A retrospective study of 1064‐nm Q‐switched Nd:YAG laser therapy for acquired bilateral nevus of Ota‐like macules

Abstract Background The therapeutic efficacy of laser treatments for acquired bilateral nevus of Ota‐like macules (ABNOM) varies among studies, and few studies have evaluated the factors affecting therapeutic effects. Aims To evaluate the efficacy and safety of 1064‐nm Q‐switched Nd:YAG laser (QSNYL) therapy for ABNOM and to identify the factors influencing the outcome. Methods A total of 110 patients with ABNOM were retrospectively evaluated and received two‐to‐nine treatment sessions. The effects of different factors on the therapeutic effect were analyzed on the basis of the number of treatments, age at first treatment, skin type, lesion color, affected area, number of lesion sites, and presence of concomitant melasma. Results The curative effect was positively correlated with the treatment time and negatively correlated with the increasing age at first treatment (p < 0.05). The curative effect was better in patients with skin type III than those with type IV ( p < 0.05) and in patients with a lesion area of less than 10 cm2 than those with a larger affected area (p < 0.05). Additionally, the treatment effect was poorer in patients with concomitant melasma (p < 0.05). The treatment effect was not significantly correlated with the lesion color or number of affected sites (p > 0.05). Eleven patients (10%) developed postinflammatory hyperpigmentation (PIH). Conclusions Early and repeated QSNYL therapy achieved satisfactory results for ABNOM. The risk of PIH after laser treatment is highest among patients with older age, darker lesion color, and darker skin color. For patients with ABNOM with concurrent melasma, low‐energy laser therapy is recommended to reduce the risk of melasma aggravation.


INTRODUCTION
Acquired bilateral nevus of Ota-like macules (ABNOM) was previously considered to be a variant of nevus of Ota. 1 ABNOM often occurs in the zygomatic region and is also called nevus fusco-caeruleus zygomaticus. 2 As an acquired disease, ABNOM is more common in Asian women older than 20 years. Most cases are bilaterally symmetric and do not involve mucosa. Histopathological examination shows slender, pigment-bearing cells dispersed in the middle and upper parts of the dermis, with some melanocytes distributed in the perivascular area. [1][2][3] Various types of lasers have been used to treat ABNOM, including the Q-switched ruby laser (QSRL), 4 Q-switched alexandrite laser (QSAL), 5-8 Q-switched Nd:YAG laser (QSNYL), [9][10][11][12][13] and picosecond alexandrite laser (PSAL). 14 QSRL is an effective and less invasive tool for the eradication of NFZ. But it has the risk of long-term hypopigmentation. 4 After QSAL treatment, there is a high probability of erythema and hyperpigmentation or hypopigmentation. 5 Yu et al. showed that PSAL seems to have better efficacy and safety than QSAL, but there are few studies on the treatment of ABNOM with PSAL, which needs further discussion. 14 Epidermal pigmented lesions respond best to 532-nm QSNYL with shorter wavelengths.
ABNOM, as a dermal pigmented lesion, has not been reported to be treated with 532-nm QSNYL alone. Compared with other lasers, the 1064-nm QSNYL has a longer wavelength and selectively targets deeper tissues, and it has poor absorption in epidermal melanin, making it relatively safe for people with dark skin. 15 Although several studies have evaluated the 1064-nm QSNYL in the treatment of ABNOM, the treatment effect is inconsistent and the related factors affecting the efficacy are also controversial. To improve the efficacy and optimize the treatment strategy, we retrospectively analyzed the factors affecting the results of 1064-nm QSNYL therapy for ABNOM.

Patients
All patients with ABNOM who underwent at least two treatments with 1064-nm QSNYL alone in the Department of Laser and Aes-

Treatments
Before treatment, each patient's face was cleaned and photographed
ABNOM lesions were assessed by two plastic surgeons who were not involved in the treatment. When the two assessors reported different improvement scores for a given lesion, the lower of the two scores was used. Any adverse effect such as erythema, pigmentary changes, or scarring was recorded.

Statistical analysis
Statistical analysis was performed using SPSS version 26.0. The Mantel-Haenszel χ 2 test was used to determine whether there was a linear relationship between two factors. The predictors were lesion color, area, number of lesion sites, and combined melasma; the outcome measure was age. The χ 2 test was also used to identify the factors affecting PIH. The univariate analysis (χ 2 test) and multivariate logistic regression analysis were used to analyze the factors affecting the efficacy of 1064-nm QSNYL therapy in the treatment of ABNOM. Variables with p < 0.10 in univariate analysis were included in the model for stepwise multivariate logistic regression analysis, and a two-sided p value of <0.05 was considered statistically significant.

Patient characteristics
A total of 110 patients with ABNOM were included (108 females and 2 males). According to the characteristics of the onset age of ABNOM and melasma, the age is divided into 20 years or younger, 21-29 years, and 30 years or older. The patient characteristics are summarized in Table 2. The zygomatic region was affected in all 110 patients. Lesion color was positively correlated with age (χ 2 = 32.411, p < 0.001); as the patient age increased, the lesions gradually became gray ( Figure 1A).

Clinical efficacy
Among the 110 patients, the good to excellent clearance rates were 28.1%, 50%, 70%, and 92.3% in the patients treated twice, three times, four times, and five or more times, respectively ( Figure   curative effect was better in patients with a lesion area of less than or equal to 10 cm 2 than those with larger lesion areas (p < 0.05) and was better in patients without melasma than in those with melasma (odds ratio: 5.940, 95% confidence interval 1.620-21.786, p < 0.05) (Table 3). However, the color and number of lesions did not significantly affect the treatment effect (p > 0.05) ( Table 3). In addition, we further analyzed the relationship between the age of first treatment and the number of treatments to find a potential correlation, and the results showed that the number of treatments was not affected by age (p > 0.05).

