Melasma is a common disorder of hyperpigmentation more common in women with Fitzpatrick skin phototypes III or higher. It typically appears in sun-exposed areas as a light to dark brown, irregular hypermelanotic macules and confluent patches. Histologically melasma lesions show a higher degree of ultraviolet induced damage such as solar elastosis and damaged basal membrane as well as increased vascularity.1–4 Although many treatment options are available including topical depigmenting agents, coherent and non-coherent photothermolysis, chemical peels, and oral agents, the treatment of melasma remains challenging.5

Since 2008, low-fluence Q-switched Nd:YAG laser (LFQSNY) and topical lightening agents (TLA) has become one of popular treatments.6 LFQSNY, also known as laser toning is believed to interfere with melanosome transfer and damage stage IV melanosome by subcellular-selective photothermolysis.7 Although studies confirm substantial and long term therapeutic benefit of this treatment method,8 there are melasma that is resistant to LFQSNY. Here, we report five cases where melasma resistant to LFQSNY/TLA responded favorably to a modified LFQSNY/TLA with the addition to invasive micro-pulsed electric signed device (IMPES).

Five patients whose melasma were not responding to a standard LFQSNY/TLA were treated with an addition of IMPES (Sylfirm, SLR Inc., CA, USA) to their existing LFQSNY/TLA treatment regime (Table 1). At the time of study enrollment, all five patients had already received more than six sessions of LFQSNY combined with daily TLA use. However, patients’ melasma stopped improving or failed to improve at least over 3 sessions (3 weeks) or longer period of time, based on both physician global assessment and patient self-assessment. All patients were female with Fitzpatrick skin types III–IV and aged between 42 and 53 years (mean: 48 years). Informed consent was obtained and the study protocol was in accordance with the guidelines of the 1975 Declaration of Helsinki. Patients received five to seven weekly sessions of LFQSNY/TLA/IMPES combination.

The face was cleansed with gentle cleanser. A topical eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA; AstraZeneca Canada Inc., Ontario, Canada) was applied to lesional areas under occlusion for 30 minutes. Immediately upon removal of EMLA, LFQSNY (Helios II, LaserOptek Co. Ltd., Kyunggi, South Korea) was used to paint the entire face at the following settings: fluence 1.89 J/cm², a spot size of 8 mm, a repetition rate of 10 Hz, <10% overlap, and the end-point of mild erythema. IMPES treatment was immediately followed: a power levels ranged from 3 to 5, penetration depth 1.2 mm to 1.7 mm, single pass, and <10% overlap. All patients were asked to continue with their existing topical medications and sun protection routine.

Digital photographs were taken at the study enrollment and 1 week after the last treatment session. Clinical improvement scores were determined by the treating physician based on pre and post treatment photographs using tertile grading scale: 1–33%, minimal clearance; 34–66%, moderate clearance; 67–100%, marked clearance. Based on pre- and post-treatment photographs, moderate to marked improvement was observed in all five patients (Table 2, Fig. 1–3). In addition, a reduction of pore sizes and an increase of skin’s textural homogeneity were observed. Patients reported mild to moderate pain at the time of IMPES treatment. Mild erythema and edema was noted post-treatment, which resolved within several hours. No adverse events including a formation of scabs were reported.

Here, we report five cases of resistant melasma that were successfully treated with an addition of IMPES to patients’ existing treatment regime. To our knowledge, the present study is the first reported cases of melasma treated successfully with an IMPES. IMPES’s system delivers a signal intradermally via penetrating electrodes. Previously, multiple studies on fractional lasers have demonstrated lightening of melasma. This method is believed to improve melasma by increasing transepidermal elimination of melanin and elastotic dermal content of solar elastosis.9–11 However, due to limited therapeutic benefit,12,13 high rate of complications,8 and long-term risk of hyperpigmentation,14 fractional photothermolysis is currently considered a third-line treatment.5 Fractional laser systems unleash the most damage to the skin surface and lesser in dermis. As a result, delivering a high energy to deep dermis without causing a significant damage to epidermis and epidermaldermal junction is impossible. The damage to epidermis may lead to stimulation of melanocytes with subsequent post-inflammatory hyperpigmentation. In addition, a significant fractional photothermolysis of epidermaldermal junction can worsen melanin incontinence by weakening basal membrane.15 A comparative study failed to show additional benefit of adding fractional photothermolysis to LFQSNY treatment for the purpose of treating melasma.16

The exact mechanism by which IMPES improved melasma is not investigated in our study. In many fractional laser studies have considered transepidermal elimination of melanin as the primary mode of action. However, skin treated with IMPES did not show any obvious micro-crusting or increased epidermal shedding. An experiment of non-insulated penetrating electrode placed in soft tissue of relatively uniform electrical impedance showed that under certain settings, thermal coagulation can be limited to the tip of the electrode and made to expand to the entire length of the needle by increasing energy.17 It is known that radio frequency current from the needle electrodes placed in epidermis and dermis preferentially travels through tissues of higher electrical conductivity. Epidermis is known to exhibit greater electrical resistance.18 The higher water content and presence of vasculature confer higher conductivity in the dermis. Therefore under certain conditions, non-insulated penetrating needle electrodes may deliver radio frequency energy almost exclusively to dermis without significant damage to overlying structures such as epidermis and basal membrane. A study of insulated needle electrodes radio frequency device shows that an increased number of fibroblasts including alteration of micro-environment were found after deep dermal heating.19

We speculate that the IMPES may work through different modes of action including enhancing permeability of TLA, increasing degradation of dermal vasculature, and reversing a number of known histological changes associated with melasma. The therapeutic effects of TLA are known to be limited by their poor transdermal penetration. A study with non-energized multiple micro-needles demonstrated that methylene blue dye used in the experiment penetrated both epidermis and dermis through vertical epidermodermal fissure created by microneedle treatment.20 In addition, the delivery of anti-melanogenic agents via microneedling is reported to be an effective treatment method for melasma.21 Similarly, micro-channels created by IMPES’ needle electrodes may lead to enhanced transdermal drug delivery, thus improving their anti-melanogenesis effects of the TLA used by the patients. A number of studies showed increased vascularization, melanin incontinence, and solar elastosis in lesional skin of melasma. Although the role of the vascularization in melasma is still yet to be understood, studies demonstrated that therapies targeting the vascularization can lead to improvement of melasma.22,23 The higher electric conductivity of vasculature may preferentially induce dermal vasculature to be coagulated before coagulating epidermis and dermis by IMPES. Fibroblasts in the dermis are able to secrete pro-melanogenesis paracrine factors such as IL-1α, ET-1, ET-3, SCF, growth related oncogene-α, c-Kit, GM-CSF, hepatocyte growth factor, and prostaglandin-2 depending on the conditions of their micro-environment. Previous studies have shown that bipolar fractional radio frequency treatment can reverse solar elastosis by inducing neoelastogenesis and neocollagenesis.24 Alteration of micro-environment caused by the reversal of solar elastosis with IMPES may alter the paracrine behavior fibroblasts. Reduction of the pro-melanogenesis paracrine factors in the lesional skin may potentially lead to decreased melanogenesis, thus lightening of melasma.

Although many therapies of various therapeutic efficacies exist today, the treatment of melasma has been challenging. In our patients with resistant melasma, the IMPES treatments were found to be an effective adjunctive treatment option, resulting in clinical improvement of melasma which was previously refractory to standard LFQSNY and TLA. Future studies should include histological evaluation to elucidate possible therapeutic mechanisms and long-term follow-up to monitor for recurrence.