Skin necrosis after intradermal injection of lyophilized exosome: A case report and a review of the literature.

BACKGROUND: Exosomes have gained attention for their potential in skin rejuvenation. Currently, most exosome products are available for topical administration, and the use of subdermal injection as a route of administration has not been approved. AIMS: The purpose of this case report is to describe a case of skin necrosis that occurred following an intradermal injection of lyophilized exosomes. MATERIALS AND METHODS: We hereby report a case of a middle-aged man who experienced adverse effects after receiving an intradermal injection of lyophilized exosomes. Multiple injections of an exosome product were administered to treat enlarged facial pores. Shortly after the injection, the patient felt pain and noticed several dark red bumps. Three days after injection, the lesions transformed into palpable, painful, non-blanchable purplish papules and nodules, accompanied by central, tiny crusted erosions. The residual product was injected into the upper arm using an intradermal method. Similar lesions also appeared, and a skin biopsy showed necrotic keratinocytes, leukocytoclastic vasculitis, and eccrine necrosis. RESULTS: There are few reports available regarding complications, especially those related to intradermal exosomes. These complications include multiple foreign-body granulomatous reactions at the injection sites. In our case, oral prednisolone was administered for a duration of 7 days. After the treatment, the lesions exhibited notable improvement, eventually leaving post-inflammatory hyperpigmentation. CONCLUSION: Utilizing exosomes through unapproved methods should be avoided due to the possibility of adverse reactions that could cause aesthetic issues.

Local delivery of low-dose anti-CTLA-4 to the melanoma lymphatic basin leads to systemic Treg reduction and effector T cell activation.

Preclinical studies show that locoregional CTLA-4 blockade is equally effective in inducing tumor eradication as systemic delivery, without the added risk of immune-related side effects. This efficacy is related to access of the CTLA-4 blocking antibodies to tumor-draining lymph nodes (TDLNs). Local delivery of anti-CTLA-4 after surgical removal of primary melanoma, before sentinel lymph node biopsy (SLNB), provides a unique setting to clinically assess the role of TDLN in the biological efficacy of locoregional CTLA-4 blockade. Here, we have evaluated the safety, tolerability, and immunomodulatory effects in the SLN and peripheral blood of a single dose of tremelimumab [a fully human immunoglobulin gamma-2 (IgG2) mAb directed against CTLA-4] in a dose range of 2 to 20 mg, injected intradermally at the tumor excision site 1 week before SLNB in 13 patients with early-stage melanoma (phase 1 trial; NCT04274816). Intradermal delivery was safe and well tolerated and induced activation of migratory dendritic cell (DC) subsets in the SLN. It also induced profound and durable decreases in regulatory T cell (Treg) frequencies and activation of effector T cells in both SLN and peripheral blood. Moreover, systemic T cell responses against NY-ESO-1 or MART-1 were primed or boosted (N = 7), in association with T cell activation and central memory T cell differentiation. These findings indicate that local administration of anti-CTLA-4 may offer a safe and promising adjuvant treatment strategy for patients with early-stage melanoma. Moreover, our data demonstrate a central role for TDLN in the biological efficacy of CTLA-4 blockade and support TDLN-targeted delivery methods.

Platelet-rich plasma versus carboxytherapy in the treatment of periorbital dark circles: A split-face study.

BACKGROUND: Periorbital hyperpigmentation is a recurrent problem in dermatologic clinics that affect the patients' quality of life and their psychological status. Platelet-rich plasma (PRP) may serve as a source of different growth factors which may reduce the pigmentation in this problem. Carboxytherapy is carbon dioxide infusion into human tissue for therapeutic purposes. OBJECTIVE: To evaluate and compare the clinical efficacy of PRP and carboxytherapy in the treatment of periorbital dark circles (PODC). Histopathological evaluation was also done. PATIENTS AND METHODS: Split-face study of 23 patients with PODC treated with PRP at the right side and carboxytherapy at the left side. Patients received four sessions; one session/week. Final follow-up evaluation was done 3 months after the last session by clinical and histopathological assessment. RESULTS: PRP showed significant better response (p = 0.002), shorter downtime, and tolerable side effects than caboxytherapy. Reduction in area percent of melanin after PRP injections showed 46.6% improvement, while after carboxytherapy, it showed only 14.3% improvement. CONCLUSION: The present study showed that PRP is more effective and tolerable than caboxytherapy in the treatment of PODC.

Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections - a randomized controlled trial.

