Summary
This article presents a protocol to conduct the treatment of melasma by using roller microneedles in combination with tranexamic acid solution and evaluate the efficacy.
Abstract
Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective management. The precise underlying causes of melasma remain elusive, and the current therapeutic approaches predominantly encompass pharmaceutical and laser interventions, with limited efficacy. Transdermal administration stands as a prevalent treatment method for melasma, often facilitated by the application of microneedles. Among these, tranexamic acid emerges as a frequently employed therapeutic agent. A subset of microneedles, known as roller microneedles, plays a significant role in this approach by delicately puncturing the epidermis with multiple fine needles, synergizing with drug delivery. This methodology not only enhances drug absorption but also augments treatment efficacy while minimizing tissue trauma. These attributes forecast promising avenues for the treatment of melasma. This article primarily introduces the combination of roller microneedle and tranexamic acid solution in the treatment of melasma and demonstrates the efficacy of roller microneedle and tranexamic acid solution in the treatment of melasma through clinical cases.
Introduction
Melasma, also known as chloasma, is a chronic and acquired facial hyperpigmentation skin condition. Clinically, it presents as symmetrical, light to dark brown patches with unclear borders, distributed on the cheeks, forehead, and jawline. The incidence rate among Asian women of childbearing age can be as high as 30%1. The disease is easily diagnosed but difficult to cure. The pathogenesis of melasma is not yet fully understood, but three main factors contribute to its development: genetic susceptibility, exposure to sunlight, and hormonal changes. Increased melanin synthesis, vascular proliferation at the site of skin lesions, inflammatory reactions, and impaired skin barrier function all play a role in the occurrence of melasma2.
Currently, treatment options for melasma include laser therapy and medications, among which, transdermal administration is a widely used method. However, the main challenge lies in the barrier function of the stratum corneum, which hinders drug penetration. Microneedle therapy creates multiple micro-channels in the skin within a short period, disrupting the stratum corneum, inducing collagen production, and increasing skin permeability. This approach holds promise in allowing drugs to diffuse into the skin and then rapidly reseal, thus avoiding the introduction of toxic or irritating substances3.
Commonly used microneedle tools include the electronic water light injection microneedle, roller microneedle, electrically assisted nanocrystalline microneedle, plum blossom microneedle, and single needle microneedle4. The roller microneedle is characterized by less trauma, good curative effect, convenient operation, and can be combined with some other drugs to treat melasma. It has a good therapeutic prospect for melasma and is worth more promotion and use in clinical practice. This article introduces the operation and precautions of roller microneedles combined with tranexamic acid in the treatment of melasma and demonstrates the efficacy of roller microneedle combined with tranexamic acid in the treatment of melasma through clinical cases.
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Protocol
All research procedures involving human participants comply with the ethical standards of the Ethics Committee of Chongqing Hospital of Traditional Chinese Medicine and the principles of the Declaration of Helsinki (1964) and its subsequent amendments and have received approval for the study from the aforementioned Ethics Committee. Image data collection was performed with both verbal and written consent from the patients, and photographs taken for teaching purposes as a routine part of the examination were obtained using the Multispectral Dermoscope.
1. Patient selection
- Set the following inclusion criteria5:
- Select patients based on the presence of facial light to dark brown, well-defined patches, typically with symmetrical distribution, absence of inflammation, and scaling.
- Select patients based on the absence of significant subjective symptoms such as itching, burning, and pain.
- Select patients considering that melasma predominantly occurs in females, primarily after puberty.
- While selecting patients, consider seasonal variations in the condition-often worse in summer and milder in winter.
- Exclude patients if other conditions (such as nevus fuscoceruleus zygomaticus, Riehl's melanosis, and pigmentary photodermatitis) that may cause hyperpigmentation are present.
2. Preparation for roller microneedle treatment
- Preoperative communication
- Understand the patient's treatment goals and cosmetic aspirations and gather complete medical history, including medication history, allergies, contraindications, and past cosmetic treatments.
- Inform the patients about the treatment's effects, steps, potential complications, recovery time, duration, and costs. Discuss specific treatment plans and alternative options to ensure all patient queries are addressed, helping them establish realistic expectations and achieve higher satisfaction.
