-tion melanosis, ochronosis (endogenous andexogenous), cutaneous lupus erythematosus,actinic lichen planus, acanthosis nigricans, drug-induced pigmentation (e.g., amiodarone), Brocq’serythrosis peribuccalis, periorbital pigmentation,pellagra, café-au-lait macules, facialerythomelanosis follicular, photodermatitis, andOta’s nevus (Kang et al. 2002; Pandya and Gue-vara 2000; Sheth and Pandya 2011).

These diseases can coexist in patients withmelasma; differential diagnosis is important forproper treatment planning.

Impact in the Quality of Life

Melasma is a cause of emotional stress and embar-rassment that influences the quality of life ofpatients. Many report feelings of shame and lowself-esteem, affecting your everyday life (Freitaget al. 2008).

MELASQol (Melasma Quality of Life Scale)is a questionnaire that evaluates the effects ofmelasma in the emotional state, social relation-ships, and daily activities of patients. This ques-tionnaire consists of ten items, scored 1–7, beingthe highest score indicative of a poorer quality oflife. MELASQol has been validated for differentcountries, including Brazil (MELASQol-BP)(Balkrishnan et al. 2003; Cestari et al. 2006b).


There is poor correlation between theMELASQol and the severity of the disease esti-mated by MASI score (Melasma Area and Sever-ity Index), suggesting that the subjectiveperception of the patient exceeds the dimensionof the clinical dyschromia (Cestari et al. 2006a;Freitag et al. 2008).

MELASQol also reveals that patients with alower educational level, with moderate depression

and anxiety, have a higher degree of emotionalimpact (Freitag et al. 2008).

Despite melasma not considered a serious dis-ease at a clinical perspective, patients reportstrong emotional embarrassment and concern. Itis necessary to assess individual needs and moresatisfactory treatment opportunities facing theindividuality of each patient (Freitag et al. 2008;Rendon 2004).

Fig. 2 Histopathology of melasma. a Fontana-Masson evidenced melanin overproduction in all epidermal layers – 40�.b Melan-A and PAS showing pendulous melanocytes (into the dermis) and the damage of basement membrane – 100�


Treatment of Melasma

Best treatment strategy in melasma comprises therecognition of factors of impairment of the lesionsas daily sun exposure, phototoxic drugs, cos-metics, skin picking (lead to post-inflammatorypigmentation), adhesion to the treatment, and hor-monal steroids (e.g., contraceptive pills or hor-mone replacement therapy). Efforts should bemade for the prompt interruption of these factors.

Preventive measures, as rigorous sun protec-tion and quitting hormonal steroid supplementa-tion, should be indicated to all high-risk patientsas pregnant women and first-degree relatives frompatients with melasma.

Despite the frequency of the disease, there arestill few randomized controlled trials to investi-gate treatment strategies on melasma. Treatmentslisted below are – in most part – evidenced by caseseries with short follow-ups.

To date, there is no curative treatment ofmelasma. Most strategies lead to the inhibitionof tyrosinase, act as anti-inflammatory or anti-oxidative agents, try to remove pigments fromepidermis, and strengthen photoprotection mea-sures. While we do not understand theetiopathogenesis of melasma, treatments are con-ceived just to minimize its consequences.

Photoprotection

Sunscreens with large wavelength protection(UVA and UVB) are indicated for the preventionand as part of the treatment of melasma (Abarcaet al. 1987; Miot and Miot 2009; Rendon 2004).Potent sunscreens (SPF >50 and PPD >20) arerecommended to compensate insufficient amountof the substance and lack of periodic reapplication(Schalka et al. 2009).

Despite lack of evidence about the role ofvisible light in melasma, tinted sunscreens arerecommended for women, as warrant more homo-geneous spreading. Most studies include longer-wavelength UVA to the analysis of visible lighteffects, and it can be misleading regarding thepositive effect against visible light protection or

just larger UVA protection (Castanedo-Cazareset al. 2014; Mahmoud et al. 2010).

