A focused review on acne-induced and aesthetic procedure-related postinflammatory hyperpigmentation in Asians

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1 DOI: /jdv JEADV REVIEW ARTICLE A focused review on acne-induced and aesthetic procedure-related postinflammatory hyperpigmentation in Asians S. Eimpunth, R. Wanitphadeedecha, W. Manuskiatti* Department of Dermatology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand *Correspondence: W. Manuskiatti, woraphong.man@mahidol.ac.th Abstract Postinflammatory hyperpigmentation (PIH) is a common consequence following cutaneous inflammation in darkskinned individuals with Fitzpatrick skin phototypes (SPTs) III VI. The exact pathogenesis of this condition is unknown, but is believed to be an integral part of the normal response of the skin to inflammatory stimuli. PIH can last from months to years and may significantly impair quality of life of affected individuals. The primary treatment of PIH is prevention and treatment of the underlying inflammatory condition. In addition to prevention, there are a variety of medication and procedures used to treat PIH. Although topical skin-depigmenting agents remain the treatment of choice for PIH, s and light sources may be an effective adjunctive therapy or alternative for treatment failures. When treating PIH, any treatment options selected should be optimized and utilized carefully because the treatments itself may worsen the PIH. Conflict of Interest None declared. Introduction Postinflammatory hyperpigmentation (PIH) is an acquired condition in which increased pigmentation occurs as a consequence of cutaneous inflammation from a wide range of aetiologies including inflammatory dermatoses, infections, allergic reactions, mechanical injuries, reactions to medications and therapeutic procedures. 1 3 PIH can be observed in individuals at any age or gender. 3 However, it is commonly seen in darker skinned individuals with Fitzpatrick SPTs III VI. 3 6 Clinically, PIH develops in the same area as the preceding inflammation. 3 Colour of a lesion may range from light brown to slate-grey or black depending on the location of melanin deposition, which can be found in the epidermis and the dermis. 1,3,4,7,8 Wood s lamp examination and or infrared photography are helpful in determining subtle degree of PIH. 8,9 Histologically, excess epidermal melanin and dermal pigmentation have been described. 1,2 Although PIH usually spontaneously remits, it often fades away slowly, sometimes persisting for years. 3 Thus, PIH can cause significant anxiety and lowered selfesteem in affected individuals. Degree of PIH has been observed to be higher in prolonged and or recurrent inflammation, when compared with short-term acute inflammation. 8 It has been proposed that degree of hyperpigmentation is directly relate to the severity of inflammation or degree of basal layer dermo epidermal junction injury, as observedinlichenoiddermotosessuchaslichenplanusanderythema multiforme. 3,4,10 A study of Takiwaki et al. 10 in 16 healthy male Japanese with SPT III observed a linear relationship between erythema and melanin indices measured from the skin areas that received ultraviolet B (UVB) irradiation. Moreover, erythema and pigmentation were suppressed significantly by the application of topical anti-inflammatory agents immediately after UVB irradiation. Aforementioned study implies that that the intensity of the inflammationcorrelatedwiththedegreeofpih,andinflammation had some roles in melanogenesis. There have been several evidences that may help explain how PIH develops. The inflammation of the epidermis induces production and release of various keratinocyte-derived mediators, including prostaglandins, leukotrienes and many cytokines that affect melanocyte proliferation and melanin production. 3,11,12 Previous studies suggested that these reactions may be in response to some stimuli such as ultraviolet radiation and inflammation or inflammatory mediators. Moreover, there are some changes observed in melanocyte, including hyperplasia and hypertrophy The inflammatory response of the epidermis may result in an increase in melanin pigment in the epidermis (epidermal hyperpigmentation). 3,11 Pigmentary incontinence (Incontinentia pigmenti histologica), or a melanin dropping may cause dermal hyperpigmentation, of which, melanosomes (melanin granules) are found