BACKGROUND: Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women's impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections. METHODS: The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections. RESULTS: The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported. CONCLUSION: Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections. TRIAL REGISTRATION: The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185 .

Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.

BACKGROUND: Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. RESULTS: The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-ß receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. CONCLUSIONS: In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).

Bleomycin administered by laser-assisted drug delivery or intradermal needle-injection results in distinct biodistribution patterns in skin: in vivo investigations with mass spectrometry imaging.

Bleomycin (BLM) is being repositioned in dermato-oncology for intralesional and intra-tumoural use. Although conventionally administered by local needle injections (NIs), ablative fractional lasers (AFLs) can facilitate topical BLM delivery. Adding local electroporation (EP) can augment intracellular uptake in the target tissue. Here, we characterize and compare BLM biodistribution patterns, cutaneous pharmacokinetic profiles, and tolerability in an in vivo pig model following fractional laser-assisted topical drug delivery and intradermal NI, with and without subsequent EP. In vivo pig skin was treated with AFL and topical BLM or NI with BLM, alone or with additional EP, and followed for 1, 2 and 4 h and eventually up to 9 d. BLM biodistribution was assessed by spatiotemporal mass spectrometry imaging. Cutaneous pharmacokinetics were assessed by mass spectrometry quantification and temporal imaging. Tolerability was evaluated by local skin reactions (LSRs) and skin integrity measurements. AFL and NI resulted in distinct BLM biodistributions: AFL resulted in a horizontal belt-shaped BLM distribution along the skin surface, and NI resulted in BLM radiating from the injection site. Cutaneous pharmacokinetic analyses and temporal imaging showed a substantial reduction in BLM concentration within the first few hours following administration. LSRs were tolerable overall, and all interventions permitted almost complete recovery of skin integrity within 9 d. In conclusion, AFL and NI result in distinct cutaneous biodistribution patterns and pharmacokinetic profiles for BLM applied to in vivo skin. Evaluation of LSRs showed that both methods were similarly tolerable, and each method has potential for individualized approaches in a clinical setting.

Generation of Filler Emboli as a Mechanism for Filler-Related Blindness.

BACKGROUND: Intra-arterial injection of fillers can lead to occlusion of the ophthalmic artery or its branches supplying the retina or the optic nerve. The mechanism through which this occurs is incompletely understood. We investigated the possibility of generating microparticles after injecting commercially available fillers into a flowing system in vitro. METHODS: Three hyaluronic acid fillers and one calcium hydroxylapatite filler were injected into an artificial saline flow system mimicking arterial systolic blood pressure and corresponding to the diameter of the facial artery. All the saline at the end of the tube was collected, centrifuged, and inspected for filler particles. RESULTS: After injection into the system, all fillers immediately disintegrated into small particles that were carried downstream with the flow of the saline. The saline at the end of the tube contained collections of filler. CONCLUSION: Hyaluronic acid and hydroxylapatite fillers break up into small particles immediately after injection into a flowing system, generating emboli rather than a column of filler. The results of this study lead us to hypothesize another potential mechanism leading to filler-related blindness.

Fractional CO2 Laser for Transcutaneous Drug Delivery of Onabotulinum Toxin in Palmar Hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis is a common disorder of excessive sweating due to over-stimulation of cholinergic receptors on eccrine glands. OBJECTIVE: To compare the efficacy of laser-assisted drug delivery of onabotulinum toxin A (BoNTA) and intradermal BoNTA injections in the management of palmar hyperhidrosis. PATIENTS AND METHODS: This intrapatient comparative study was conducted on 30 adult patients with idiopathic palmar hyperhidrosis. The palms of the patients were divided into 2 groups. Group 1 was treated with intradermal injections of 50 units of BoNTA, whereas Group 2 was subjected to laser-assisted transcutaneous BoNTA delivery using fractional CO2 laser at different doses (25, 50, and 75 units). Each treatment modality was evaluated using the iodine starch test, hyperhidrosis disease severity scale, and gravimetric scoring. RESULTS: Delivery of 75 units of BoNTA to the dermis on the right-sided palms assisted by fractional CO2 laser was clinically equivalent to 50 units of injection on the left side. Pain intensity was significantly higher on the injected side than on the other side. CONCLUSION: Laser-assisted drug delivery of botulinum toxin can be considered an effective and safe alternative for treatment of palmar hyperhidrosis with minimal side effects and complications.

Anatomic Danger Zones of the Head and Neck.

