A Novel Regimen of Transdermal Botulinum Toxin Delivery Using Fractional Microneedling Radiofrequency for Treatment of Erythema in Rosacea

Park, Jin Seo; Lee, So Yeon; Kim, Jin Cheol; Park, Chun Wook; Kim, Hye One; Chung, Bo Young

doi:https://doi.org/10.1155/2023/8838206

Dermatologic Therapy

On this page

Abstract Introduction Materials and Methods Results Discussion Conclusions Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2023 | Article ID 8838206 | https://doi.org/10.1155/2023/8838206

A Novel Regimen of Transdermal Botulinum Toxin Delivery Using Fractional Microneedling Radiofrequency for Treatment of Erythema in Rosacea

Jin Seo Park,¹So Yeon Lee,¹Jin Cheol Kim,¹Chun Wook Park,¹Hye One Kim,¹and Bo Young Chung¹

Academic Editor: Imran Majid

Received11 Mar 2023

Revised08 May 2023

Accepted10 Jul 2023

Published19 Jul 2023

Abstract

Facial erythema is a representative symptom of rosacea patients that greatly impairs quality of life. Recently, the therapeutic effects of intradermal injection of botulinum toxin type-A on erythema have been investigated. Fractional microneedling radiofrequency has been reported to be effective in dermal remodeling and anti-inflammation. To obtain enhanced therapeutic effects with a less painful and easier approach, a treatment regimen using transdermal botulinum toxin delivery with fractional microneedling radiofrequency was developed. We aimed at investigating the efficacy and safety of transdermal botulinum toxin delivery with fractional microneedling radiofrequency in treating the erythema of rosacea. This was a retrospective review of 20 patients with facial erythema associated with rosacea. All patients underwent two sessions of treatment at 4-week intervals. Standardized photographs were taken, and the clinicians' erythema assessment (CEA), erythema index (EI) measured through a spectrophotometer, investigator’s global assessment (IGA), and subjective satisfaction and side effects were evaluated at the baseline and 4, 8, and 12 weeks after the baseline. Compared to the baseline, CEA levels significantly decreased after 8 weeks () and 12 weeks (). As an objective measure, EI was observed to decrease significantly at 4 weeks () and 8 weeks after the baseline () compared with the baseline. Ninety-five percent of patients were either very satisfied or satisfied with the treatment. None of the patients experienced remarkable side effects. A novel treatment regimen involving transdermal botulinum toxin delivery and fractional microneedling radiofrequency may be an effective and safe option for reducing the facial erythema of rosacea.

1. Introduction

Rosacea is a chronic inflammatory skin condition characterized by persistent central facial erythema. It is relatively common, with a prevalence of 1–22% [1]. As rosacea adversely affects appearance and induces disturbing symptoms such as flushing, it can have a detrimental influence on the psychosocial well-being of patients. Common treatment options include oral antibiotics, topical medications such as metronidazole, and light-based therapy such as laser or intense pulsed light [2]. However, the response to treatment is often incomplete, and relapses are common, underscoring the need for new and efficient treatment options.

In recent years, intradermal botulinum toxin A (BTA) has been studied as a treatment for facial erythema, and many studies have demonstrated favorable outcomes [3–9]. Fractional microneedling radiofrequency (FMR) is an emerging treatment device used across various dermatological areas. In addition, FMR therapy has been reported to alleviate erythema related to rosacea [10, 11] and postinflammatory erythema in patients with acne [12].

In this study, we adopted FMR to improve drug delivery while showing its synergistic effect with BTA on erythema improvement. We aimed at investigating the therapeutic effect of alleviating resistant erythema related to rosacea and the safety of the transdermal delivery of BTA with FMR.

2. Materials and Methods

2.1. Patients

We performed a retrospective chart review with 20 patients treated at a single center between January 2021 and April 2022. The patients presented with central facial erythema related to rosacea. Furthermore, conventional treatment modalities for rosacea had previously failed in these patients. Patients had not been previously treated for rosacea for at least 6 months. Exclusion criteria to the study treatment were as follows: (1) patients <18 years of age; (2) infection of the target area; (3) known hypersensitivity to any of the ingredients of BTA or local anesthetic cream; (4) pregnancy or lactation; and (5) history of facial keloid scarring. All the patients were informed about the procedure, including the mechanism of action, recovery, and potential side effects prior to the treatment, and informed consent was obtained.