Moreover, iron (ferric) oxide, present in mosttinted sunscreen, is an important antioxidant com-pound, and its activity increases as the substanceis micronized. Since melanogenesis is an oxida-tive process and there are an oxidative stress inmelasma due to chronic inflammation, the effectof ferric oxide also can be misunderstood as vis-ible light protector but a potent antioxidant(Castanedo-Cazares et al. 2014; Paul et al. 2009;Seckin et al. 2014).

Skin heating due to solar infrared radiation isanother factor that can lead to impair melasmalesions. Heat-shock proteins can activate MMP1,MMP3, and MMP9 in the upper dermis that pro-vide degradation of collagen and elastic fibers. Todate, there is no sunscreen that effectively blocksinfrared radiation, but exposure to heat (e.g., into acar, work in front of ovens) should be avoided(Breathnach 1996).

Physical measures of sun protection (e.g., hat,umbrella, vehicular glass film) and looking forshadows are other recommendations in order tominimize solar incidence in melasma.

Topical Agents

Most topical agents are indicated to tyrosinaseinhibition, as anti-inflammatory or topical antiox-idants. There are few comparative studies in vivothat evaluate different drugs, concentrations, com-position, and tolerability. Main topical strategieson melasma are listed below:

Alpha-arbutin – This is a stable derivative ofhydroquinone but less irritating; it blocks theepidermal synthesis of melanin by inhibitingtyrosinase and is more potent than kojic acid.Concentration: 1–6%.

Symwhite – It is a resorcinol derivative and apotent inhibitor of tyrosinase with antioxidantaction. Safe, stable, effective, and non-cytotoxic and can be used in eastern skin. Con-centration 0.1–0.5%.

Azelaic acid – It is a carboxylic acid synthesizedby Malassezia furfur, which competes with


tyrosinase inhibiting its activity. Its action isalso antioxidant, anti-inflammatory, and anti-bacterial. Concentration: 15–20% in two appli-cations a day (Cestari et al. 2009; Nazzaro-Porro and Passi 1978).

Kojic acid – Derived from Aspergillus oryzae,inhibits tyrosinase, induces reduction ofeumelanin. Best action when combined with5% glycolic acid. Concentration: 0.5–6 %(Garcia and Fulton 1996). As an ester(dipalmitate) it increases tyrosinase inhibition.

Tranexamic acid – It blocks melanin synthesis inmelanocytes by interfering with the interactionof keratinocytes and melanocytes by inhibitingplasmin-plasminogen system (present in theepidermal basal cells). Concentration:0.4–3%. Nevertheless, it is more effectivewhen administered orally (see below) (Steineret al. 2009).

Cysteamine (cloridrato 2-mercaptoethylamine) –Thiol compound that inhibits tyrosinase andperoxidase. Concentration: 5% in cream.

Corticosteroids – Potent corticosteroids decreasemelanin synthesis and skin metabolism leadingto the improvement of melasma. They can beused alone (e.g., clobetasol 0.05%) or in com-bination with other agents (e.g., triple associa-tion: fluocinolone, tretinoin, andhydroquinone). Skin atrophy, striae distensae,and telangiectasies are the major concern asso-ciated with long-term use (Kligman and Willis1975).

Hydroquinone – It is an aromatic organic com-pound from the group of the phenols being themost potent blocker of melanin synthesis byinhibiting tyrosinase, preventing the conver-sion of DOPA to melanin. It is considered thegold standard as depigmentation agent. Con-centration 2–4% (higher concentrations areassociated with increased incidence of exoge-nous ochronosis) (Kramer et al. 2000; Rendonet al. 2006; Rendon 2004).

Methimazole – It is an antithyroid medication,potent inhibitor of tyrosinase and peroxidase.Serum levels are not detected if applied in anarea up to 50 cm2. Concentration: 5 % (Maleket al. 2013).