BACKGROUND: Dermatologic procedures require a detailed understanding of surface anatomy to avoid complications. The head and neck region has prominent danger zones including nerves and vasculature that may be at risk during cutaneous surgery. A thorough understanding of these danger zones can help avoid complications that may lead to functional or cosmetic impairment. METHODS: The anatomic literature regarding the course of high-risk structures of the head and neck was reviewed. Structures deemed at risk during dermatologic procedures were included in the analysis. The final analysis focused on branches of the facial nerve, parotid duct, spinal accessory nerve, trigeminal nerve, and the lacrimal system. Anatomical information was compiled regarding each high-risk structure to develop a "danger zone" at which each respective structure is at risk. RESULTS: The danger zone for each structure was compiled based on the review of the literature and depicted in the figures. CONCLUSION: With careful attention to anatomy and the meticulous surgical technique, there is great potential for reduction in surgical injury to danger zones of the head and neck.

Granulomas and nongranulomatous nodules after filler injection: Different complications require different treatments.

Dermal fillers are widely used for facial rejuvenation and reconstruction and present fewer risks than surgical approaches. Nevertheless, several complications may occur, including nodule formation. A nodule is a clinical sign corresponding to different etiologies, such as overcorrection, infection, allergic reaction, or granuloma. However, their treatment represents a diagnostic challenge. We present a retrospective review of 26 consecutive patients who underwent a biopsy for facial nodule formation more than 3 months after filler injections, to determine the diagnosis of the nodule and type of filler used. All patients were women (mean age, 57.8 years). Some patients suffered from different localizations: lip, 14 cases; nasolabial folds, 6; cheeks, 5; infraorbital region, 5; the glabella, 2; the temporal region, 1; and chin, 1 case. Only 5 (19.2%) patients knew the type of filler used, and in another 4 cases, the injector was able to provide some information. In 65.4% of cases, the filler type was unknown. Histopathological analysis revealed a "granulomatous" nodule in 30 sites and a "non-granulomatous" nodule in 4 cases. Concerning the type of filler, 5 different histopathological patterns were found. Our results demonstrate that a clinical history and histopathological analysis whether to confirm or not to confirm the diagnosis of granuloma and to identify the type of filler are essential tools to achieve an accurate diagnosis of the problem-oriented treatment of nodules after dermal filler injections. We propose an algorithm for the management of nodules after filler injection.

Tranexamic Acid for Melasma Treatment: A Split-Face Study.

BACKGROUND: Melasma is an acquired hyperpigmented skin disorder. Tranexamic acid (TXA) prevents ultraviolet radiation induced pigmentation in melasma through interfering with the plasminogen-plasmin pathway. OBJECTIVE: This study was conducted to evaluate the therapeutic effect and safety of TXA by intradermal injection versus TXA with microneedling for melasma treatment. METHODS: Fifty-six female patients with bilateral symmetrical melasma were recruited in a split-face study. All patients received an intradermal injection of TXA on one side of the face, and the other side received TXA with microneedling for 6 sessions at 2 weeks intervals. Clinical efficacy was assessed using a modified Melasma Area Severity Index (mMASI) score at the baseline and after treatment. Global photographs underwent blinded review by 2 dermatologists. Patient self-assessment and satisfaction were recorded. RESULTS: After the treatment, the mMASI score was significantly reduced compared with the baseline in both treated sides (p < .001). No significant difference between both treated sides (p > .05). Patient satisfaction was higher in the microneedling-treated side than the intradermal-injected side (p < .001). No significant adverse effects were observed in both treated sides. CONCLUSION: Intradermal injection and microneedling of TXA could be safe and effective in melasma treatment. Microneedling of TXA was significantly more satisfying to the patients.

A grading system for local skin reactions developed for clinical trials of an intradermal and transcutaneous ETEC vaccine.