2 8 Eimpunth et al. in the macrophages (melanophages) in the dermis. 3,20 The evolution of this type of PIH begins with cutaneous inflammation that causes injury to the basal cell layer, such as lichenoid dermatoses. 20 Then, the degenerating basal keratinocytes and melanosomes were phagocytized by macrophages, resulting in melanophages accumulation in the upper dermis. 3,4,20 It is known that cutaneous manifestations and response to stimuli among races is different, and Asians and other dark-skinned populations are more prone to develop PIH. 3 6,21 26 This review focuses on the PIH following acne and aesthetic procedures in Asians. Acne-induced and aesthetic procedure-related postinflammatory hyperpigmentation Postinflammatory hyperpigmentation is a common consequence of acne, especially in dark-skinned individuals. 19,27 According to a population-based study by Perkins et al., 28 PIH was found in African American and Hispanic more than Caucasian, Asian and Continental Indian women. PIH is clinically apparent at a certain period of time after the erythema from acne subsides (Fig. 1). 4,29 Most of the time, PIH occurred can remit spontaneously, however, very slowly in some cases. 4 Interestingly, in dark-skinned patients, PIH from acne disturbs some patients, psychologically, more than the active lesions itself. 25,30,31 Thus, for acne treatment, particularly when dealing with dark-skinned patients, the treatment of PIH should be incorporated in their acne treatment regimen. 19,32,33 As the hyperpigmentation is a result of the inflammation, effective and adequate control of the inflammation is crucial to prevent and to minimize theseverityandthecourseofpih. 4 An occurrence of PIH following aesthetic procedures and lightbased treatments is not uncommon, especially in darker skinned patients such as Asians, African American and Hispani (Fig. 2). In essence, darkening of the skin may occur after any aesthetic, and and light procedures causing inflammation to the skin. PIH can last from months to years after the procedure has been performed (Fig. 3). An incidence of PIH following ablative fractional CO 2 resurfacing in Thai patients with SPT IV can be as high Figure 1. A 25-year-old Thai (skin phototype IV) man with postinflammatory hyperpigmented macules over the mandibular area, presented after the erythema from active acne subsided. Figure 2. Postinflammary hyperpigmentation developed 2 weeks after hair removal with a long-pulsed 1064-nm Nd:YAG in an Indian woman with skin phototype V. as 92% (Fig. 4), 34 whereas an incidence of 23% observed in a study in SPTs I III patients using a similar type of ablative fractional CO Table 1 illustrates studies of aesthetic and procedures performed in Asians that were complicated with PIH. Treatment of PIH There are several important aspects worth noting in treating PIH. First, the primary treatment of PIH is to prevent and control the ongoing inflammatory condition that may cause further PIH. Second, the prompt initiation of PIH treatment helps hasten its resolution and prevent further darkening of PIH lesions. Lastly, in many circumstances, PIH can develop as a consequence of either the skin conditions themselves, or from cutaneous irritation caused from the treatment of the active lesions or PIH. 3,4,29,36 Therefore, any treatments considered should be able to aggressively and adequately control the pigmentation