- Ask patients to sign an informed consent form.
- Environmental requirements
- Set aside a quiet, well-lit treatment room for the operation of the roller microneedle and disinfect it for 30 min with ultraviolet light before the procedure.
- Ask the patients to wear shoe covers and hats upon entering the treatment room.
- Preparation of the necessary items and medication for treatment
- Check and prepare all the materials listed in the Table of Materials.
- Makeup removal and cleansing
- If the treatment area was covered with makeup, thoroughly remove it with makeup remover before cleansing.
- For non-makeup wearers, clean the treatment area with a gentle cleansing product.
- Multispectral dermatoscopy recording
NOTE: The Multispectral dermoscope uses different light sources to capture facial ultra-high pixel images.- Prior to treatments and after three treatments, use the Multispectral dermoscope to take photos of the patient's front, left (45°), and right (45°) from three different angles and record the values of patients' UV-shallow and -deep spots and brown spots
- Application of topical anesthesia
- Apply 5% lidocaine cream evenly to the treated area, with a total dosage of 30-40 g, and wrap it with cling film to enhance the anesthesia effect for 40-60 min.
NOTE: Some patients may exhibit symptoms of allergy to the topical anesthetic. Patients may experience severe itching, burning, or stinging at the site of application. If such reactions occur, promptly remove the anesthesia and provide appropriate symptomatic treatment. - Before the next treatment, ensure proper moisturization of the skin in the anesthesia application area.
- Apply 5% lidocaine cream evenly to the treated area, with a total dosage of 30-40 g, and wrap it with cling film to enhance the anesthesia effect for 40-60 min.
- Preparation of microneedle solution
- Extract 5 mL of 5% tranexamic acid solution using a syringe and set it aside for use.
- Preparation of microneedle instruments
- Select a 0.5 mm roller microneedle (Figure 1) and soak it in 0.1% benzalkonium bromide solution for approximately 20 min to disinfect it.
- Rinse the microneedle 3x with physiological saline to remove the disinfectant.
NOTE: Avoid cross-contamination by using a single roller microneedle for each patient to prevent unnecessary damage to the skin due to blunt needles and to prevent the spread of diseases between patients.
- Removal of topical anesthesia
- After a sufficient duration of topical anesthesia application, remove the cling film and scrape off the anesthetic with a spatula. Use gauze soaked in 0.9% saline solution to wipe off any remaining anesthetic from the face.
- Disinfection
- Expose the treatment area, wrap the hair with a disinfectant towel when treating the face, and disinfect the facial skin with a 0.1% benzalkonium bromide cotton ball 3x from the top to the hairline edge, to the lower jaw edge, and chin, following the principle of "bottom-up, inward-outward" to prevent infection.
3. Roller microneedle procedure
- Have the therapist wash their hands and wear a hat, mask, and sterile gloves.
- After informing the patient about beginning the procedure, instruct the patient to close their eyes and treat in the order of left cheek, right cheek, forehead, jaw, upper lip, and nose. Inject an appropriate amount of tranexamic acid solution onto the skin using a syringe, apply evenly by hand, and then rinse the roller microneedle with physiological saline, roll it in a short distance along the horizontal, vertical, and oblique directions in the treatment area.
- Gradually perform the treatment in different areas, applying the solution while rolling to enhance absorption. Repeat 3-5x in one area, preferably with skin flushing and no obvious bleeding. Apply force evenly, neither too heavy nor too light, and do not drag a microneedle on the skin.
4. Efficacy evaluation
- Use a combination of roller microneedles and topical tranexamic acid solution 3x for the treatment of melasma, once every 4 weeks, as a course of treatment.
- Use the multispectral dermatoscope before and after treatment, 3x to observe the efficacy according to the values of the patients' UV shallow and deep spots and brown spots. The smaller the values, the lighter the melasma.
- Statistically analyze the changes in the UV-shallow and -deep spots and brown spots before and after treatment.