Adverse reactions
There were no serious adverse reactions during treatment. After treatment, some patients developed temporary mild erythema and edema. No patients developed scarring after treatment. Eleven  Table 4). The risk of PIH after laser treatment increased with age and was increased in patients with skin type IV and darker lesions (p < 0.05). PIH disappeared within 6 months after laser treatment. There were 18 (16.4%) patients with ABNOM who initially had melasma; after laser treatment, 6 (33.3%) had hyperpigmentation, whereas 9 (50%) had aggravation of the original melasma ( Figure 5).
The continuous correction χ 2 test showed that patients with melasma were significantly more likely to have PIH than those without melasma (33.3% vs. 5.4%, p < 0.05).

DISCUSSION
ABNOM is a common dermal melanocytic hyperpigmentation that was first reported in 1984 and is also called Hori's nevus. 1 The lesions in ABNOM are round, oval, and polygonal, with clear boundaries. They are mainly distributed in the bilateral zygomatic regions but may also involve the forehead, temporal area, eyelids, and root or alae of the nose 1,2 ; the skin above the upper lip is involved in some cases. 16 Patients with ABNOM have brown, blue-brown, or slate-gray macules.
Our study showed that as the patient age increased, the lesion color gradually deepened and the number of lesion sites increased, which is in agreeance with the findings of previous studies. 17 Previous studies have shown that ABNOM often occurs after the age of 20 years, but there are also reported cases of ABNOM onset in children aged 9 3 and 6 years. 16 One of our patients was only 5-year old at the time of first presentation at our hospital for treatment ( Figure 6).
The etiology of ABNOM is still unclear, but the mechanism is likely to be activation of preexisting dermal melanocytes. 18,19 The potential activators are sun (ultraviolet) exposure, 2,18,20 inflammatory reaction, 3,19 and changes in sex hormone concentrations. 16,18,21 In our study cohort, there were far more women with ABNOM than men, especially women older than 20 years, which suggests that estrogen plays a role in the development of ABNOM. The association between ABNOM and estrogen was further suggested by the high incidence of melasma induced by laser therapy in our cohort.
Our study evaluated the safety and efficacy of 1064-nm QSNYL treatment among 110 patients with ABNOM on the basis of the age at first treatment, number of treatments, skin type, lesion color, affected area, number of lesions, and presence of concomitant melasma. The present results showed that the therapeutic effect was related to the number of treatments, age at first treatment, skin type, and lesion area. However, the therapeutic effect was not correlated with lesion color or number of lesion sites. The treatment effect was best in younger patients with a lesion area of less than 10 cm 2 . Previous studies have shown that melanin remains in the exposed area even after laser pulses destroy dermal melanocytes, as the lesion area only lightens after the melanin is engulfed by macrophages and is removed to lymph nodes or other parts. [22] As the patient age increased, the Note: Asterisks indicate statistical significance (p < 0.05). Abbreviations: ABNOM, acquired bilateral nevus of Ota-like macules; CI, confidence interval; OR, odds ratio.
lesion area increased and the lesions tended to fuse and darken, which means that the dermal melanin in the lesions increased. We speculate that this situation increases the burden of macrophages to remove melanin after laser treatment, preventing all melanin damaged by laser irradiation from being transported to lymph nodes. Therefore, additional treatment may be required. In addition, our study showed that with increasing age, patients with ABNOM had an increased risk of concomitant melasma and the lesion color tended to darken; both of these factors increase the risk of PIH, which increases the difficulty of treatment and reduces the curative effect. Therefore, to achieve a good therapeutic effect, we suggest that ABNOM should be actively treated in the early stage.
PIH is a frequent problem after laser therapy and is much more problematic in dark-skinned patients with ABNOM than in those with light skin. 5,9,10 In our study, patients with skin type inned patients with ABNOM than. PIH increases the patient's psychological burden, reduces their satisfaction with treatment, and affects their confidence  were also advised to moisturize and strengthen sunscreen measures.
The incidence of PIH after laser treatment in our study was 10%, which is less than the incidence of 50% and 100% in previously reported. 9,10 This is inseparable from strengthening the evaluation of patients' condition before laser treatment and selecting appropriate energy density.
In our study cohort, PIH subsided spontaneously within 3-6 months in all affected patients. Oral vitamin C and topical hydroquinone cream were applied to accelerate the regression of pigmentation. The laser treatment was continued after the PIH disappeared.
Our study found that the melasma worsened after treatment in 9 Oral tranexamic acid is usually recommended, and laser irradiation is not performed in areas with melasma.
Our study has some limitations. It was a retrospective study with the limitations of a small sample size and lack of objective evaluation.
Future large-scale prospective studies are warranted to evaluate the effectiveness and safety of QSNYL therapy for ABNOM.

CONCLUSION
ABNOM occurs more frequently in women than in men and is effectively and safely treated with 1064-nm QSNYL therapy. Earlier initiation of laser treatment achieves a better treatment effect, and the curative effect is better in patients with an affected area of less than 10 cm 2 . The risk of PIH after laser treatment is highest in patients with older age, darker lesion color, and darker skin color. Patients with melasma have a poor curative effect and are prone to PIH and melasma aggravation. For such patients, we recommend using a lower energy for laser treatment.