and the inflammation of primary lesion, while being gentle enough to the skin. Sun avoidance and non-comedogenic sunscreen should be advised and included in the treatment regimen because sun exposure may prolong the resolution of PIH. 4,33 In addition, patents should be instructed to avoid any physical trauma, such as scratching or rubbing to the skin that may worsen the degree of PIH. Any concurrent medications that may make PIH worse, such as tetracycline, should also be taken into account. Topical treatment is an effective treatment modality and should be considered as the first-line treatment for PIH. 4 Topical hydroquinone (HQ), a gold standard treatment of PIH, can be used safely for up to 6 months and can be introduced either early in the acne treatment programme or later when the acne is improved. 29 Topical retinoids can be applied for both acne and PIH treatment. 19,37,38 The efficacy of tretinoin on the treatment

3 Postinflammatory hyperpigmentation in Asians 9 (a) (b) (c) (d) Figure 3. A 24-year-old Thai Chinese woman (skin phototype IV) with acquired bilateral nevus of Ota-like macules (Hori s nevus). (a) Before treatment, (b) 1 week after treatment with a 1064-nm QS Nd:YAG, (c) postinflammatory hyperpigmentation developed at 2 weeks after treatment. The intensity of the pigmentation is usually darker than the colour of the primary lesions, (d) 3 months after seven treatment sessions. Figure 4. Postinflammatory hyperpigmentation following an ablative fractional CO 2 resurfacing in a Thai man with skin phototype IV. of PIH has been demonstrated. 2,19 Topical tazarotene 0.1% cream has proven effective for treatment of acne, dyspigmentation in photoaging and PIH. 38 A combined topical retinaldehyde 0.1% and glycolic acid (GA) 6% preparation also provided some benefit in acne and PIH treatment. 39 Azelaic acid is another effective agent for both acne and PIH treatment. 40 Topical medications such as kojic acid and licorice extract are also effective treatment of choice for PIH. 2,33 Agents that have been studied and reported to provide beneficial response in the treatment of PIH from acne are listed in Table 2. In general, combination treatment is favoured because it enhances the treatment efficacy while minimizing side-effects that may occur with monotherapy. 4 From topical acne treatment, iatrogenic PIH may occur as a result of irritation, irritant contact dermatitis. Therefore, topical treatment regimen should be tailored carefully to minimize irritation that may occur. This can be achieved by using the lowest concentration and least irritating products possible. Moreover, moisturizers might be incorporated in the regimen, either by means of choosing product with moisturizing vehicles or adding moisturizer as a part of the regimen. 41,42 Single topical agent can be used as monotherapy for PIH. However, combination therapy is preferred because with combination treatment, the clinical outcome will be enhanced. 3,4 The most commonly used combination preparation for PIH is the formula containing HQ, retinoic acid (RA) and corticosteroids. In this formula, the irritation might occur from HQ and RA and may worsen the hyperpigmentation. 4,8 Other topical agents that can be considered for PIH treatment include kojic acid, licorice, arbutin, ascorbic acid, soy, N-acetyl glucosamine and niacinamide. 43 Chemical peelings and treatment are considered as second-line therapy for treating recalcitrant PIH. Importantly, these second-line therapies have a higher risk of worsening the PIH condition compared with that of topical depigmenting agents. The role of chemical peelings and treatment in treatment of PIH may be primarily for pigmented lesions that remain refractory after several months of topical therapy. A retrospective study on acne PIH noted an optimal clearing of PIH by 3 months after using topical lightening agents. 4 This period may be an appropriate timing to start using second-line treatments to further optimize the therapeutic outcome. Superficial chemical peels with either GA or salicylic acid (SA) can be used in dark-skinned acne patients. 33 Grimes 44 performed a study using five treatments of 2-week interval SA peels for melasma, oily rough skin, acne and PIH in SPTs V VI patients, and reported that 100% of PIH