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Representative Results
Case 1, a 57-year-old female with a medical history of 10 years, was selected for treatment and efficacy evaluation. The efficacy of the combination of roller microneedle and tranexamic acid solution was evaluated before treatment and after three treatment sessions (Figure 2, Figure 3, and Figure 4) and observed from different angles using a multispectral dermatoscope. A reduction of 35.91 mm2, 163.32 mm2, and 82.4 mm2 was observed in the frontal view for UV shallow spots, UV deep spots, and brown area, respectively. A reduction of 57.7 mm2, 42.68 mm2, and 48.52 mm2 was presented in the right lateral view of 45° for UV shallow spots, UV deep spots, and brown area, respectively. A reduction of 24.3 mm2, 51.39 mm2, and 47.39 mm2 was shown in the left lateral view of 45° for UV shallow spots, UV deep spots, and brown area, respectively.
Case 2, a 44-year-old female with a medical history of 2 years, also showed efficacy of the treatment after three treatment sessions (Figure 5, Figure 6, and Figure 7). A reduction of 119.4 mm2, 61.39 mm2, and 3.81 mm2 was observed in the frontal view for UV shallow spots, UV deep spots, and brown area, respectively. A reduction of 46.89 mm2, 8.11 mm2, and 34.29 mm2 was presented in the right lateral view of 45° for UV shallow spots, UV deep spots, and brown area, respectively. A reduction of 15.52 mm2, 20.47 mm2, and 28.45 mm2 was shown in the left lateral view of 45° for UV shallow spots, UV deep spots, and brown area, respectively.
After three treatments with roller microneedles combined with a tranexamic acid solution, the brown patches became lighter for both cases and the number of UV-shallow and -deep spots also decreased as well as the brown area.
Figure 1: Roller microneedles (0.22 x 0.5 mm). Please click here to view a larger version of this figure.
Figure 2: Frontal views of Case 1. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 210.58 mm2; (B)image presents UV-deep spots before treatment: 1,834.53 mm2; (C) image shows brown area before treatment: 925.47 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 174.67 mm2; (E) image presents UV-deep spots after three treatment sessions: 1,671.21 mm2; (F) image shows the brown area after three treatment sessions: 843.07 mm2. Please click here to view a larger version of this figure.
Figure 3: Right lateral view at 45° of Case 1. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 338.4 mm2; (B) image presents UV-deep spots before treatment: 479.29 mm2; (C) image shows brown area before treatment: 544.9 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 280.7 mm2; (E) image presents UV-deep spots after three treatment sessions: 436.61 mm2; (F) image shows the brown area after three treatment sessions: 496.38 mm2. Please click here to view a larger version of this figure.
Figure 4: Left lateral view at 45° of Case 1. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 142.49 mm2; (B) image presents UV-deep spots before treatment: 578.22 mm2; (C) image shows brown area before treatment: 532.19 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 118.19 mm2; (E) image presents UV-deep spots after three treatment sessions: 526.83 mm2; (F) image shows the brown area after three treatment sessions: 484.8 mm2. Please click here to view a larger version of this figure.
Figure 5: Frontal views of Case 2. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 600.28 mm2; (B) image presents UV-deep spots before treatment: 589.42 mm2; (C) image shows brown area before treatment: 42.67 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 480.88 mm2; (E) image presents UV-deep spots after three treatment sessions: 528.03 mm2; (F) image shows the brown area after three treatment sessions: 38.86 mm2. Please click here to view a larger version of this figure.
Figure 6: Right lateral view at 45° of Case 2. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 232.11 mm2; (B) image presents UV-deep spots before treatment: 90.93 mm2; (C) image shows brown area before treatment: 384.98 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 185.22 mm2; (E) image presents UV-deep spots after three treatment sessions: 82.82 mm2; (F) image shows the brown area after three treatment sessions: 350.69 mm2. Please click here to view a larger version of this figure.
