The Asian Dermatologic Patient: Review of Common Pigmentary Disorders and Cutaneous Diseases

Stephanie G.Y. Ho; Henry H.L. Chan

Disclosures

Am J Clin Dermatol. 2009;10(3):153-168. 

In This Article

2. Disorders of Pigmentation

2.1 Post-Inflammatory Hyperpigmentation

Post-inflammatory hyperpigmentation (PIH) is a common pigmentary disorder in melanin-rich Asian skin.[12] PIH can be considered the default pathophysiologic response to cutaneous injury in such individuals. Several factors contribute to the development of PIH, including increased melanocytic activities, dermal melanophages, and hemosiderin deposition secondary to hemorrhage. The severity of PIH is related to the degree of inflammation and extent of disruption of the epidermo-dermal junction. It may be caused by endogenous inflammatory skin disorders or iatrogenic sources such as lasers.[13] The high epidermal melanin content in Asian skin may act as a competing chromophobe for vascular and pigment lasers, interfering with the absorption of laser energy that is intended for another target. With increasing use of lasers and light sources in Asians, prevention and management of PIH is becoming increasingly important.[14] This will be discussed in more detail in subsequent sections.

2.2 Melasma

Melasma is an acquired symmetric hypermelanosis involving sun-exposed areas commonly seen in Asian middle-aged women. Genetics, UV radiation, pregnancy, hormonal therapies, and other phototoxic drugs are all thought to be contributing etiologic factors and melasma remains a difficult condition to treat. Melasma was formerly classified histopathologically as epidermal, dermal, or mixed type depending on the location of the pigment.[15] However, Kang et al.,[16] in a histopathologic study of 56 Korean patients with melasma, suggested that there is no true dermal type and the dermal melanophages seen in 'dermal-type melasma' may be due to undiagnosed acquired bilateral nevus of Ota-like macules or Hori's macules.

In a study comparing the histopathologic features of melasma with those of normal skin using several different immunohistochemical stains, Kang et al.[16] reported that melasma skin had more melanin in the whole epidermis whereas melanin is confined to the basal layer in normal skin. Increased numbers of melanocytes and widely dispersed melanosomes in keratinocytes are also found in melasma lesions. These investigators proposed that increased activity of melanogenic enzymes results in hyperactive melanocytes with increased synthesis and transfer of melanosomes, and decreased degradation in keratinocytes. Sublethal laser damage to these labile melanocytes can increase the production of melanin and lead to PIH.[16] This may explain why previous studies using a 510-nm pigmented lesion dye laser[17] and a Q-switched (QS) ruby laser[18] for the management of melasma led to little improvement and worsening of pigmentation in some cases. Recent studies have also indicated that intense pulsed light (IPL) can lead to manifestation of previously subclinical melasma; for this reason, Wood's light examination or UV photography prior to IPL treatment of Asian skin is recommended.[19,20]

Use of bleaching agents and sunscreens for at least 6 weeks, and preferably for 3 months, prior to any laser or light therapy can help suppress the function of these hyperactive melanocytes and reduce the risk of PIH.[14] Even with such precautions, a recent study in Taipei[20] that compared topical bleaching treatment only with bleaching plus IPL treatment for melasma reported two cases of PIH in the IPL-treated group despite prolonged use of bleaching agents and sunscreens prior to treatment.

Combinations of hydroquinone with topical corticosteroids and tretinoin have been reported to be effective as first-line treatment of melasma.[21,22] The limitations of topical treatment include the longer time required for effectiveness to become apparent and patient compliance. Glycolic acid, salicylic acid, and trichloroacetic acid peels are also useful adjuncts to topical treatments in the management of melasma in Asians.[23,24,25]

Wang et al.[20] in Taipei showed that patients with melasma in the IPL-treated group achieved a significant improvement of 39.8% compared with 11.6% in the control group after four sessions of IPL and topical treatment. However, partial repigmentation was noted 24 weeks later, suggesting the need for repeated treatments for maintenance. These investigators suggested use of the lowest fluence to achieve minimal erythema, a recommendation supported by the findings of Negishi et al.[19] This avoids excessive thermal injury to labile melanocytes and reduces the risk of PIH.