2.2. Botulinum Toxin Preparation

A 50-unit vial of letibotulinum toxin A (Botulax; Hugel Inc., Chuncheon, Korea) was diluted to 2 units/0.1 mL with 2.5 mL of 0.9% sodium chloride. The solution was prepared in 15 units for each cheek and 3 units each for the nose, glabella, and supraeyebrow area.

2.3. Treatment Device

An FMR device (Potenza, Jeisys Medical Inc., Seoul, Korea) was used for the treatment. The device was coupled with the CP21 pumping tip designed for drug delivery. The tip consists of 21 microneedle electrodes with a diameter of 350 μm. All microneedles are insulated, except for the lower 0.3 mm, and the length can be adjusted from 0.5 to 2.5 mm, depending on the anatomical site. During the procedure, 6 W of monopolar radiofrequency energy was delivered locally from the microneedle with each shot. The FMR device delivered the drug through the pumping technique [13]. First, the needles penetrated the dermis, and the chamber entered a vacuum state. Next, the radiofrequency energy was delivered to the dermis, and the needles were ejected. The vacuum state was lost, and the resulting change in airflow pressure enabled the drug to penetrate the dermal layer.

2.4. Protocol

Patients underwent the treatment in two sessions: visit 1 (baseline) and visit 2 (4 weeks after the baseline). Patients were instructed to return to the clinic for two additional posttreatment evaluations at 8 weeks (visit 3) and 12 weeks after the baseline (visit 4). All patients received the same treatment regimen from a single dermatologist.

Topical anesthetic cream (Encain®; a mixture of lidocaine 2.5% and prilocaine 2.5%; Kolma Korea Co., Seoul, Korea) was applied to the face 30 min prior to the treatment. The BTA solution was applied to erythematous lesions on the face by spraying with a 30-gauge insulin syringe immediately before operation with the FMR device. Then, drug delivery to the dermis was performed using the FMR device coupled with the CP21 pumping tip. The FMR device was used with the following parameters: pumping mode, 1-MHz frequency; 1.0–1.5 mm microneedle penetration depth; five to eight levels; and two to three passes. The area that was bleeding was wiped with saline-soaked gauze after the procedure. All participants were instructed to avoid potential triggering factors of rosacea such as the consumption of spicy or hot foods, excessive alcohol intake, and prolonged sun exposure during and after the treatment period. In addition, participants were advised to apply sunscreen regularly.

2.5. Clinical Assessment

A nontreating investigator evaluated the patients’ facial erythema using the erythema index (EI), the clinician erythema assessment (CEA), and the investigator’s global assessment (IGA). Images were obtained at each visit using the standardized photographic system Janus-I (PIE Co., Ltd., Suwon, Korea), which employs the digital camera Canon EOS 100 D (Canon Inc., Tokyo, Japan) to capture the entire face.

The EI was measured in the same cheek area at each visit using a spectrophotometer (Cortex Technology, Hadsund, Denmark). The photodetector was used to compute the index by measuring the absorbed and reflected light at a wavelength of 655 nm. The probe was applied to the skin surface in a room with constant temperature (20–24°C) and humidity (28–38%).

CEA is a standardized grading system used to assess erythema severity [14]. After the follow-up period, the investigator was shown the patients’ photographs taken at each visit and was asked to assess the severity (0 = absent, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe) while being blinded to the chronological order in which the photographs were taken.

IGA was used to evaluate the overall efficacy of the treatment. The investigator was asked to compare the photographs of visits 2 to 4 with that of visit 1 and evaluate the treatment efficacy (0 = no improvement, 1 = 0–10%, 2 = 11–20%, 3 = 21–30%, 4 = 31–40%, 5 = 41–50%, and 6 = 51–100%).

