Freckles and lentigines

Freckles and lentigines are benign pigmented lesions commonly seen in ethnic skin. Freckles occur in adolescence and are relatively uniform in distribution, size and color. Histologically, they are characterized by epidermal hypermelanosis without an increase in melanocyte numbers. Lentigines tend to appear later and vary in size, color and distribution. Histologically, both epidermal hypermelanosis and increase in melanocyte numbers are seen. Epidermal rete ridges are also elongated and clubbed.

As melanin has a broad absorption spectrum ranging from 250 to 1200 nm, various lasers have been used to target cutaneous pigmentation, usually with excellent results. Anderson et al were the first to demonstrate the effectiveness of Q-switched (QS) lasers in the treatment of cutaneous pigmentation. Frequency-doubled QS neodymium : yttrium-aluminum-garnet (Nd : YAG), QS ruby, and QS alexandrite lasers with respective wavelengths of 532 nm, 694 nm, and 755 nm, have all been used with good results in lighter-skinned patients but PIH risk of 10–25% has been reported when used on ethnic skin. Chan et al compared 532 nm frequency-doubled Nd : YAG lasers with different pulse durations in the treatment of facial lentigines in Chinese patients, and found similar efficacy between QS 532 nm Nd : YAG and long pulsed (LP) 532 nm Nd : YAG, but a higher risk of postoperative hyperpigmentation with the QS device. A recent study by our group comparing QS and LP alexandrite for the treatment of freckles and lentigines in 20 Chinese patients showed similar results (Fig. 10.1). There was significant improvement in pigmentation in both groups, with no difference between the groups. However, the risk of PIH was 22% in the QS group, compared with 6% in the LP group. Patients also complained of more severe pain, erythema, and edema with the QS device. These findings were further validated in a retrospective study due to be published, comparing treatment of lentigines in 40 Chinese patients with four different devices; 595 nm long pulsed dye laser (LPDL), 755 nm alexandrite laser, 532 nm QS Nd : YAG, and 532 nm LP potassium-titanyl-phosphate (KTP) laser (Fig. 10.2). The results showed that a long pulse laser and small spot size appear to reduce the risk of PIH in darker skin types (see Case study 1 at end of chapter).

Figure 10.1 Representative clinical responses to the two laser treatments: (A) 3 months post-treatment with QS alexandrite laser; treatment parameters: 3 mm, 5 J/cm², 2 Hz. (B) 3 months post-treatment with LP alexandrite laser; treatment parameters: 4 mm, 13 J/cm², 2 Hz.

Figure 10.2 Management of freckles and lentigines with different pigment-specific lasers: (A) Marked improvement after two treatments with 595 nm LPDL; treatment parameters: 7 J/cm², 10 mm, 6 ms, cooling 3. (B) PIH post single LP alexandrite laser treatment; treatment parameters: 25 J/cm², 1.5 Hz, 3 × 10 mm, DCD 0/20/0, 3 ms. (C) After three treatments with LP 532 nm Nd : YAG; treatment parameters: 2 mm, 13 J/cm², 2 ms, 1 Hz. (D) After three treatments with LP 532nm Nd : YAG; treatment parameters: 2 mm, 13 J/cm², 2 ms, 1 Hz.

LP lasers, with their longer millisecond pulse width, result in more absorption by target melanin and less absorption by competing chromophores such as oxyhemoglobin, and surrounding pigment-laden skin. This is particularly important in reducing the risk of PIH in ethnic skin. The postulated reason is that LP lasers cause melanin destruction by photothermolysis only. In contrast, QS lasers emit high-energy, nanosecond radiation, causing both photothermal and photomechanical effects. Not only is the target pigmented lesion destroyed by the short burst of intense radiation, but surrounding melanin and oxyhemoglobin are also damaged, resulting in altered activity of melanocytes, hemosiderin deposition from damaged vessels, and subsequent PIH.

Spot sizes are also an important consideration when treating darker skin types. From our retrospective study comparing four different laser devices above, we noted that when using LP alexandrite in the treatment of epidermal pigmentation in Asian skin, despite its long pulse width, significant improvement in lesional pigmentation was not found, and was associated with the highest risk of PIH (20%). We postulated that the large spot size (10 mm) in the LP alexandrite laser may have led to inadvertent treatment of surrounding unaffected skin, when the lesion treated is smaller than the spot size available, and this is especially pertinent in ethnic skin where contrast between the lesional and non-lesional skin is low.