Ablative lasers such as carbon dioxide lasers and QS alexandrite lasers have been used with some success in the treatment of melasma.[26,27,28] These lasers are thought to prevent the clonal expansion of hyperactive melanocytes located in the epidermal basal layer. In addition, ablative lasers may increase the topical absorption of bleaching agents in patients with impaired epidermal barrier function. However, the significant downtime and adverse effects associated with the use of ablative lasers has made them unpopular.

Fractional skin resurfacing is a recent development in the management of melasma (figure 1). This involves the use of a 1540-nm laser that creates microscopic zones of thermal injury that are surrounded by normal skin. As the areas of thermal injury are very small, lateral migration of keratinocytes to them occurs rapidly, leading to re-epithelialization of the epidermis within 24 hours.[14] Rokhsar and Fitzpatrick[29] conducted a small study that evaluated use of fractional resurfacing (Fraxel®, Reliant Technologies, Mountain View, CA, USA) in the treatment of melasma. In their ten subjects, using 6-12 mJ at 2000-3500 microthermal treatment zone (MTZ)/cm2 as treatment parameters, 60% reported 75-100% clearing of melasma, 30% reported <25% clearing of melasma, and one case developed PIH. No downtime was required for wound healing.

Figure 1.

Treatment of melasma with fractional skin resurfacing: (a) pre-treatment; (b) post-treatment.

2.3 Freckles and Lentigines

Freckles and lentigines are common benign pigmented lesions seen in Asians. As the cultural trend in Asians moves towards fair porcelain skin, these pigmented lesions can often present in dermatology outpatients as a cosmetic concern.

Freckles or ephelides occur in adolescence and are relatively uniform in distribution, size, and color. Histopathologically, epidermal hypermelanosis without an increase in melanocyte number is seen. Lentigines increase in number and prevalence with age. They tend to vary in size and color and are non-uniformly distributed. Histologically, the number of melanocytes and epidermal hypermelanosis are increased and the epidermal rete ridges are elongated.[30]

Anderson et al.[31] were the first to demonstrate the effectiveness of QS neodymium-doped yttrium aluminum garnet (Nd:YAG) laser in the treatment of cutaneous pigmentation. However, studies using QS Nd:YAG, QS ruby, and QS alexandrite lasers for pigmented lesions in Asians have reported a PIH risk of around 25%.[30,32,33] Chan et al.[33] compared the use of different types of 532-nm Nd:YAG lasers in the treatment of facial lentigines in Chinese patients and found similar effectiveness for the QS Nd:YAG and long-pulsed Nd:YAG. However, there was a higher risk of post-operative hyperpigmentation with the QS device. It has been suggested that unlike the long-pulsed laser that causes tissue destruction purely by photothermolysis, the QS Nd:YAG laser, with its high-energy nanosecond radiation, exhibits both photothermal and photomechanical effects. The undesirable photomechanical effect induces damage to surrounding oxyhemoglobin as well as target melanin, resulting in inflammation of superficial vessels, altered activity of melanocytes, and subsequent PIH.[34] Results from other studies also support the theory that long-pulsed devices are more suitable for Asian skin in reducing the risk of PIH.[30,35]

IPL sources emit a broad band of visible light from a non-coherent filtered flashlamp and produce photothermal effects only.[36] There have been several studies confirming the effectiveness of IPL in the management of epidermal pigmentation in Asians. Negishi et al.[35,37] conducted two studies that evaluated photorejuvenation using IPL. Results from the first study involving 97 Asian patients (cut-off filter 550 nm, 28-32 J/cm2, double-pulse mode of 2.5-4.0/4.0-5.0 msec, delay time 20.0/40.0 msec) showed that >90% of patients reported a reduction in pigmentation after three to six treatments at intervals of 2-3 weeks.[35] The second study used IPL with an integrated contact cooling system (cut-off filter 560 nm, 23-27 J/cm2, double-pulse mode of 2.8-3.2/6.0 msec, delay time 20.0/40.0 msec) and, in this study, 80% of the 73 patients evaluated had a significant reduction in pigmentation after three to five treatments at intervals of 3-4 weeks.[37] Kawada et al.[38] evaluated 60 patients with solar lentigines and freckles and reported more than 50% improvement in 68% of these patients following three to five IPL treatments at intervals of 2-3 weeks (cut-off filter 560 nm, 20-24 J/cm2, 2.6-5.0 msec pulse duration in double or triple pulses, delay time 20 msec). Freckles responded better than lentigines. Interestingly, post-operative PIH was not seen in any of these studies, highlighting the advantage of IPL as a treatment choice for photorejuvenation in Asian patients.