4 10 Eimpunth et al. Table 1 Studies related to postinflammatory hyperpigmentation (PIH) after aesthetic and procedures in Asians Procedure Year Nationality Authors Subject Treatment protocol Postinflammatory hyperpigmentation Chemical peels 2002 Iraqi Al-Waiz and Al-Sharqi Dark-skinned patients with acne scars Transcutaneous focused ultrasound IPL combined with QS ruby Pigmentspecific 2011 Chinese Chan et al Chinese patients with facial skin laxity, SPTs III IV. A total of 68 treatments 2008 Korean Park et al Females with complex dyspigmentation of the face 2012 Chinese Ho et al Chinese patients with freckles or lentigines 2011 Taiwanese Chang and Kou Patients with nevus of Ota Japanese Negishi et al Patients with a total of 355 solar lentigines, SPTs III V 2009 Korea Lee et al Females and two males with ABNOMs Indian Aurangabadkar Patients with nevus of Ota, SPTs IV and V Medium-depth peel using Jessner s solution followed by 35% trichloroacetic acid Total 1 3 treatments 1 3 full-face treatments at 4-week intervals All patients were initially treated with IPL, followed by QS ruby, either on the same session or within 1 week after IPL treatment. Patients received an average of 2.88 and 1.52 treatments with IPL and QS ruby respectively Four groups: nm long-pulsed (LP) dye nm LP Alexandrite nm QS Nd:YAG nm LP KTP 1 4 treatments (mean 1.8) at 4 6 weeks interval 47 were treated with QS ruby and 47 were irradiated with 1046-nm QS Nd:YAG Four groups: 694-nm QS ruby, aggressive 694-nm QS ruby, mild 532-nm QS Nd:YAG, aggressive 532-nm QS Nd:YAG, mild Single treatment All subjects were treated with a 1064-nm QS Nd:YAG up to 10 sessions nm-qs Nd:YAG Multiple treatments over 1-year period 73.4% of the subjects developed PIH and resolved within 3 months Two of 49 (4%) cases had PIH spot, approximately 2 mm in diameter, on the forehead and completely resolved at 9 months after treatment Three of 25 (12%) patients were complicated with mildto-moderate PIH in the areas treated with QS ruby Occurrence of PIH: Group 1. None Group 2. 20% Group 3. 10% Group 4. None Transient PIH was found in 6.4% and 10.6% in QS ruby and QS Nd:YAG groups respectively. PIH incidence was different between groups Group 1: 33.33% Group 2: 7.47% Group 3: 23.18% Group 4: 8.47% 40% of the patients experienced PIH, which persisted for 1 month. Transient PIH in five patients (10%) which was cleared with treatment within 2 months

5 Postinflammatory hyperpigmentation in Asians 11 Table 1(Continued) Procedure Year Nationality Authors Subject Treatment protocol Postinflammatory hyperpigmentation 2007 Thai Manuskiatti et al Females with ABNOMs 2006 Japanese Kono et al Asians with lentigines with SPTs III IV 2003 Thai Manuskiatti et al Thai women with acquired bilateral nevus of Ota-like macules (ABNOMs) 2003 Thai Angsuwarangsee and Six females treated with Polnikorn 85 refractory melasma. One side of the lesion in all patients was randomly treated with 1064-nm QS Nd:YAG, whereas the other side was treated with the same and parameter together with cold air cooling device. One of the lentigines present was treated with LPDL with compression method and the other one was treated with QSRL. Of all patients, one side of their lesion was randomly treated with QS ruby only, whereas the other side was treated with a CO 2 resurfacing, followed by QS ruby. All subjects were treated with ultrapulse CO 2 and QS alexandrite (QSAL) on one side and QSAL alone on the other side 2000 Thai Polnikorn et al Asians with ABNOMs All subjects was treated with 1064-nm QS Nd:YAG at 3- to 6-month interval. 