Tretinoin – It is a tyrosinase inhibitor retinoid andcan also remove pigment granules ofkeratinocytes and accelerate epidermal turn-over. Other retinoids used in melasma includeisotretinoin, adapalene, and tazarotene. Theassociation with other agents (e.g., hydroqui-none and fluocinolone) improves its effects.Concentration: 0,025–0,05 % (Dogra et al.2002; Griffiths et al. 1993; Gupta et al. 2006;Kimbrough-Green et al. 1994; Leenutaphonget al. 1999; Rendon et al. 2006; Rendon 2004).

Vitamin C – Ascorbic acid inhibits the action oftyrosinase in addition to having antioxidantaction; however, their effectiveness is limitedby chemical instability. Concentration:5–20 % (Huh et al. 2003; Taylor et al. 2013).

Triple combination and Kligman’s formulae –The combination of hydroquinone, tretinoin,and fluocinolone is the first-choice treatmentof melasma and characterizes the most potentstrategy to improve melasma and long-termmaintenance of the results. There are severalrandomized controlled studies disclosingfavorable outcomes for this strategy with sun-screen alone or in combination to chemicalpeels and tranexamic acid (Arellano et al.2012; Chan et al. 2008; Godse and Sakhia2011; Padhi and Pradhan 2015).

Flavonoids, ellagic acid, soya, alpha-lipoicacid, idebenone, phytic acid, and green tea,among others, are used as adjuvants of traditionaldepigmenting agents (Sarkar et al. 2012b). None-theless, there are few controlled studies regardingefficacy and tolerability of these agents in thetreatment of melasma.

Oral Agents

Tranexamic acid – Blocks the conversion ofplasminogen to plasmin, through the inhibitionof the activator of plasminogen, the main proteasein epidermis. This results in less free arachidonicacid and a decreased ability to produce prosta-glandins that activate tyrosinase. Originallytranexamic acid is prescribed as a pro-thrombotic


agent and should be avoided in high-risk patients(e.g., post-thrombotic, smoking, oral hormonalcontraceptive, antiphospholipid syndrome) orwho need anticoagulation. Oral administrationdisclosed superior results to topical andintralesional injection for melasma bleaching andshould be used as an adjuvant to depigmentingagents as triple association. The usual dosage is250 mg 12/12 h by 3–6 months. The adverseeffects were uncommon, but reduction of men-strual flow and gastrointestinal discomfort is themost commonly reported (Budamakuntla et al.2013; Cho et al. 2013; Karn et al. 2012; Li et al.2014; Na et al. 2013; Padhi and Pradhan 2015;Shin et al. 2013; Wu et al. 2012).

Pycnogenol (Pinus pinaster) – It is derivedfrom a French maritime pine rich in flavonoids.It contains potent anti-inflammatory and antioxi-dant properties. The usual dosage is 75–100 mg/day divided in two to three doses by 2–4 months(Kim et al. 2008; Ni et al. 2002).

Polypodium Leucotomos – It is a tropicalbracken native of South and Central America,rich in phenolic derivatives. It has aimmunomodulator, antioxidant, and anti-inflam-matory properties. The oral administrationreduces the sun-induced erythema and pigmenta-tion. These findings indicate it as an adjuvant totopical photoprotection, and also it was shown toreduce pigmentation of melasma. The usual dos-age is 250–500 mg/12/12 h by 2–4 months(Ahmed et al. 2013; Middelkamp-Hup et al.2004; Nestor et al. 2014).

Despite reports of success, there are still fewrandomized and controlled studies to understandand support the role of oral antioxidants inmelasma, neither the comparison of poweramong them nor different regimens of treatment.

Peelings

Most chemical peels used in the treatment ofmelasma are aimed to desquamate stratumcorneum and remove the excess of melanin.They are effective adjuvants in clinical treatmentof melasma, accelerating the clinical results(Rendon et al. 2008).

Deeper peelings are matter of concern inmelasma since the inflammatory process canlead to melasma rebound and post-inflammatoryhyperpigmentation.

Glycolic acid – alpha-hydroxy acid derivatefrom sugar cane. Peelings should be performedeach 2–4 weeks. Concentration: 30–70 % (Godseand Sakhia 2011; Hurley et al. 2002; Ilknur et al.2010; Lim and Tham 1997; Sardana et al. 2013;Sarkar et al. 2002, 2012a).