BACKGROUND: Trials assessing the safety of novel vaccine candidates are essential in the evaluation and development of candidate vaccines. Immunogenicity and dose-sparing features of vaccination approaches which target skin and associated tissues have garnered increased interest; for enteric vaccines, cutaneous vaccination has been of particular interest. Cutaneous vaccine site reactions are among the most common and visible vaccine related adverse events (AEs) when skin routes are used. Regulatory guidelines governing classification of severity focus on functional impact but are insufficient to characterize a spectrum of skin reaction and allow for comparisons of routes, doses and products with similar local cutaneous AEs. OBJECTIVES: Our group developed a grading scale to evaluate and compare cutaneous vaccine site reactions ahead of early-phase clinical trials of intradermal (ID) and transcutaneous immunization (TCI) with enterotoxigenic E.coli (ETEC) vaccine candidates (adhesin-based vaccine co-administered with LTR192G). We reviewed existing methods for characterizing the appearance and severity of local vaccine site reactions following TCI and ID vaccination and devised a standardized vaccine site appearance grading scale (VSAGS) for use in the clinical development of novel ETEC vaccine candidates which focused on pathophysiologic manifestation of skin findings. RESULTS: Available data from published reports revealed erythematous papules and pruritus were the most common local AEs associated with TCI. Frequency of reactions varied notably across studies as did TCI vaccination methodologies and products. ID vaccination commonly results in erythema and induration at the vaccine site as well as pigmentation changes. There was no published methodology to characterize the spectrum of dermatologic findings. CONCLUSION: ID and TCI vaccination are associated with a largely predictable range of cutaneous AEs. A grading scale focused on the appearance of cutaneous changes was useful in comparing cutaneous AEs. A standardized grading scale will facilitate documentation and comparison of cutaneous AEs.

Preinjection aspiration for injectable fillers in aesthetic dermatology: Trust or bust?

In recent years, the utility of preinjection aspiration for injectable fillers as a safety checkpoint has been debated. It is a clinical technique that has become controversial in both the literature and at national aesthetic conferences. Many consensus papers and anecdotal reports have been divided on how helpful preinjection aspiration is in reducing adverse events and subsequently increasing patient safety. Here, we summarize the prominent studies in the literature and offer an evaluation and insights.

New Classification Schemata of Hypersensitivity Adverse Effects After Hyaluronic Acid Injections: Pathophysiology, Treatment Algorithm, and Prevention.

BACKGROUND: Side effects during hyaluronic acid (HA) injection are considered mild and reversible; however, an alarming trend of increased hypersensitivity reactions has recently been reported. OBJECTIVE: The goal of this article is to review the hypersensitivity reactions reported in the literature and, in combination with the authors' experience, to create a classification system to sort the timing and clinical manifestations of these reactions, as well as a treatment schema to manage their clinical course. METHODS: A literature search using PubMed, Ovid MEDLINE, and Embase databases was performed with no date restrictions. Search terms included "hyaluronic acid and hypersensitivity" and "hyaluronic acid and nodules." Data analyzed included study type, number of subjects, HA filler type, injection location, adverse reaction, timing, treatment, and outcomes. RESULTS: Thirty-six studies were identified, documenting hypersensitivity reactions to HA treatment. Twelve cases described events occurring within a week, 6 within a month, and 31 after a month of treatment. Combined with the authors' experience, a new classification system and management of hypersensitivity reactions to HA fillers is proposed of early (up to a week), intermediate (a week to a month), and late (over a month) hypersensitivity reactions. CONCLUSION: The classification system proposed provides objective measurements and management options that can be helpful for physicians to navigate these hypersensitivity reactions and design treatment protocols that provide the best clinical outcomes for their patients.

Study of efficacy of microneedling and mesoneedling in the treatment of epidermal melasma: A pilot trial.

BACKGROUND: Melasma is a difficult to treat pigmentation disorder. However, some successes have been attained by microneedling. The aim of the present study was to evaluate the efficacy of microneedling using meso-depigmentation solution (mesoneedling) in comparison with standard microneedling, over a 4-month treatment period. METHODS: As a part of this pilot study, 20 patients received microneedling on one side and mesoneedling on another side of their face. Treatment was repeated on a monthly basis for 4 months. Treatment efficacy was defined through Dermacatch® colorimetry, modified Melasma Area and Severity (mMASI) score determination, Investigator's Global Assessment (IGA), and patient questionnaires, whereby all assessments were conducted at the baseline, as well after 2 and 4 months of treatment. RESULTS: Before treatments, mean difference between pigmented and normal skin calculated by Dermacatch® was 43.7 ± 20.12 and 44.6 ± 20.72 in microneedling sides and mesoneedling sides, respectively. After two and four sessions, these values declined to 34.5 ± 16.26 and 28.05 ± 13.79 on the side subjected to microneedling, while 29.75 ± 15.07 and 20.45 ± 10.58 were measured on the mesoneedling side. Statistically significant differences have been observed between microneedling and mesoneedling treatments at both time points (P = .0001, P = .0001). The mMASI scores obtained upon treatment completion were significantly lower on both the microneedling and the mesoneedling side. The IGA and patients' self-assessment scores further confirmed that both treatments were effective in treating melasma, without producing any notable side-effects or complications. CONCLUSION: In sum, both microneedling and mesoneedling are effective in decreasing melanin content in the epidermal melasma lesions.

