Efficacy of Topical 2% Carteolol in the Treatment of Infantile Hemangiomas: A Dermoscopic and Clinical Evaluation

Efficacy of Topical 2% Carteolol in the Treatment of Infantile Hemangiomas: A Dermoscopic and Clinical Evaluation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Efficacy of Topical 2% Carteolol in the Treatment of Infantile Hemangiomas: A Dermoscopic and Clinical Evaluation Esranur Ünal, Muhammed Burak Yücel, Saadet Nurşah Gedikli, Yılmaz Ulaş, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5925739/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Infantile hemangiomas (IH) are the most common benign vascular tumors in infants, often requiring treatment in 10–15% of cases due to complications. While systemic propranolol is the first-line treatment, its potential for systemic side effects raises interest in topical therapies. This study investigates the efficacy of topical 2% carteolol in treating IH and its dermoscopic changes over time. Methods A total of 15 patients with IH were treated with topical 2% carteolol drops applied twice daily for 3 months. Clinical and dermoscopic images were captured at baseline, 1 month, and 3 months. Dermoscopic features such as erythema, clods, coiled vessels, dotted vessels, and others were evaluated. Visual Analog Scale (VAS) scores were used to assess treatment response. Results The most frequent dermoscopic findings at baseline were coiled vessels, followed by serpentine and dotted vessels. At 1 and 3 months, significant improvements were observed, with reductions in erythema and coiled vessel scores (p < 0.05) and at 3 months with reductions in clod score (p < 0.05). The skin-colored structureless area significantly increased, indicating lesion regression (p < 0.05). VAS scores showed a significant decrease over the 3-month period, with a positive correlation between baseline dotted vessel scores and treatment response (r:0.656, p:0.008). Conclusions Topical 2% carteolol is an effective and safe treatment for IH. Dermoscopic monitoring provides valuable insights into treatment progression, showing significant changes in erythema, clod, and vascular patterns. The presence of dotted vessels at baseline may serve as a predictor of a favorable treatment response. Further studies with longer follow-up are needed to validate these findings. Figures Figure 1 Introduction Haemangiomas are benign vascular neoplasms that arise from the proliferation of endothelial cells 1 . Infantile haemangiomas (IH) are the most common vascular tumours in infancy, occurring in approximately 5% of children with a higher prevalence in females and white individuals 2 , 3 . These lesions are usually not present at birth, initially manifesting as a slight halo and pale discoloration, becoming more pronounced during the first two weeks of life. IH are most commonly located in the head and neck region, accounting for 80% of cases 2 . Risk factors for IH include low birth weight multiple pregnancies, progesterone treatment, low gestational age, a family history of IH, intrauterine complications such as eclampsia and placental anomalies 2 , 3 . IH result from dysregulation of angiogenesis and vasculogenesis, but the precise triggers for IH development remain unclear 3 . Among various theories, the placental origin hypothesis is considered the most plausible. It is that prenatal or intrapartum defects in the placenta lead to the emergence of placenta-derived endothelial progenitor cells (EPCs) which participate in various pathways that contribute to IH formation influenced by intrinsic and extrinsic factors 4 . IH follows a distinct life cycle, including proliferation and involution phases. They usually appear within the first four weeks of life, with most lesions completing their growth by the fifth month. Involution starts around at 12 months of age and is usually complete by the age of 4. During involution, most lesions flatten and central regression 5 . IH are classified as superficial, deep, or mixed, depending on the depth of involvement during the proliferative phase. They are also categorized as focal, multifocal, or segmental based on their anatomical configuration. While most IH regress spontaneously in early childhood without significant sequelae, a small subgroup is at risk for complications. These may include local complications such as ulceration, bleeding, and pain, as well as more severe complications like visual or hearing impairment, airway obstruction, and congestive heart failure 4 , 6 , 7 . Even in cases with mild functional problems parents often express concern about cosmetic aspects, particularly because these lesions are usually in visible areas 8 . Systemic and topical β-blockers have been shown to be effective and safe for treating both complicated and uncomplicated haemangiomas and are considered first-line treatments in current literature. Topical β-blockers are recommended as the first choice for patients with thin, superficial focal IH and those with contraindications to systemic treatment 4 . Dermoscopically, IH exhibit polymorphic vascular structures, including dotted vessels, globular vessels, comma-like vessels, and linear vessels 9 . Out-of-focus dilated telangiectatic vessels may also be