Patient satisfaction regarding improvements in erythema and associated symptoms (1 = not satisfied, 2 = less satisfied, 3 = quite satisfied, 4 = satisfied, and 5 = very satisfied) was also assessed at visit 3. The following side effects were assessed in all patients: pain, erythema, edema, muscle weakness, musculoskeletal pain, dry mouth, fatigue, headache, or eye disorders.

2.6. Statistical Analyses

To validate the importance of the difference among CEA levels at each visit, one-way repeated measures analysis of variance was performed. When analyzing the difference in CEA values between visits 1 and 4, we excluded missing data. To evaluate the treatment effect on EI, the difference between the EI values of visits 1 to 3 was analyzed through a paired t test. Statistical significance was set at . All statistical analyses were performed using IBM SPSS statistics (version 27.0; IBM Corporation, Armonk, NY, USA).

3. Results

3.1. Baseline Characteristics

Of the 20 patients, 13 were women and 7 were men, with an average age of 36.7 ± 9.94 years (range, 21–58). Eleven had Fitzpatrick skin type III, and nine had type IV. The patients were classified into four types of rosacea according to the National Rosacea Society’s standard classification system. [15]. The most common type was erythematotelangiectatic rosacea, with 13 patients (65%) being thus diagnosed; the remaining 7 patients (35%) showed the features of erythematotelangiectatic and papulopustular rosacea. No patients were diagnosed with phymatous rosacea or ocular rosacea (Table 1).

3.2. CEA

The mean CEA scores at visits 1, 2, and 3 were 2.8 ± 0.75, 2.7 ± 0.64, and 2.1 ± 0.89, respectively (Table 2). At the baseline, none of the patients had CEA levels of 0 or 1. Instead, eight (40%), eight (40%), and four (20%) patients had CEA scores of 2, 3, and 4, respectively. At visit 2, 1 patient achieved a CEA score of 1 (5%), whereas 5 (25%), 13 (65%), and 1 (5%) patient (s) achieved CEA scores of 2, 3, and 4, respectively. At visit 3, 5 (25%), 10 (50%), 3 (15%), and 2 (10%) patients had CEA scores of 1, 2, 3, and 4, respectively. At visit 4, 14 patients returned to the clinic, with 5 (35.71%), 6 (42.86%), and 3 (21.43%) patients achieving the CEA scores of 1, 2, and 3, respectively.

CEA levels were significantly more improved at visit 3 than at the baseline (). Furthermore, the average CEA level was significantly more reduced at visit 3 than at visit 2 (; Figure 1). At visit 4, CEA was significantly more improved than that at visits 1 () and 2 () but showed no significant difference compared to CEA at visit 3 ().

Representative facial photographs of the patients demonstrating improvements at each visit are shown in Figure 2.

Figure 2

Representative patients’ clinical photographs. Photographs were taken at visits 1 (a), 2 (b), 3 (c), and 4 (d). Case 1: A 21-year-old woman with erythema on the cheeks, nose, and supraeyebrow area. Her baseline clinician’s erythema assessment (CEA) score was 4, which decreased to 2 at visits 2–4. Case 2: A 42-year-old woman with erythema on the cheeks, nose, and supraeyebrow area. Her initial CEA score was 3, remained the same at visit 2, and decreased to 2 at visits 3 and 4. Case 3: A 37-year-old woman with erythema on the cheeks, glabella, and supraeyebrow area. Her baseline CEA score was 4, which decreased to 3 at visit 2, 2 at visit 3, and 1 at visit 4.

3.3. EI

The mean EI measurements at visits 1, 2, and 3 were 18.95 ± 5.19, 16.90 ± 4.99, and 16.60 ± 6.24, respectively. At visit 4, six patients had their EI values measured, and the mean EI was 16.00 ± 2.88. Compared with that at the baseline, the mean EI at visits 2 () and 3 () showed a statistically significant decrease (Figure 3).

3.4. IGA

At visit 2, the mean IGA score was 4.00 ± 3.00, indicating a 31–40% improvement. At visit 3, all patients showed improvements, with a mean IGA score of 4.90 ± 2.50, and most patients showed an improvement of ≥51%. At visit 4, 14 patients visited the clinic, and their mean IGA score was 4.21 ± 1.78, indicating that the therapeutic effect persisted even 8 weeks after the last treatment (Table 3).