There is increasing evidence to support the use of diascopy during laser treatment to reduce the risk of PIH. This is especially true when using pigment lasers that target both oxyhemoglobin and melanin such as the LPDL. Compression of the skin surface by the flat glass window on the handpiece leads to emptying of blood vessels, reducing the risk of vascular damage, and subsequent purpura, hemosiderin deposition, and PIH. The effectiveness of such simple diascopy is supported by results from studies carried out by Kono et al, who conducted different studies using 595 nm LPDL, repeatedly demonstrating its effectiveness and safety when used with compression for the treatment of lentigines in ethnic skin, when compared with IPL and QS ruby laser. Our retrospective study also showed that 595 nm LPDL and 532 nm LP KTP, both of which utilize a compression window, have better results and less complications compared with 532 QS Nd : YAG and 755 nm LP alexandrite laser.

Intense pulsed light (IPL) sources emit a broadband of visible light (400–1200 nm) from a non-coherent filtered flashlamp and target melanin through photothermal effects. Negishi et al carried out two studies looking at photorejuvenation using IPL. Results from the first study involving 97 Asian patients showed that more than 90% reported a reduction in pigmentation after three to six treatments at intervals of 2–3 weeks (cutoff filter 550 nm, 28–32 J/cm², double pulse mode of 2.5–4.0/4.0–5.0 ms, delay time 20/40 ms). The second study used IPL with an integrated cooling system and found 80% of the 73 patients had a significant reduction in pigmentation after three to five treatments at intervals of 3–4 weeks (cutoff filter 560 nm, 23–27 J/cm², double pulse mode of 2.8–3.2/6.0 ms, delay time 20/40 ms). Kawada et al also treated lentigines and freckles in 60 patients with IPL and reported more than 50% improvement in 68% of these patients after three to five treatments at intervals of 2–3 weeks. No PIH was reported in any of these studies. A further split face study comparing QS alexandrite and IPL for freckles and lentigines in Asians found significant improvement with the QS device. However, the risk of PIH was also higher with the QS device, especially in patients with lentigines. No PIH was seen in the IPL group. These studies serve to highlight IPL, through photothermal effects, is effective and safe in the treatment of epidermal pigmentation in ethnic skin. However, multiple treatments are required. Furthermore, with a large spot size, if the contrast between the lesional and non-lesional skin is low, the therapeutic window is much narrower. Either the operator uses suboptimal energy leading to minimal effectiveness, or above threshold energy that may lead to greater risk of injury to surrounding normal skin.

A treatment algorithm for epidermal pigmentation is as follows:

Nevus of Ota

Nevus of Ota is an oculodermal melanocytosis affecting approximately 0.6% of the Asian population at birth or developing in their teens. Clinically, it presents as a bluish-black hyperpigmentation along the ophthalmic or maxillary branches of the trigeminal nerve. QS lasers, including QS ruby, QS alexandrite, and QS 1064 nm Nd : YAG, have all been used to achieve good therapeutic results.Watanabe and Takahashi looked at 114 nevus of Ota patients treated with QS Ruby and reported a good to excellent degree of lightening after three or more sessions. Kono et al confirmed the findings when he reviewed 101 nevus of Ota patients treated with QS Ruby and reported 56% achieving 75% improvement, and 36% achieving complete clearing. Hypopigmentation was seen in 17% of patients and hyperpigmentation in 6%. Studies comparing the use of QS alexandrite and QS 1064 nm Nd : YAG found the former better tolerated but the latter more effective after three or more treatment sessions. The longer wavelength of the QS Nd : YAG targets dermal pigment effectively with minimal epidermal damage in darker skinned individuals (Fig. 10.3). More recently, fractionated laser technology has been added to the currently available options. Near-complete clearance of a case of nevus of Ota after serial therapy using 1064 nm QS Nd : YAG, followed by 1550 nm non-ablative fractionated erbium-doped fiber laser treatments at 2-month intervals; and a further case achieving complete clearance with sequential same day therapy with the same devices have been reported. Treatment of nevus of Ota at a younger age requires fewer treatment sessions and is associated with fewer complications compared with older patients, and early treatment is therefore recommended (see Case study 2). It is important to note that the risk of recurrence is estimated to be between 0.6% and 1.2%⁸, which has important implications particularly when counseling pediatric patients.