Figure 7: Left lateral view at 45° of Case 2. (A-C) Before treatment and (D-F) after three treatment sessions, under the Multispectral Dermoscope. (A) Image shows UV-shallow spots before treatment: 90.94 mm2; (B) image presents UV-deep spots before treatment: 229.85 mm2; (C) image shows brown area before treatment: 319.38 mm2. (D) Image shows UV-shallow spots after three treatment sessions: 75.42 mm2; (E) image presents UV-deep spots after three treatment sessions: 209.38 mm2; (F) image shows the brown area after three treatment sessions: 290.93 mm2. Please click here to view a larger version of this figure.
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Discussion
The pathogenesis of melasma is complex, and treatment methods include systemic medication, topical depigmenting agents, chemical peels, and laser therapy. Unfortunately, no single treatment is universally effective for all patients, and satisfactory results cannot be always guaranteed6. Phototherapy shows a decreasing trend in treating melasma, and some patients experience worsening of melasma after phototherapy. This is due to an increase in individuals with sensitive skin and impaired skin barrier function in inflammatory melasma. Laser or other treatments targeting melanin may intensify the skin's inflammatory response, leading to exacerbation of melasma symptoms. Consequently, recent advancements in melasma treatment focus on safety and non-irritating methods, with a particular emphasis on restoring skin barrier function as a new target for therapy.
Advantages of roller microneedle combined with tranexamic acid
Microneedle treatment has significant advantages over other transdermal drug delivery methods, with low complication rates and the shortest dwell time7. Additionally, it can be applied to patients with skin of color (Fitzpatrick skin types IV-VI)8. The micro-injuries caused by the roller microneedle on the skin are minimal, and the tiny puncture wounds are localized, preserving surrounding normal tissue and providing a favorable foundation for skin repair. After treatment, there is little or no bleeding, minimal exudation, and superficial scab formation. The inflammatory reaction is mild, and healing occurs quickly with minimal side effects. Compared to phototherapy, which unavoidably causes thermal damage, the risk of posttreatment hyperpigmentation is reduced to some extent. This "micro-injury-repair" process stimulates collagen regeneration and enhances cellular metabolism while having minimal adverse effects. Scarring and hyperpigmentation are rare, making it a safe and effective treatment method. The roller microneedle treatment for melasma is performed once every 4 weeks, 3x over the course of treatment. After a course of treatment, maintenance treatments are conducted once every 4 weeks until the melasma fades.
Besides its anti-hemorrhagic and antifibrinolytic effects, tranexamic acid also possesses anti-inflammatory and skin-whitening properties. It was the first systemic medication studied for treating melasma. There is substantial evidence supporting the efficacy of oral tranexamic acid in treating melasma; however, it may lead to systemic side effects9. Topical application of tranexamic acid has been proven to be as effective as standard treatments for melasma (e.g., topical hydroquinone) but with fewer side effects10,11. Although the exact mechanism and biochemical pathways of tranexamic acid in treating melasma are not fully understood, its impact on reducing skin pigmentation has been well-established. It can decrease melanin production and is believed to reduce the number of blood vessels and erythema in melasma by inhibiting plasmin and basic fibroblast growth factor12,13. Additionally, tranexamic acid plays a role in the epidermal barrier14,15.
Microneedle treatment promotes fibroblast proliferation and dermal collagen reconstruction, repairing the dermal and basement membrane damage in melasma. It reduces the release of pro-melanogenic signals from the dermis, increases the turnover of epidermal melanin, and promotes the normalization of the skin structure in hyperpigmented areas16. Microneedle treatment creates microchannels in the skin, allowing tranexamic acid to be delivered into the skin. When combined with tranexamic acid, microneedle treatment improves melasma and may be superior to intradermal injections of tranexamic acid when compared to the topical application alone6. Currently, the available treatment options for melasma show suboptimal results, with incomplete pigment clearance and high recurrence rates. Saleh et al. observed the efficacy of topical tranexamic acid combined with microneedles in the treatment of melasma, and at 12 weeks, the improvement rate of the Melasma Area and Severity Index (MASI) was 62.1%17. The roller microneedle is a useful adjunctive approach for the localized treatment of melasma. For patients with challenging localized melasma, clinicians should consider microneedle treatment as an upgrade option before starting chemical peels, laser therapy, or systemic medications18.