595-nm PDL 2012 Thai Treewittayapoom et al Patients with bilateral fingernail psoriasis Laser hair removal 1320-nm Nd:YAG 40 Nails were treated with 6-ms pulsed duration and 9J cm 2 and 39 nails were irradiated with 0.45 ms pulsed duration and 6 J cm Chinese Yeung et al Patients, SPTs III IV All patients got one 1064-nm LP Nd:YAG treatment coupled with a pneumatic skin flattening (PSF) on the right axilla and dynamic cooling device (DCD) on the other side Chinese Chan et al Patients with acne scars or wrinkles Five out of 21 (24%) and 13 of 21 (62%) of the subjects developed PIH on the uncooled and cooled sides respectively. PIH was noted in four of 18 (22.2%) subjects treated with QSRL, but not with LPDL. At 1-month follow-up, 54% (7 13 patients) and 46% (6 13) of the patients had pigmentary changes (hypoand hyperpigmentation) on the side treated with QS ruby alone and the side treated with CO2 + QS ruby s respectively. Three of six cases (50%) got PIH on both sides occurred at 2 4 weeks postoperatively and began to fade away around the 3rd month PIH was noted in 73% of cases and faded in 2 6 months after using 2 6% hydroquinone (HQ) cream. PIH occurred in 30% and 28.2% of patients on the 6 ms and 0.45 ms groups respectively. PIH developed in 9.1% and 18.2% of the patients on the DCD and PSF sides respectively. Monthly 5 6 treatment sessions Three cases (11.1%) and all cases resolved after 4% HQ treatment

6 12 Eimpunth et al. Table 1(Continued) Procedure Year Nationality Authors Subject Treatment protocol Postinflammatory hyperpigmentation 1450-nm diode 2940-nm, variable square pulse (VSP) Er:YAG Fractional radiofrequency (RF) combined with fractional 915-nm Fractional 1540-nm Erbium glass 2009 Chinese Yeung et al Patients (SPTs IV V) with inflammatory facial acnes 2006 Singaporean Chua et al Patients (SPTs IV V) with facial atrophic acne scars 2006 Singaporean Tay et al. 11 Subjects (SPTs IV VI) with stretch marks on the body 2010 Thai Manuskiatti et al Thai women with peri-orbital wrinkles Thai Waniphakdeedecha 24 Patients (SPTs III V) et al. 93 with punched-out atrophic and rolling acne scars Thai Waniphakdeedecha 20 Women with et al. 94 epidermal-type melasma Chinese Yeung et al Patients (SPTs III IV) with acne scars 2007 Chinese Chan et al Chinese patients with acne scars, photoaging and pigmentation A total of four full-face treatments were given at 3- to 4-week intervals. A total of 4 6 treatment sessions were given at 4 weeks apart. All patients received three treatments at 6-week intervals. All patients got two treatments of a low-fluence, VSP Er:YAG 1 month apart. Twelve patients were randomly treated with a pulse duration of 0.3 ms and the rest were treated with a pulse duration of 250 ms. All subjects were treated monthly with a VSP Er:YAG for two sessions. All subjected were divided into two groups and received two different pulse widths including 0.3 and 1.5 ms. Two monthly treatments of VSP Er:YAG were performed in all subjects. Up to five treatments with combined fractional, followed by fractional RF were performed. Total 119 treatments, 68 high energy low density, 51 low energy high density Four episodes (3.8%) of PIH were observed out of all treatment sessions. PIH was noted in 39% of 57 patients. PIH occurred in 64% (7 11) of the cases. PIH occurred in 13% (6 of 46) of the total treatment sessions. Transient PIH was observed in 18% of the subjects of both treatment groups. Mild PIH occurred in 11.8% of the subjects and clear spontaneously in 2 weeks. PIH developed mainly over the bony areas in 6.5% of treatment sessions and in 8.3% of 24 treated patients. Mild-to-moderate generalized PIH occurred in low energy, high density more than high energy, low density (12.4% vs. 7.1%), not statistically significant difference.