observed in the background. A typical dermoscopic finding is lacunae of varying sizes, which may appear red, red-brown, or red-blue in color. In deeper haemangiomas, a bluish background is more prominent, while a red background and white structureless area are seen in more superficial lesions 10 . In this study, we aimed to investigate dermoscopic changes during lesion involution in patients with IH treated with topical 2% carteolol drops and evaluate the relationship between clinical response and dermoscopic changes. Materials and Methods We recruited 17 patients with IH who visited the dermatology clinic at Kayseri City Hospital between January 2023 and January 2024. Two patients were excluded from the study due to non-compliance with the 3-month follow-up. Topical 2% carteolol drops were administered twice daily, with two drops applied to cover the entire lesion, followed by gentle massage. Clinical and dermoscopic images were recorded at baseline, after 1 month, and after 3 months using an ATBM Fotofinder®. Clinical photographs were used to analyze the changes in lesion size following treatment. Dermoscopically; erythema, clods, dotted vessels, coiled vessels, linear vessels, serpentine vessels, white and pink structureless areas, and skin-colored structureless areas under treatment. A score was assigned according to the density of dermoscopic structures (No structure: 0, 1–25%: 1, 26–50%: 2, 51–75%: 3, 76–100%: 4). Visual Analog Scale (VAS) was used to evaluate the clinical response to treatment in superficial hemangiomas. Color, longest diameter and thickness were assessed, with scores ranging from 0 to 3 for each parameter (No change: 0, Complete response: 3). If VAS was 0, 1–3, 4–6, 7–9; it was considered as no response, poor response, good response and, excellent response respectively 11 . To ensure objectivity, clinical and dermoscopic photographs taken at baseline, 1 month, and 3 months were independently evaluated by four blinded physicians not involved in the treatment process. These physicians scored the photographs according to predefined clinical and dermoscopic criteria. Patients with mucosal involvement, deep-type, multifocal or segmental haemangiomas, or those who did not attend follow-up were excluded from the study. Ethical approval for the study was obtained from the ethics committee on April 18, 2024 (File No. 64). Statistical analysis Statistical analysis was conducted using IBM SPSS Statistics for Windows (v.25). Quantitative variables were expressed as the mean ± standard deviation (SD) for normally distributed data or as the median (range) for non-normally distributed data. Normality of numerical variables was assessed using the Kolmogorov-Smirnov or Shapiro-Wilk tests. The relationships between continuous variables were analyzed using Pearson correlation for parametric data and Spearman correlation for non-parametric data. The relationship between numerical variables across different time points was evaluated using Repeated Measures ANOVA. Statistical significance was set at p < 0.05. Results Demographic and Clinical Features of the Study Population A total 15 IHs in 15 patients were included in the study. The female-to-male ratio was 4:1 and the mean age of the patients was 19,5 ± 13,8 months. The specific locations of the IHs were the head in 2 patients (13.3%), the upper extremities in 3 patients (20%), the lower extremities in 5 patients (33.3%) and, the trunk in 5 patients (33.3%). The median area of the lesions was 70.2 ± 77.7 cm². Coiled Vessel Score The mean coiled vessel score before treatment was 2.07 ± 1.53. This decreased to 1.27 ± 0.79 at 1 month and 0.67 ± 0.61 at 3 months. The coiled vessel score decreased significantly at both the 1st (p=0.016) and 3rd months (p=0.002) compared to baseline (Table 1). Dotted, Linear, and Serpentine Vessel Scores, and White and Pink Structureless Area Scores There was no statistically significant difference in the scores for dotted, linear, and serpentine vessels, or for white and pink structureless areas, between baseline, the 1st month, and the 3rd month (Table 1). Clod Score The mean clod score before treatment was 1.2 ± 1.5 (clod score: 0 in 9 patients, 2 in 1 patient, 3 in 4 patients, 4 in 1 patient). After 1 month, it decreased to 0.6 ± 1.1 (clod score was 0 in 11 patients, 2 in 1 patient, 3 in 1 patient and, 4 in 2 patients) and at 3 months, it was 0.2 ± 0.5 (clod score 0 in 13 patients, 2 in 1 patient and, 3 in 1 patient) at the end of 3rd month. The clod score decreased significantly at 3 months compared to baseline (p=0.031) (Table 1). Erythema Score The mean erythema score before treatment was 4 (erythema score of 4 in all 15 patients). After 1 month, it decreased to 3.13 ± 0.64 (erythema score: 2 in 2 patients, 3 in 9 patients, and 4 in 4 patients), and at 3 months, it was 2.13 ± 0.83 (erythema score: 2 in 4 patients, 3 in 5 patients, and 4 in 6 patients). Erythema scores decreased significantly at both 1 month (p<0.001) and 3 months (p<0.001) compared to baseline. Furthermore, erythema scores decreased significantly from the 1st to the 3rd month (p<0.001) (Table 1). Skin-Colored Structureless Area Score The mean skin coloured structureless area score before treatment was 