3.5. Patient Satisfaction

At visit 3, the mean score was 4.3 ± 0.56. Seven patients (35%) had a score of 5, twelve (60%) had a score of 4, one (5%) had a score of 3, and none had scores of 1 or 2.

Eleven patients reported experiencing subjective symptoms such as a heating or burning sensation, itching, and stinging at the baseline, whereas the remaining nine did not report any symptoms. Moreover, all patients reporting subjective symptoms at the baseline experienced improvements.

3.6. Adverse Events

All patients reported temporary erythema and edema immediately after the treatment. However, these side effects resolved within 1-2 days. The patients reported minimal pain. None of the patients experienced immediate side effects, such as allergic reactions. No side effects were serious enough to discontinue treatment. None of the patients reported muscle weakness, dry mouth, fatigue, headaches, eye disorders, or musculoskeletal pain.

4. Discussion

Erythema is a key symptom of rosacea, and a recent consensus has designated fixed centrofacial erythema as the sole diagnostic criterion [16]. The visible manifestation of rosacea can greatly impact patients and more so than physicians anticipate. Patients often experience embarrassment, social anxiety, depression, and decreased quality of life (QoL) [17]. Among the signs and symptoms, erythema is recognized as substantially reducing QoL [18]. In addition, patient assessment of the treatment, which is based on the patient’s perception, can be lower than the physician’s assessment. This highlights the challenges in treating rosacea and the need for more effective treatments.

A rosacea classification system of four presentations called subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (granulomatous) was established in 2002, but its limitations were recognized as it did not accurately represent the presentation of patients. To address this, the ROSCO panel proposed a new classification system in 2017 that is based on patient features and encompasses the diversity of clinical presentations [16, 19, 20]. This new system includes persistent centrofacial erythema with potential trigger factors as a diagnostic feature. This updated system allows for accurate characterization of individual patients and can optimize outcomes by highlighting the most bothersome features for treatment. Persistent erythema was the main symptom that caused distress to the patients included in our study. Considering the recent updated global perspective on rosacea diagnosis and classification based on a phenotype approach, our study was focused on erythema present in any of the four subtypes of rosacea. Even in patients with papulopustular rosacea, persistent erythema was the primary symptom at the time of treatment and inflammatory papules and pustules were mainly present in small numbers in areas of erythema. Therefore, we applied the same treatment approach to areas of erythema that exhibited inflammatory papules or pustules.

Recent molecular and morphological studies have revealed that neurovascular and neuroimmune aspects play a central role in the pathophysiology of rosacea [21]. Immunohistochemistry and gene array analysis revealed that patients’ neuropeptide-encoding genes, such as vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide, were upregulated [22]. Moreover, the levels of mast cells, which are a potent contributor to the release of inflammatory and vasoactive mediators, are reportedly elevated in patients with rosacea [21]. In addition, dysesthesia, such as burning, pain, or itching, suggests the involvement of neurogenic inflammation in rosacea.

BTA inhibits the exocytosis of preformed vesicles in cholinergic nerves by cleaving the synaptosomal-associated protein 25 kDa at nerve terminals and reducing the secretion of acetylcholine [23]. Therefore, it can reduce erythema and flushing by inhibiting the cutaneous cholinergic vasodilatory system. In addition, BTA is known to modulate the secretion of inflammatory neuropeptides, such as VIP, substance P, and calcitonin gene-related peptide, and inhibit the expression of transient receptor potential vanilloid 1, all of which contribute to vasodilation and neurogenic inflammation [23–26]. Therefore, BTA not only alleviates erythema by reducing the levels of these mediators but also contributes to the reduction of inflammation and pain. Moreover, murine studies have demonstrated that BTA substantially decreases mast cell degranulation [27]. As a result of these functions, BTA helps improve erythema in rosacea.