A prospective comparison between skin cooling and skin vibration in reducing the pain of local anesthetic infiltration.

BACKGROUND: Growing evidence supports skin cooling (cryoanalgesia) or skin vibration (vibroanalgesia) as potential techniques for pain alleviation. AIMS: To compare the effect of skin vibration using the Buzzy® vibration device with that of skin cooling for 2 minutes, as methods to reduce the pain of 1% lidocaine-epinephrine infiltration. METHODS & MATERIALS: Sixty healthy volunteers were recruited for this prospective study. Each subject received an intradermal injection of the anesthetic solution after application of the Buzzy® vibration device in one arm and another injection after ice application in the other arm. After each injection, the subjects rated pain of infiltration on a 100-mm visual analog scale. Pain scores were compared using a paired t test. RESULTS: Twenty-seven of sixty subjects (45%) reported that the 1% lidocaine-epinephrine infiltration after skin cooling was more painful than after skin vibration. Eleven subjects (18.3%) gave the same pain score for both techniques. The mean pain score ± SD was 30 ± 23.14 after skin cooling and 25.5 ± 24.1 after skin vibration. The difference between mean values was not statistically significant. CONCLUSION: Skin vibration may be more effective than skin cooling in alleviating the pain caused by local anesthetic infiltration, although the difference was not statistically significant.

Ocular complications of soft tissue filler injections: A review of literature.

BACKGROUND: Soft tissue filler is commonly used for facial contouring. However, incorrect use can lead to severe ocular complications. Even though filler injections are quite different from fat grafts, they are considered similar procedures. However, to date, there are no proven preventive measures or treatments for blindness secondary to soft tissue filler injections. OBJECTIVES: This literature review aimed to investigate visual compromise secondary to soft tissue filler injection and discuss the related vascular anatomy, pathophysiology, and prevention of ocular complications of soft tissue filler injections. METHODS: A literature search until July 2018 was performed for reports on visual compromise after filler injections. We evaluated the previous literature and eliminated cases using fat grafts and unknown fillers. RESULTS: A total of 50 reports of filler-induced visual compromise were identified. Analysis of these cases showed that the procedure with greatest risk was nasal augmentation, followed by glabellar wrinkle treatment. Within the last 3 years searched, 35% of reported cases involved treatment of the nose. There were no reports of blindness from injections into the temple or chin and relatively few case reports involving forehead injections. CONCLUSION: The most common injection site associated with blindness in a previous report was the glabella; however, the most common site currently associated with blindness due to filler injections was the nose. Extreme caution is necessary when performing nasal augmentation or glabellar wrinkle correction using soft tissue fillers to avoid the branches of the internal carotid artery.

Platelet-rich plasma treatment for melasma: A pilot study.

BACKGROUND: Melasma treatments have varying success and are associated with some complications. AIMS: To assess the effectiveness of platelet-rich plasma (PRP) treatment for melasma. METHODS: Ten female patients with bilateral mixed-type melasma were enrolled in our randomized, split-face, single-blinded prospective trial. Over 4 treatment sessions that each took place every 2 weeks, PRP was injected intradermally on one side of the face (PRP condition) and normal saline on the other (control condition). PRP was prepared by using the YCELLBIO Kit® . Outcomes were evaluated with the modified Melasma Area and Severity Index (mMASI), Mexameter® , and Antera® 3D. Patient satisfaction was also assessed at baseline, at 2, 4, and 6 weeks, and 1 month after treatment completion. RESULTS: mMASI score and Antera® 3D-assessed melanin levels show significant improvement in the PRP condition than control condition between baseline and week 6, while patient satisfaction significantly increased over time. However, Mexameter® -assessed erythema and melanin indices did not significantly differ between the control and PRP conditions, though there was a trend toward reduced pigmentation in the latter. Finally, side effects of treatment were mild and resolved spontaneously within a few days. CONCLUSION: This is the first randomized, placebo-controlled trial study using PRP for treatment of melasma. PRP injection significantly improved melasma within 6 weeks of treatment in terms of mMASI scores, patient satisfaction, and Antera® -assessed melanin levels. Hence, intradermal PRP injection could be used as an alternative or adjuvant therapy for melasma. However, additional trials are needed for more rigorous evaluation of its long-term efficacy and safety.