Figure 10.3 (A) Nevus of Ota at baseline and (B) after six treatments with QS 1064 nm Nd : YAG laser; treatment parameters: 12 J/cm², 10 Hz, 2 mm.

Hori’s macules or acquired bilateral nevus of Ota-like macules

Hori’s macules (ABNOM) affect 0.8% of the Asian population and presents in late adulthood as bluish brown dermal hyperpigmentation typically affecting the bilateral malar regions, forehead and temples of middle aged women, without any mucosal involvement. QS lasers such as QS ruby, QS alexandrite and QS 1064 nm Nd : YAG have been found to be effective in the treatment of Hori’s macules. More recent studies also support these results. Kagami et al reported the efficacy of QS alexandrite in 24 Japanese patients, with 45.8% reporting greater than 50% improvement. Cho et al also evaluated the use of 1064 nm QS Nd : YAG at low fluences in 15 patients, 80% of whom had greater than 50% improvement. From our experience, Hori’s macules tend to be more resistant to treatment than nevus of Ota. Shorter treatment intervals every 4 weeks tend to yield better results. Combination treatment with QS 532 nm Nd : YAG, followed by QS 1064 nm Nd : YAG has also been found to be more effective than the 1064 nm wavelength alone. Transient PIH is a common adverse event, occurring in the majority of treated patients (Fig. 10.4). Permanent hypopigmentation has been reported after QS ruby treatment. In order to reduce the risk of PIH, all patients should be given pre and post-treatment bleaching agents (see Case study 3).

Figure 10.4 (A) Hori’s macules before QS ruby treatment and (B) PIH post QS ruby treatment.

Hair removal

Pigment-specific lasers with longer wavelengths, longer pulse durations and concomitant epidermal cooling have been successfully employed for hair removal in darkly pigmented skin. LP alexandrite laser, 810 nm diode, and 1064 nm Nd : YAG lasers can all be safely applied with few side effects. A recent split axilla comparison study by Wanitphakdeedecha and co-workers showed that, although both high-fluence, low-repetition 1064 nm Nd : YAG and low-fluence, high-repetition 810 nm diode laser were successful in axillary hair removal, results with the Nd : YAG were better. However, the diode laser was less painful. The use of pneumatic skin flattening has also been explored as a viable alternative to dynamic cooling device, in the reduction of pain during axillary hair removal.

Becker’s nevus

Becker’s nevus commonly presents as a brown irregular patch accompanied by dark, coarse hair. It usually appears in adolescence and in males. Histologically, increased melanin is seen in the basal cells, and melanophages may be present in the papillary dermis. It is a benign condition with no reports of malignant transformation. Previously, lasers such as QS ruby and QS Nd : YAG have been shown to improve such lesions. A comparative study of the two devices showed mean clearance of at least 43% after a single treatment with either laser. Trelles et al later compared the use of Er : YAG laser and QS 1064 nm Nd : YAG in 22 patients. At 2 years’ follow-up, 54% of patients (n = 6) achieved complete clearance after a single treatment with Er : YAG, compared with just 1 out of 11 patients reporting clearance after three treatment sessions of Nd : YAG laser. Although clinically effective, ablative laser carries a high risk of adverse effects, especially in darker skin types. QS lasers rarely achieve complete clearance, and multiple treatments are necessary. More recently, fractional resurfacing has been suggested by Glaich and colleagues as a promising new treatment modality, with two cases reporting at least 75% pigment reduction after five to six treatments with 1550 nm erbium-doped fiber laser at 4-week intervals. Long-pulsed pigment lasers have also been employed successfully to target both pigment and hair in Becker’s nevus. In our experience, LP alexandrite (20–35 J/cm², 10 mm spot size, pulse duration 1.5 ms) gives a 50% success rate after four to eight treatments. Possible side effects include scarring and hypopigmentation. Long-pulsed pigment laser together with non-ablative fractional resurfacing with 1927 nm thulium fiber laser can lead to an optimal outcome (see Case study 4).