To the best of our knowledge, this study demonstrated for the first time that the new treatment approach using transdermal delivery of BTA using FMR is safe and effective for improving erythema in patients with rosacea. Our treatment regimen was hypothesized to achieve the following effects: mechanical efficacy via needle penetration, radiofrequency energy, and drug response. According to the physician’s evaluation, the CEA levels significantly improved at the third visit, which took place 4 weeks after completion of both treatment sessions. The EI also showed a significant decline at both the second and third visits. Moreover, physician-assessed CEA and IGA indicated that the therapeutic impact was sustained at 8 weeks after the last treatment. Subjective symptoms such as flushing, burning, itching, and stinging sensations also showed overall improvements. The patients were highly satisfied with their treatment and tolerated it well, considering its safety profile and resulting adverse events. In addition, the level of pain during the procedure was reportedly minimal.

Favorable clinical results of BTA have been reported for the treatment of facial erythema and flushing [4, 8, 28] and specifically rosacea [5, 6, 29, 30]. Previous trials of BTA for rosacea have not reported any important adverse effects. However, in the real-world setting, patients often experience pain during the procedure and are concerned about direct dermal injections. Our study employed FMR and the pumping technique to facilitate drug delivery while minimizing discomfort during the procedure. Therefore, we attempted a new treatment approach for the transdermal delivery of BTA by using FMR in this study and demonstrated impressive treatment outcomes. The procedure was minimally painful, and no concerning side effects were reported.

FMR is primarily employed as a treatment option for acne scars, enlarged pores, and wrinkles [31]. Dermal structural remodeling, including neocollagenosis and neoelastogenesis, is promoted by delivering radiofrequency energy to the dermis using microneedles. In addition, researchers in a few studies have used FMR to treat rosacea. In one clinical trial, a modest improvement in rosacea was achieved with FMR [10]. Erythema, flushing, and subjective symptoms were reduced, and the effect was maintained until 2 months after the last treatment. The mechanism through which FMR affects rosacea remains unclear. Reduction of sebaceous gland activity through dermal structure remodeling and thermal effects, as well as anti-inflammatory and antiangiogenesis effects, suppression of the overactivated innate immune system, and decreased mast cell levels, likely contribute [12]. After two sessions of FMR treatment, skin biopsy samples from individuals with rosacea have shown a significant reduction in the levels of mast cells and markers such as the vascular endothelial growth factor (VEGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), interleukin-8, interleukin-37, toll-like receptor-2 (TLR-2), and transient receptor potential vanilloid (TRPV)-2, -3, and -4 [10], which are known to contribute to development of rosacea [32].

The limitations of this study include the small sample size, short follow-up period, and absence of a control group. The effects in an RF alone group and a group in which RF and BT are combined need to be compared relative to a control group. This study lacks the long-term follow-up of patients necessary to assess the duration of the improvement and the possible occurrence of relapses. Furthermore, future studies must determine the specific details of the treatment protocol, such as the concentration of BTA, the parameters of FMR treatment, and the number of treatment sessions, to achieve improved treatment outcomes.

5. Conclusions

The novel therapeutic regimen of transdermal delivery of BTA using FMR may be an effective and safe strategy for managing erythema in rosacea.

Data Availability

The datasets analyzed during the current study are only available from the corresponding author upon reasonable request.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Acknowledgments

This research was funded by the National Research Foundation of Korea (NRF-2021R1F1A1059510), Hallym University Research Fund, and Hallym University Medical Center Research Fund.