A treatment algorithm relating to use of lasers and IPL sources for the treatment of acquired pigmentary lesions in Asians has been put forward by Chan[36] to help physicians weigh up issues such as cost effectiveness, clinical outcome, and adverse events such as PIH. This author suggests IPL for patients who demand a low risk of PIH and who are amenable to having several treatment sessions. A median approach using long-pulsed Nd:YAG may be considered if a faster outcome is desired. An aggressive approach using QS lasers requires only one to two sessions, which make this approach the most time- and cost-effective approach; however, it also carries the highest risk of PIH and necessitates a downtime period of 1 week.

Other means of reducing PIH in Asians include diascopy during laser therapy to compress and empty dermal vessels in order to reduce the risk of dermal vascular damage and hemosiderin deposition. Kono et al.[39] recently compared the efficacy and complications seen with use of the QS ruby laser and the 595-nm-long pulsed dye laser (PDL) delivered with a compression method in the treatment of lentigines. The efficacy was similar in both groups but there was a much lower risk of PIH in the group treated with the compression technique. Using a laser or light source with a shorter wavelength (350-500 nm) confines the thermal injury to the epidermal layer and is another means of reducing the risk of PIH.[4]

2.4 Nevus of Ota

Nevus of Ota is a dermal melanocytic hamartoma common in Asians and affects about 0.6% of the population.[40] Clinically, nevus of Ota presents as a bluish hyperpigmentation along the distribution of the trigeminal nerve. QS ruby, QS alexandrite, and QS 1064-nm Nd:YAG lasers have all been used to achieve good therapeutic results.[41] Watanabe and Takahashi[42] evaluated 114 nevus of Ota patients treated with a QS ruby laser and reported a good-to-excellent degree of lightening after three or more treatment sessions. Kono et al.[43] confirmed these findings when they reviewed 101 nevus of Ota patients 12 months after they had been treated with a QS ruby laser and found that 56% reported over 75% clearing and 36% achieved complete clearing. Hypopigmentation was seen in 17% of patients and hyperpigmentation in 6%. Studies comparing the use of QS alexandrite with QS 1064-nm Nd:YAG lasers found the former to be better tolerated but the latter more effective after three or more sessions.[44,45] The risks of hypo- and hyperpigmentation were similar in both treatment groups, with 15% hypopigmentation and 3% hyperpigmentation reported at all treated sites. The risk of recurrence is estimated to be between 0.6% and 1.2%,[43] which has important implications when treating pediatric patients.

2.5 Acquired Bilateral Nevus of Ota-Like Macules or Hori's Macules

Acquired bilateral nevus of Ota-like macules or Hori's macules is a condition that affects 0.8% of the Asian population. Hori et al.[46] described bluish-brown hyperpigmentation typically affecting the bilateral malar regions, forehead, and temples of middle-aged women with no mucosal involvement. Histopathologic findings typically show a circumscribed melanocytosis in the middle and upper dermis.[47] The disorder often coexists with other pigmentary disorders such as melasma and lentigines. QS ruby, QS alexandrite, and QS 1064-nm Nd:YAG lasers have been shown to be effective in the treatment of Hori's macules (figure 2).[48,49,50] However, shorter treatment intervals and more treatment sessions appear to be necessary for a good result. Transient post-operative hyperpigmentation is a common adverse event, occurring in the majority of treated subjects.[49,50] Permanent hypopigmentation has been reported after treatment with a QS ruby laser.[48] A recent study has proposed use of a QS 532-nm Nd:YAG laser followed by a QS 1064-nm Nd:YAG laser to obtain a greater degree of improvement.[51]

Figure 2.

Treatment of Hori's macules using a Q-switched ruby laser: (a) pre-treatment; (b) post-treatment.

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