7 Postinflammatory hyperpigmentation in Asians 13 Table 1(Continued) Procedure Year Nationality Authors Subject Treatment protocol Postinflammatory hyperpigmentation Fractional 1550-nm erbium-doped fibre Fractional ablative carbon dioxide (CO 2 ) Combined conventional CO 2 and fractional CO2 Combined fractional RF and fractional 915 nm 2010 Chinese Chan et al Asian patients with facial atrophic acne scars, SPTs III V 2009 Korea Lee et al Patients (SPTs III IV) with facial wrinkles 2010 Thai Manuskiatti et al Thai patients with atrophic acne scars, SPT IV 2010 Chinese Chan et al Chinese patients with photoaging and acne scars, SPTs III and IV 2012 Chinese Huang Chinese patients with acne scars, SPT IV 2012 Chinese Yeung et al Chinese patients with acne scars, SPTs III IV Total 92 treatments Two treatment settings 1. full-nafr : 8 passes 2. mini-nafr : 4 passes of comparable pulse energy and treatment level, but double the number of treatment sessions All patients received 2 3 treatments, 2-weeks apart. Three treatment sessions on an average of 7-week interval Energy levels mj with coverage between 30% and 45% One full-face treatment A minimum of two treatments (range 2 7) at 2- to 6-month intervals The PIH risk was significantly different. For full-nafr, the PIH risk was 18.2% compared with 6% for mini-nafr. No significant difference in clinical efficacy between two treatments One of 27 (4%) cases had transient PIH. Mild PIH developed in 92% of the subjects or 51% of treatment sessions Completely resolved in an average of 5 weeks The PIH rate was 55.5% and 11.1% at 1 and 6 months after treatment 22 Patients (50%) had temporary PIH ( 1 month) and four patients (9%) had PIH 3 months Up to five treatments PIH developed in four patients in 6 of the total 92 treatment sessions (6.5%) and most lesions faded within 2 months IPL, intense pulsed light; SPTs, skin phototypes; QS, Q-switched; ABNOMs, acquired bilateral nevus of Ota-like macules; PDL, pulsed dye ; ms, millisecond; NAFR, non-ablative fractional resurfacing; LP, long pulsed; KTP, potassium-titanyl-phosphate; LPDL, 595 nm long-pulsed dye.

8 14 Eimpunth et al. Table 2 Studies related to the treatment of postinflammatory hyperpigmentation (PIH) from acne in Asians Year Authors Subjects Intervention Outcome 2006 Grimes and 74 Patients with acne and PIH, Callender 38 darker racial ethnic group 2010 Kim and 40 Korean patients with PIH and Cho 46 mild-to-moderate acne, SPTs IV V 2011 Ho et al Chinese patients with PIH from acne, SPTs III V 2011 Kircik Patients with mild-to-moderate acne and moderate-to-severe PIH, SPTs V VI 2012 Callender 33 Patients with mild-to-moderate et al. 99 facial acne and PIH, SPTs IV VI 2012 Godse and 20 Indian patients with PIH from Sakhia 36 acne, SPTs IV V Tazarotene 0.1% cream with vehicle controlled, once daily Two groups (20 each) 5 weekly treatments of Group 1: Full-face low-fluence 1064 nm QS Nd:YAG with comedone extraction and intralesional injections for severe inflammatory papules and topical 4% benzoyl peroxide gel twice daily Group 2: Only comedone extraction and intralesional injections for severe inflammatory papules and topical 4% benzoyl peroxide gel twice daily Retrospective study: three groups 1. Topical agents nm long-pulsed dye and or 1064-nm QS Nd:YAG at 4- to 6-week intervals 3. Combination topical and treatments Azelaic acid 15% gel, twice daily for 16 weeks Two groups 1. A topical gel containing 1.2% clindamycin phosphate and 0.025% tretinoin 2. Placebo Duration: 12 weeks Triple combination of 2% hydroquinone, 0.05% tretinoin and 0.01% fluocinolone acetonide cream with three glycolic acid peels at 2-week interval Tazarotene 0.1% cream was effective and well tolerated for PIH treatment Low-fluence 1064 nm QS Nd:YAG treatment was effective for PIH All three groups: Significant improvement of PIH Between groups: No significant difference was found Both acne and PIH were improved Acne: A combined 1.2% clindamycin and 0.025% tretinoin gel provided better result compared with the placebo PIH: Slight improvement in PIH was found from the combined clindamycin tretinoin gel, and it was superior to the placebo After treatments, 12 patients had more than 50% improvement in PIH and three patients showed more than 75% improvement. SPTs, skin phototypes; QS, Q-switched.