Limitations and precautions for roller microneedle operation
During the operation of the roller microneedle, it is essential to consider the contraindications for the patient and evaluate if their skin condition is suitable for microneedle treatment. The contraindications include skin infections (bacterial, fungal, and viral infections), skin allergy (erythema, edema, exudation, and ulceration), systemic infections (such as HIV, syphilis, various hepatitis), skin diseases that may induce isomorphic reactions (such as active stage vitiligo), severe hypertension, heart disease, diabetes, and coagulation disorders, pregnancy; the roller microneedle must be used with caution during lactation and menstruation and in individuals with a tendency to form hypertrophic scars4.
Providing a comfortable environment with appropriate temperature and lighting, effective communication between the operator and the patient, alleviating patient tension, managing posttreatment adverse reactions, as well as implementing strict sun protection and infection prevention after the procedure, are crucial aspects to be taken into account. Erythema may occur immediately after treatment, and its duration depends on the treatment intensity and the patient's skin response. Most erythema will resolve on its own within 3 days after treatment. If itching is significant after treatment, a cold compress must be applied with an ice pack for 20-30 min, or a mild topical steroid cream, such as hydrocortisone butyrate cream, used for more severe cases. If symptoms of infection appear after the procedure, the causative pathogen and symptoms must be treated accordingly. Boric acid solution must be applied topically and antibiotic or antiviral ointment administered twice daily. In severe cases, oral antibiotics or antiviral drugs may be necessary.
Fungal infections are rare. Scarring is rare and usually occurs as a result of infection. Patients with existing infections should be treated using the aforementioned measures earlier to prevent scarring. For patients with existing scars, treatment options include pigment laser, intense pulsed light (IPL), fractional laser, localized injections, topical anti-scarring creams, or patches. Due to the disruption of the skin's stratum corneum during roller microneedle treatments, the skin may temporarily experience dryness, redness, itching, and increased irritability. Patients with thinner stratum corneum and sensitive skin may be more sensitive to external stimuli and may experience mild sensations of burning or discomfort. Medical repair masks and specialized repair creams can be applied to sensitive skin. If necessary, cold sprays or red and yellow light exposure may be used. It is advisable to extend the time between subsequent treatments until the skin stabilizes and the barrier function is restored. During this period, other invasive treatments that may worsen sensitivity must be avoided.
Although the risk of infection during microneedle treatment is minimal, there is still a risk if preoperative disinfection is not thorough, sterile principles are not strictly followed during the procedure, or postprocedure patient care is inadequate. With continuous improvements in microneedle materials and topical formulations of tranexamic acid, the combination of roller microneedle and topical medication is expected to yield better therapeutic outcomes for melasma.
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Disclosures
The authors have no conflicts of interest to declare.
Acknowledgments
This work was financially supported by the Key Project of Medical Research Jointly from Chongqing Health Commission and Chongqing Science and Technology Bureau (2022ZDXM037), the Key Projects of Scientific Research Fund of Traditional Chinese Medicine of Wuhan Health Commission (WZ22A03), and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0592).
Materials
| Name | Company | Catalog Number | Comments |
| 5 mL syringe | |||
| Benzalkonium bromide solution | Chongqing Traditional Chinese Medicine Hospital | H20050531 | 0.1% |
| cling film | |||
| Compound lidocaine cream | Beijing Ziguang Pharmaceutical Co., Ltd. | H20063466 | 5.0% |
| disinfectant towel | |||
| disposable curved disc | |||
| Multispectral Dermoscope | CBS Medical Skin Analysis, Wuhan, China | CBS-2022 | |
| Roller microneedle | Guangzhou Yuanxiang Biotechnology Co., Ltd | 221001 | (model: 0.22 x 0.5 mm, Figure 1) |
| Sodium chloride solution | Hubei Tiansheng Pharmaceutical Co., Ltd. | H42021838 | 0.9% |
| sterile cotton swab | |||
| sterile gauze | |||
| sterile gloves | |||
| tongue depressor | |||
| Tranexamic acid solution | Shanghai Hyundai Hasen (Shangqiu) Pharmaceutical Co., Ltd. | H20184047 | 5.0% |
| treatment vehicle |
References
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