Melasma

Melasma is a common acquired symmetrical hypermelanosis involving sun-exposed areas commonly seen in Asian middle-aged women. Genetics, UV radiation, pregnancy, and hormonal therapies are all thought to be contributing etiological factors and it remains a challenging condition to treat. Increased pigment can be seen in either the epidermis (brownish black), or dermis (bluish gray), or both. There may also be some overlap between dermal melasma and Hori’s macules (ABNOM). Wood’s lamp can be useful in differentiating between the skin layers, with the pigmented epidermal layer demonstrating increased reflectance, in contrast to a lack of reflectance from the pigmented dermal layer.

In addition to sun protection and avoidance of aggravating factors such as oral contraceptives, bleaching agents remain the mainstay of treatment for melasma. Combinations of hydroquinone with topical corticosteroids and tretinoin are effective as first-line treatment. Other bleaching agents used include azelaic acid, kojic acid, arbutin, and licorice extract. Their mechanism of action includes tyrosinase inhibition, suppression of the secretory function of melanocytes, decreasing rate of transfer of melanin from melanosomes to keratinocytes, and increased epidermal turnover. Chemical peels and microdermabrasion are also useful adjuncts to topical treatments in the management of melasma in Asians.

Although laser therapy has been used to improve melasma, caution must be exercised as worsening of the disease or PIH may occur after treatment. This is likely to be due to the pathogenesis of melasma, which is believed to be due to increased activity of melanogenic enzymes, resulting in hyperactive melanocytes. Sublethal laser damage to these labile melanocytes is thought to result in an increase in melanin production and hyperpigmentation. Laser therapy should therefore be considered as second-line treatment for patients who have not improved sufficiently after 3–6 months of topical treatment.

Wang’s group in Taipei examined patients with melasma treated with IPL and found a significant improvement of 39.8% in the IPL group compared with 11.6% in the control. Two patients developed transient PIH, and partial repigmentation was noted after 24 weeks, suggesting the need for repeated treatments for maintenance. They suggested the lowest fluence to achieve minimal erythema be used, which supported findings by Negishi’s group. This is to avoid excessive thermal damage to labile melanocytes, which may lead to inflammation and subsequent PIH.

Pigment lasers have also been used to treat melasma. Low fluence, large spot size, multiple pass QS 1064 nm Nd : YAG, sometimes referred to as laser toning or laser facial, has become increasingly popular for the treatment of melasma. Some studies have reported it to be effective and safe, while others have highlighted important complications. Zhou et al published a recent study examining 50 patients with melasma treated with 9 weekly sessions, and reported 70% with more than 50% reduction in melasma area and severity index (MASI) values, and 10% with complete clearance. However, the recurrence rate at 3 months was 64%. Promising results were similarly reported in a prospective study by Polnikorn, after 10 weekly sessions of 1064 nm Nd : YAG in 35 refractory melasma cases. Recurrence at 6 months was seen in two cases. In addition, he noted mottled hypopigmentation occurring in three patients. Facial depigmentation is an increasingly recognized phenomenon often encountered with frequent treatments with QS 1064 nm Nd : YAG (Fig. 10. 5). Chan et al reported it in 14 Chinese patients, after a variable number of such treatments. Wattanakrai et al and Cho et al also described a similar adverse effect occurring after 1 to 2 weekly treatments with this laser for melasma, with 13.6% and 8% rate of hypopigmentation reported, respectively. With risks of recurrence and punctate hypopigmentation post-laser treatment, patients need to be adequately informed of potential complications prior to embarking on such treatments for melasma. Optimal parameters from future studies will be helpful.

Figure 10.5 (A) Cross-polarized and (B) UV images of depigmented macules after 20 sessions of QS 1064 nm Nd : YAG laser treatment.

Ablative resurfacing has been used with some success for the treatment of melasma. A Thai study showed promising results using variable square pulse erbium : yttrium aluminum garnet (Er : YAG) laser resurfacing in 20 patients. However, 17.6% experienced transient PIH, and recurrence was observed after the treatment was discontinued. Fractional resurfacing has been explored as a better option, with ‘melanin shuttling’ of underlying dermal pigment coupled with remodeling of the underlying pathologic dermis proposed as a possible mechanism. Rokhsar & Fitzpatrick piloted the use of fractional resurfacing in 10 patients, and demonstrated 60% achieved 75–100% improvement, and 30% had less than 25% improvement when treated at 1–2-week intervals for four to six treatments. A Korean study by Lee et al later showed more limited efficacy, with 60% of 25 patients reporting improvement in melasma after 4 monthly sessions, and improvement declining to 52.2% at 6 months; 13% of patients developed hyperpigmentation.