Jessner’s solution – Combination of resor-cinol (14%), salicylic acid (14%), and lactic acid(14%). There are several reports of its efficacy inthe treatment of melasma as adjuvant to clinicaltherapy (Ejaz et al. 2008; Lawrence et al. 1997;Sarkar et al. 2012a; Sharquie et al. 2006).

Tretinoin peel – as effective as Jessner’s solu-tion or glycolic peel 70% in the treatment ofmelasma. Concentration: 1–5 % (Khunger et al.2004).

Salicylic acid – as effective as Jessner’s solu-tion in the treatment of melasma, especiallyamong darker patients. Concentration: 30 %(Ejaz et al. 2008).

Trichloroacetic acid (10–30%) and lactic acid(92%, pH 3.5) are reported as effective in theadjuvant treatment of melanoma but did not accu-mulate evidence that proves them superior to theprevious peelings (Nanda et al. 2004; Sharquieet al. 2006).

Light-Related Technologies

Most light technologies involve lasers and intensepulsed light; nevertheless there are several equip-ments and regimens of use (e.g., fluence, filters,pulse duration, energy, and wavelength) that dif-ficult the comparison of the results among them aswell as the reproducibility of the outcomes.

Intense pulsed light (IPL) – It is a non-coherent light source, with filters between500 and 1,200 nm. IPL has affinity for melaninand hemoglobin. There are over 20 different typesof IPL equipment in the world, but commonlyfilters of 500–550 nm are the most reported inthe treatment of melasma. It is an alternative forthose patients refractory to other treatments. Care


should be taken to not trigger the rebound phe-nomenon or provoke post-inflammatory hyper-pigmentation due to epidermal injury. Thedifferent studies have shown its effectiveness ifsimultaneously employed in clinical treatmentwith bleachers but did not undergo long-termfollow-up (>1 year). In addition, there are reportsof facial melasma aroused after IPL for photoag-ing, warning that the epidermal heating can triggersubclinical melasma. In patients with importantvascular component, IPL can contribute in thisspecific treatment (Chan and Kono 2004; Chunget al. 2014; Moreno Arias and Ferrando 2001; Naet al. 2012; Negishi et al. 2004; Wang et al. 2004;Zaleski et al. 2012; Zoccali et al. 2010).

LASERS – The use of laser for treatment ofpigmentary disorders is based on the theory ofselective photothermolysis, which proposes a spe-cific spectrum of light emitted by a specific laserthat is selectively absorbed by a cell type or tissue.Short and selective pulses to selective pigmentscan cause physical damage to the pigmentarystructures (Goldberg 1997). Similar to the chem-ical peeling, lasers have an increased risk of sideeffects by direct damage to the skin, whichbecomes more prevalent in patients with higherphototype. The following technologies haveachieved some benefits in the treatment ofmelasma.

Nonablative fractional laser – Erbium1,550 nm. It provides a melanin and melanocytereduction in melasma. Best results are obtained infair skin patients after four monthly sessions.There is up to 20% of improvement, but therelapses are very common along the time (65 %)(Goldberg et al. 2008; Lee et al. 2009; Naito2007).

Nonablative fractional laser – Thulium1,927 nm. This wavelength has a higher wateraffinity than the 1,550 nm, providing less epider-mal injury (Ho et al. 2013; Polder and Bruce2012).

Q-switched neodymium-doped yttrium alu-minum garnet (QS-Nd:YAG�1,064 nm) – It hasa best affinity for the melanin than the previouslasers. As adjuvant to photoprotection and topicalbleachings, five sessions (low fluence) weekly canreduce melasma pigmentation. The main concern

resides in post-inflammatory hyperpigmentationor hypochromia due to epidermal injury andrelapse of melasma in 12 weeks in all patients(Park et al. 2011; Wattanakrai et al. 2010).

Pulsed dye laser (PDL) – This is a laser withhigh affinity for hemoglobin and indicated for thetreatment of vascular component of melasma. Theuse of up to three applications every 4 weeks,concurrently with the depigmenting clinical ther-apy, promotes improvement of melasma that wasmaintained for more than 8 weeks (Passeron et al.2011).