References

J. Tan and M. Berg, “Rosacea: current state of epidemiology,” Journal of the American Academy of Dermatology, vol. 69, no. 6, pp. S27–S35, 2013.
View at: Publisher Site | Google Scholar
E. J. van Zuuren, S. F. Kramer, B. R. Carter, M. A. Graber, and Z. Fedorowicz, “Effective and evidence-based management strategies for rosacea: summary of a Cochrane systematic review,” British Journal of Dermatology, vol. 165, no. 4, pp. 760–781, 2011.
View at: Publisher Site | Google Scholar
M. Yuraitis and C. I. Jacob, “Botulinum toxin for the treatment of facial flushing,” Dermatologic Surgery, vol. 30, no. 1, pp. 102–104, 2004.
View at: Publisher Site | Google Scholar
M. E. Odo, L. M. Odo, R. V. Farias et al., “Botulinum toxin for the treatment of menopausal hot flushes: a pilot study,” Dermatologic Surgery, vol. 37, no. 11, pp. 1579–1583, 2011.
View at: Publisher Site | Google Scholar
S. H. Dayan, R. N. Pritzker, and J. P. Arkins, “A new treatment regimen for rosacea: onabotulinumtoxinA,” Journal of Drugs in Dermatology, vol. 11, no. 12, pp. e76–e79, 2012.
View at: Google Scholar
K. Y. Park, M. Y. Hyun, S. Y. Jeong, B. J. Kim, M. N. Kim, and C. K. Hong, “Botulinum toxin for the treatment of refractory erythema and flushing of rosacea,” Dermatology, vol. 230, no. 4, pp. 299–301, 2015.
View at: Publisher Site | Google Scholar
B. S. Bloom, L. Payongayong, A. Mourin, and D. J. Goldberg, “Impact of intradermal abobotulinumtoxinA on facial erythema of rosacea,” Dermatologic Surgery, vol. 41, no. 1, pp. S9–S16, 2015.
View at: Publisher Site | Google Scholar
G. Eshghi, L. Khezrian, and P. Alirezaei, “Botulinum toxin A in treatment of facial flushing,” Acta Medica Iranica, vol. 54, no. 7, pp. 454–457, 2016.
View at: Google Scholar
O. Friedman, A. Koren, R. Niv, J. N. Mehrabi, and O. Artzi, “The toxic edge-A novel treatment for refractory erythema and flushing of rosacea,” Lasers in Surgery and Medicine, vol. 51, no. 4, pp. 325–331, 2019.
View at: Publisher Site | Google Scholar
S. Y. Park, H. H. Kwon, J. Y. Yoon, S. Min, and D. H. Suh, “Clinical and histologic effects of fractional microneedling radiofrequency treatment on rosacea,” Dermatologic Surgery, vol. 42, no. 12, pp. 1362–1369, 2016.
View at: Publisher Site | Google Scholar
H. H. Kwon, J. Y. Jung, W. Y. Lee, Y. Bae, and G. H. Park, “Combined treatment of recalcitrant papulopustular rosacea involving pulsed dye laser and fractional microneedling radiofrequency with low-dose isotretinoin,” Journal of Cosmetic Dermatology, vol. 19, no. 1, pp. 105–111, 2020.
View at: Publisher Site | Google Scholar
S. Min, S. Y. Park, J. Y. Yoon, H. H. Kwon, and D. H. Suh, “Fractional microneedling radiofrequency treatment for acne-related post-inflammatory erythema,” Acta Dermato-Venereologica, vol. 96, no. 1, pp. 87–91, 2016.
View at: Publisher Site | Google Scholar
J. H. Hyeong, J. W. Jung, S. B. Seo, H. S. Kim, and K. H. Kim, “Intradermal injection of poly-d, l-lactic acid using microneedle fractional radiofrequency for acne scars: an open-label prospective trial,” Dermatologic Surgery, vol. 48, no. 12, pp. 1306–1311, 2022.
View at: Publisher Site | Google Scholar
J. Tan, H. Liu, J. J. Leyden, and M. J. Leoni, “Reliability of clinician erythema assessment grading scale,” Journal of the American Academy of Dermatology, vol. 71, no. 4, pp. 760–763, 2014.
View at: Publisher Site | Google Scholar
J. Wilkin, M. Dahl, M. Detmar et al., “Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea,” Journal of the American Academy of Dermatology, vol. 50, no. 6, pp. 907–912, 2004.
View at: Publisher Site | Google Scholar
M. Schaller, L. M. C. Almeida, A. Bewley et al., “Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel,” British Journal of Dermatology, vol. 182, no. 5, pp. 1269–1276, 2020.
View at: Publisher Site | Google Scholar