9 Postinflammatory hyperpigmentation in Asians 15 patients had moderate to significant improvement. Garg et al. 45 compared 35% GA vs. 20% salicylic 10% mandelic acid combination peels (SMPs) for active acne, acne scars and hyperpigmentation in 44 Indian patients and found that both agents were effective, but SMPs gave superior results for both active acne lesions and hyperpigmentation. Lasers 4,46 51 and pulsed light source 52 have been used to treat PIH with variable success. Vascular, such as the 595-nm long-pulsed dye (LPDL), can be used in the treatment regimen of acne-induced PIH. It works by treating the vascular component of the inflammation; thus, shortens and lessens the inflammatory process, and, as a result, reduces the PIH risk. Another mechanism of action of LPDL may due, partly, to its ability in treating pigmentary lesion, when used with compression. 4 Pigment-specific, such as 1064-nm Q-switched (QS) Nd:- yttrium aluminum garnet (YAG) can be used in PIH treatment when using at a low-fluence setting. 47 Kim and Cho 46 demonstrated effective treatment by low-fluence QS Nd:YAG of acne PIH in SPTs IV VI patients. As anticipated, PIH can also be developed as a side-effect from this treatment technique for PIH. 4 Laser toning using low fluence, large spot size, multiple passed QS 1064-nm Nd:YAG for skin rejuvenation, melasma and treatment of PIH has recently gained much popularity, especially in Asian countries however, there are still very few evidence-based data supporting this approach in the treatment of PIH and melasma. 46,47,53,54 In toning, multiple passes of low-fluence (e.g J cm 2 ) are delivered through a large spot size (e.g. 6 8 mm) to optimize energy delivery and to achieve mild erythema as the clinical endpoint. Some physicians have proposed the daily usage of toning for skin rejuvenation, while others offer treatments at weekly, 2-weekly, or monthly intervals with a wide variation in the total number of treatment. 55 Confetti-like or spotty hypopigmented macules or punctate leucoderma 55,56 and rebound hyperpigmentation are common sideeffects associated with low-fluence QS 1064-nm Nd:YAG for skin rejuvenation and melasma. 57 Recently, Chan et al. 55 assessed a case series of 14 Chinese patients with toning-associated facial depigmentation with cross-polarized and ultraviolet (UV) photographic images. Of all 14 patients, nine received toning for non-ablative skin rejuvenation and the other five for melasma. Treatment protocols received by these patients were highly variable. The total number of treatments received ranged from 6 to 50 (mean 22). In all cases, UV photographic images demonstrated facial mottled depigmentation. Laser toning failed to significantly improve melasma in all five patients. Non-ablative fractional resurfacing (NAFR) has shown inconsistent results for treatment of PIH A previous study demonstrated transepidermal elimination of dermal component through incorporation into microscopic epidermal necrotic debris. The expulsion of dermal pigment in conjunction with the affected microthermal zones (MTZs) is the most likely mechanism of action when treating dermal pigmentary disorders including melasma, drug-induced hyperpigmentation and PIH. 58 However, PIH itself is the most common adverse effect following NAFR and ablative fractional resurfacing (AFR) 34,62 in Asian individuals. Graber et al. 60 retrospectively studied 961 treatments with the 1550-nm erbium-doped fibre and found that PIH occurred more frequently in darker skin types (incidence of 2.6%, 11.6% and 33% for skin type III, IV and V respectively), appeared later posttreatment and lasted longer than other complications. Previous studies investigating the use of NAFR 61,63 and AFR 35 indicated that treatment density, rather than energy, was a stronger determining factor in the development of PIH in predisposed patients. Therefore, to reduce the risk of PIH associated with NAFR and AFR when treating Asian patients, the total treatment density (MTZ cm 2 )shouldbereduced.however,ontheother hand, the total number of treatment sessions should be increased to maintain the clinical efficacy. Prevention of postinflammatory hyperpigmentation Various attempts have been made to reduce the occurrence of PIH after treatment in Asian skin. These include sun avoidance, the use of preoperative and postoperative treatment regimens, treatment using conservative energy setting and epidermal protection. Sun exposure before and after treatment has been shown to interfere with skin pigmentation by increasing epidermal melanin pigmentation and epidermal thickness leading to a change in the optical property of the skin In our practice, several recommendations to minimize the effects of UV light have been suggested. From a practical standpoint, it is not easy to avoid sun exposure when living in tropical countries. Most treatments are elective surgeries. Thus, surgery may be postponed during summer months. Topical sunscreens protecting against both UVA and UVB usually zinc oxide based should be applied regularly at least 6 weeks prior to the treatment to obtain the optimal outcome. Patients should not visit tanning booths or go sunbathing, although the influence of acquired pigmentation compared with constitutional pigmentation for the development of adverse effects remains unidentified. The advantage of preoperative treatment regimens with various topical bleaching agents remains controversial. A randomized, controlled study in 100 consecutive CO 2 resurfacing patients (SPTs I III) has not showed the difference in the incidence of PIH after treatment between subjects who received pretreatment with either topical GA cream or combination tretinoin HQ cream, and those who received no pretreatment regimens. 67 In practice, we often observe that PIH occurred even with careful preoperative treatment with topical depigmenting agents, and this complication resolved spontaneously without using any topical preparations other than a broad-spectrum sunscreen and sun avoidance.