Ablative fractional laser – CO2 10,600 nm.Ablative fractional lasers at high risk of post-inflammatory hyperpigmentation and low levelof tolerance due to the intense epidermal damage.However, low-fluence fractional laser evidencedto be an adjuvant to clinical treatment of melasma,promoting higher depigmentation than clinicaltreatment alone (Rivas and Pandya 2013; Trelleset al. 2010).

Other Surgical Procedures

Dermabrasion – Since melasma does notdevelop on scars, superficial (upper dermis) derm-abrasion was considered a curative technique formelasma.

There is just one case series with 398 Thaipatients and long-term follow-up (5 years) andthe report of high rates of maintained success(Kunachak et al. 2001).

By the way, microdermabrasion was proven tobe of minimal benefits in the treatment ofmelasma; it favors the penetration of agents andpeelings (e.g., trichloroacetic acid 15 %) (Bhallaand Thami 2006; Cotellessa et al. 2003; Lee et al.2003).

Microneedling –Microneedling is a techniqueof repeated drilling of the dermis in order toinduce repair and neocollagenesis. Recently,microneedling has been used to enhance transder-mal absorption of drugs (drug delivery)(Doddaballapur 2009; Lee et al. 2014; Yoonet al. 2010).

The most widely used instrument to performthis technique consists of a polyethylene roll full


of sterile stainless steel needles symmetricallyaligned in rows for a total of 190 units on average,varying according to the manufacturer. The lengthof the needles may vary from 0.25 to 2.5 mmaccording to the model. Topical local anestheticsshould be used, and, sometimes, association withanesthetics blocks is necessary (more than 1 mmneedles) (de Andrade Lima et al. 2013; Fabbrociniet al. 2009, 2011).

A comparative study of microinjections oftranexamic acid against microneedling associatedwith the topic tranexamic acid in melasma extra-facial was performed. The group associated withthe microneedling showed superior improvementin MASI (44.4 %) (Budamakuntla et al. 2013).Another study evaluated 20 patients using depig-mentation serum isolated on a hemiface againstmicroneedling associated with depigmentationserum in the other hemiface. The hand treatedwith the combination therapy showed a statisti-cally reduced MASI, in addition to a clinicallyimportant improvement (Fabbrocini et al. 2011).

There are anecdotal reports that the isolatedmicroneedling has lightening melasma. In fact,the repair of the upper dermis and collagensynthesis-induced microneedling have the poten-tial to reverse the damage of the dermal melasma.Controlled studies should be performed to under-stand the role of microneedling (alone or as ameans of drug delivery) in the treatment ofmelasma.

Prognosis

Melasma is a chronic and relapsing diseasedespite adequate treatment. In general, treatmentresponse is better among fair skin patients, youn-ger than 35 years or older than 45 years old(Zaleski et al. 2012).

The more prominent the pigmentation, and themore extensive the disease, the less effective thetreatment response and more common therelapses, principally after sun exposure or skininjury (e.g., peelings and IPL) (Sarkar et al.2012a).

Melasma tends to fade spontaneously aftermenopause and with aging, probably due to the

decrease of hormones and gradual loss of mela-nocyte number and function in the epidermis.

Take-Home Messages

1. Melasma is a chronic and acquired localizedhypermelanosis, which affects mainly womenof intermediate phototypes during fertile age.

2. Sun exposure is the main risk factor formelasma, exerting role both in it appearanceas in worsening and maintenance.

3. The exact mechanism of skin melanogenesis inmelasma is currently not well understood.

4. The upper dermis and lamina densa damagesuggest the role of dermal injury/repair processin disease pathogenesis.

5. Regular application of broad spectrum andphysical sunscreen as well as avoidance ofultraviolet and visible light are important forpreventing recurrence.

6. Topical bleaching agents are still first line treat-ments for melasma.

7. Microneedling is a promising treatment modal-ity for melasma.

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