F. Moustafa, R. S. Lewallen, and S. R. Feldman, “The psychological impact of rosacea and the influence of current management options,” Journal of the American Academy of Dermatology, vol. 71, no. 5, pp. 973–980, 2014.
View at: Publisher Site | Google Scholar
A. Bewley, J. Fowler, H. Schöfer, N. Kerrouche, and V. Rives, “Erythema of rosacea impairs health-related quality of life: results of a meta-analysis,” Dermatologic Therapy, vol. 6, no. 2, pp. 237–247, 2016.
View at: Publisher Site | Google Scholar
R. L. Gallo, R. D. Granstein, S. Kang et al., “Standard classification and pathophysiology of rosacea: the 2017 update by the national rosacea society expert committee,” Journal of the American Academy of Dermatology, vol. 78, no. 1, pp. 148–155, 2018.
View at: Publisher Site | Google Scholar
J. Tan, L. M. Almeida, A. Bewley et al., “Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel,” British Journal of Dermatology, vol. 176, no. 2, pp. 431–438, 2017.
View at: Publisher Site | Google Scholar
V. D. Schwab, M. Sulk, S. Seeliger et al., “Neurovascular and neuroimmune aspects in the pathophysiology of rosacea,” Journal of Investigative Dermatology Symposium Proceedings, vol. 15, no. 1, pp. 53–62, 2011.
View at: Publisher Site | Google Scholar
S. Seeliger, J. Buddenkotte, A. Schmidt-Choudhury et al., “Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo,” American Journal Of Pathology, vol. 177, no. 5, pp. 2563–2575, 2010.
View at: Publisher Site | Google Scholar
N. M. E. Carmichael, J. O. Dostrovsky, and M. P. Charlton, “Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin,” Pain, vol. 149, no. 2, pp. 316–324, 2010.
View at: Publisher Site | Google Scholar
E. M. Peters, M. E. Ericson, J. Hosoi et al., “Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance,” Journal of Investigative Dermatology, vol. 126, no. 9, pp. 1937–1947, 2006.
View at: Publisher Site | Google Scholar
K. R. Aoki, “Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A,” Neurotoxicology, vol. 26, no. 5, pp. 785–793, 2005.
View at: Publisher Site | Google Scholar
C. Morenilla-Palao, R. Planells-Cases, N. García-Sanz, and A. Ferrer-Montiel, “Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity,” Journal of Biological Chemistry, vol. 279, no. 24, pp. 25665–25672, 2004.
View at: Publisher Site | Google Scholar
J. E. Choi, T. Werbel, Z. Wang, C. C. Wu, T. L. Yaksh, and A. Di Nardo, “Botulinum toxin blocks mast cells and prevents rosacea like inflammation,” Journal of Dermatological Science, vol. 93, no. 1, pp. 58–64, 2019.
View at: Publisher Site | Google Scholar
E. Geddoa, H. E. Matar, and T. R. Paes, “The use of botulinum toxin-A in the management of neck and anterior chest wall flushing: pilot study,” International Journal of Dermatology, vol. 52, no. 12, pp. 1547–1550, 2013.
View at: Publisher Site | Google Scholar
K. Y. Park, H. J. Kwon, J. M. Kim et al., “A pilot study to evaluate the efficacy and safety of treatment with botulinum toxin in patients with recalcitrant and persistent erythematotelangiectatic rosacea,” Annals of Dermatology, vol. 30, no. 6, pp. 688–693, 2018.
View at: Publisher Site | Google Scholar
M. J. Kim, J. H. Kim, H. I. Cheon et al., “Assessment of skin physiology change and safety after intradermal injections with botulinum toxin: a randomized, double-blind, placebo-controlled, split-face pilot study in rosacea patients with facial erythema,” Dermatologic Surgery, vol. 45, no. 9, pp. 1155–1162, 2019.
View at: Publisher Site | Google Scholar
M. S. Lolis and D. J. Goldberg, “Radiofrequency in cosmetic dermatology: a review,” Dermatologic Surgery, vol. 38, no. 11, pp. 1765–1776, 2012.
View at: Publisher Site | Google Scholar
M. L. Elsaie and S. Choudhary, “Updates on the pathophysiology and management of acne rosacea,” Postgraduate Medicine, vol. 121, no. 5, pp. 178–186, 2009.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2023 Jin Seo Park et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

478

Downloads

270

Citations