Due to limitations of recurrence, hyper- and hypopigmentation post-laser treatment, topical treatments remain the first line treatment for melasma, and laser treatment should only be used with caution, especially in ethnic skin.

Post-inflammatory hyperpigmentation (PIH)

PIH is characterized by an acquired increase in pigmentation secondary to an inflammatory process, and is a commonly observed response to cutaneous injury in melanin-rich Asian skin. The severity of PIH is related to the degree of inflammation and extent of disruption of the dermo-epidermal junction. Such melanogenesis is increased the darker the skin types. Histologically, excess epidermal and dermal pigmentation can be seen.

Although a benign condition, PIH can cause significant anxiety and lowered self-esteem in patients. Its initial management involves early and effective treatment of the underlying skin condition, in order to minimize any inflammation that may cause further PIH. All potential irritants such as fragrance or cosmeceuticals should be stopped. Photoprotection is imperative. Treatment modalities to accelerate the normalization of skin color include topical agents such as hydroquinone, retinoids, azelaic acid, kojic acid, glycolic and lactic acid, chemical peels, microdermabrasion, and laser treatment.

Different lasers have been used to improve PIH. Vascular lasers, such as the 595 nm LPDL, target mainly oxyhemoglobin, and can be used to treat the vascular component of the inflammatory process. When used with compression, Kono and colleagues reported that it can also be effective for pigment removal. QS lasers, such as QS Nd : YAG and QS alexandrite, have long been successfully used to treat cutaneous pigmentation. Depending on the wavelength used, epidermal and dermal pigmentation can be targeted accordingly. In recalcitrant PIH where dermal pigment may be present, 1064 nm QS Nd : YAG has been successfully used in previous reports with minimal adverse effects. More recently, our group examined the management of acne PIH in Chinese patients, and suggested the use of bleaching agents for the initial 3 months, followed by combination topical and laser therapy (LPDL and / or 1064 nm QS Nd : YAG) for recalcitrant PIH with vascular and dermal components (Fig. 10.6). Laser treatment in itself can of course be a cause of PIH in darker skin types, and strategies to reduce PIH risk include effective sun protection pre- and post-procedure, the use of long-pulsed lasers, cooling, diascopy, and small spot sizes in this group.

Figure 10.6 Management of acne PIH with different treatments: (A) 2 months after azelaic acid 20% + Mometasone 0.1% cream + hydroquinone 4% cream. (B) After five treatments with QS1064 nm Nd : YAG; treatment parameters: 3.1 J/cm², 8 mm, 10 Hz.

Melanocytic nevi

Although the gold standard for the removal of melanocytic nevi is by excision followed by histological examination, the resulting scar is often an undesired cosmetic outcome. Lasers have been used successfully to remove and lighten nevi with better cosmetic results. However, the clinician needs to be aware of the potential risk of malignant transformation, and the patient’s skin type, family history, and location of lesion are important considerations. Incidence of melanoma has been reported to be between 0.2 and 2.2 per 100 000 in Asians, depending on skin type. Acral regions, such as the feet, appear to be more commonly affected. Laser treatment of melanocytic nevi may therefore be considered in darker-skinned individuals with no risk factors, and lesions in a non-acral location, after an explanation of the risks involved. The combination of CO₂ and QS alexandrite laser was reported to be successful in 11 patients with congenital nevi. Further studies reported the successful use of QS ruby laser and normal mode ruby laser for acquired melanocytic nevi, particularly for flat lesions. Some compound lesions demonstrate only partial response. The use of fractional resurfacing has now been incorporated into the treatment regimen.

A typical treatment protocol is as follows: long-pulsed pigment laser (LP alexandrite 755 nm, 3 ms, 10 mm spot size, 15–25 J/cm² depending on the degree of pigmentation with slight dark gray appearance being the endpoint), to be followed immediately by QS ruby laser (4 mm spot size, 3–4 J/cm² with immediate whitening as the end point). 4–6 weeks later, the patient will be treated with non-ablative fractional resurfacing using a combination of 1550 nm and 1927 nm wavelengths (1550 nm, 4 passes, 50 mJ, treatment level 10, to be followed by 1927 nm, 4 passes, 20 mJ, treatment level 10). Such alternate treatment at 4–6 weekly intervals is performed until the nevi completely lighten (see Case study 5).