10 16 Eimpunth et al. The application of conservative energy setting is another technique used to reduce the risk of PIH. A recent study on the treatment of lentigines in Japanese patients using 532-nm, QS Nd:YAG and QS ruby s suggested that the use of lower energy setting (using slight immediate whitening as an endpoint) did not decrease the treatment efficacy and had a significant lower incidence of PIH, when compared with that of high-energy setting (using very obvious immediate whitening of the pigmented lesion as a treatment endpoint). 68 Tranexamic acid (TA), a plasmin inhibitor, has been found to prevent UV-induced hyperpigmentation in guinea pigs. 69 The mechanism of pigmentary inhibition of TA is unknown. A previous study suggested that TA inhibits melanin synthesis in melanocytes by interfering with the interaction between melanocyte and keratinocyte through inhibition of the plasminogen plasmin system. 69 Localized intradermal microinjection of TA has demonstrated a promising result in melasma treatment. 70 However, oral TA given postoperatively failed to prevent PIH after QS ruby treatment for senile lentigines in Japanese patients. 71 Short-term use of prophylactic systemic prednisolone has been anecdotally used to reduce the risk of posttherapy inflammatory reactions and related pigmentary alterations in Asian individuals. 72 Corticosteroids are believed to suppress general activity of cell, leading to the inhibitory effect on melanin synthesis. 14 However, use of corticosteroids postoperatively is controversial as it may interfere with the normal wound-healing process and may increase the risk of infection. Recently, Ortiz et al. reported two cases of patients having bacterial infection after the application of a high-potency topical corticosteroid following ablative resurfacing. It is uncertain whether a short application of potent topical corticosteroids can predispose the patients to infection. However, a previous animal study has not found an increase in infection rate in steroidtreated burn wounds. 73 Lowering the temperature of the skin s surfaces is a method for selectively controlling the depth at which heat is produced in the skin by s or light sources. The effect of epidermal cooling has been shown to enhance clinical efficacy and minimize epidermal damage caused by the treatment process. 74 Although epidermal cooling is supposed to reduce patient s discomfort during treatment and to minimize the risk of PIH, it may also induce PIH. 75,76 Conclusion Management of PIH remains a challenge, especially in darkskinned individuals. The primary treatment of PIH is prevention and treatment of the underlying inflammatory condition. Although many treatment options available for PIH, it yet takes months for PIH to resolve, even with an adequate therapy. Thorough patient counselling regarding the natural course of PIH and itsmanagementplanisahelpfultooltogetthepatientsthrough the psychological stress of this condition. References 1 Callender VD, St Surin-Lord S, Davis EC et al. Postinflammatory hyperpigmentation: etiologic and therapeutic considerations. Am J Clin Dermatol 2011; 12: Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol 2010; 3: Lacz NL, Vafaie J, Kihiczak NI et al. Postinflammatory hyperpigmentation: a common but troubling condition. Int J Dermatol 2004; 43: Ho SG, Yeung CK, Chan NP et al. 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