0.8 ± 0.77. It increased to 1.33 ± 1.29 at 1 month and, 1.93 ± 1.71 at 3 months. The skin-coloured structureless area increased significantly at both 1 month (p=0.018) and 3 months (p=0.005) compared to baseline. Additionally, a significant increase was observed from the 1st to the 3rd month (p = 0.018) (Table 1). Erythema scores and skin-coloured structureless area scores at 3 months were negatively correlated (r:-0.695, p:0.004) (Table 2). Dermoscopic findings during treatment is shown in Figure 1. Visual Analog Scale and Correlation The VAS increased at both 1 month (0-1) and 3 months (0-3) compared to baseline (p=0.026, p<0.001, respectively) (Table 3). The VAS at both 1 month and 3 months was positively correlated with the dotted vessel score at baseline (r = 0.652, p = 0.008; r = 0.656, p = 0.008, respectively). Additionally, the 3rd-month VAS was negatively correlated with erythema at 3 months (r = -0.634, p = 0.011) (Table 2). Discussion Infantile hemangioma is the most common vascular tumor in infancy, typically presenting as a benign growth. However, approximately 10-15% of cases require treatment due to the risk of complications such as ulceration, bleeding, or obstruction of vital structures 4,12 . Although systemic propranolol is the current first-line treatment for IH, it is associated with potential systemic side effects, including hypoglycemia, bradycardia, hypotension, and electrolyte disturbances. In contrast, topical treatments, such as topical 2% carteolol, offer the advantage of localized action with minimal systemic absorption, reducing the likelihood of adverse effects 13,14 . Dermoscopy is a non-invasive imaging tool that allows detailed examination of skin lesions, making it particularly useful for assessing the vascular morphology and architecture of IH. This technique provides dermatologists with valuable information for the diagnosis and management of these lesions 15,16 . While there is limited literature on the dermoscopic features of IH, several studies have reported characteristic findings. Agrawal et al. identified irregular tortuous and arborizing vessels as the most common dermoscopic features in IH, while Gao et al. found serpentine and coiled vessels to be predominant 17,18 . Valdebran et al. observed that linear and clustered vascular structures correlated with higher involution rates in IH treated with topical timolol 19 . In a study by Tognetti et al. investigating dermoscopic changes in IHs under oral propranolol treatment, the most common dermoscopic feature observed was glomerular vessels. The predominant vascular structures at the 1st, 3rd, and 6th months of treatment were corkscrew, comma, and linear-irregular vessels, respectively. During the treatment period, a significant decrease in glomerular vessels was observed (p<0.05), while dotted vessels increased (p<0.05). Additionally, arborizing vessels were associated with relapse, whereas reticular patterns and linear-irregular vessels were more prominent in cases of persistent IH 20 . In our study, coiled vessels were the most frequently observed dermoscopic feature at baseline, followed by serpentine and dotted vessels. Over the course of treatment, the most prominent vascular structures at 1 and 3 months were serpentine vessels, while linear vessels were the least observed. These findings contribute to the growing body of knowledge on dermoscopic patterns in IH and their potential role in monitoring treatment response. Dermoscopy of IH typically reveals red lacunae and a red, red-blue, or red-white background 18 .In a case report by Jassi et al., clods and vascular structures were observed in parallel with lesion flattening during topical timolol treatment 21 . As IH progresses from the proliferative phase, characterized by compact capillary structures with high mitotic activity, to the involution phase, the vascular pattern becomes more prominent, with endothelial cells flattening. This transition explains the significant decrease in clod structures observed in our study after 3 months of treatment, consistent with the expected histopathological changes in IH 22,23 . The reduction in erythema is one of the most well-documented effects of β-blocker therapy in IH 19,24 .This decrease in erythema has been histologically linked to the disappearance of lesional capillaries and a corresponding reduction in vascular density 5,19 . Topical propranolol has been shown to decrease vascular endothelial growth factor (VEGF) levels, which in turn suppresses the proliferative effects of this factor and contributes to erythema reduction 14 . In our study, erythema scores decreased significantly both at 1 month and 3 months compared to baseline (p< 0.05), corroborating findings from other studies on the efficacy of β-blockers in reducing erythema in IH. As hemangiomas regress, they typically exhibit changes such as the appearance of brown areas, white hair, comedo-like openings, and faint white spots at the center of the lesion 17 . These changes reflect the involution process, during which mitotic activity decreases, and vascular tissue is gradually replaced by fibrous and fatty tissue. This process often leads to fibrosis, which becomes more prominent with further involution 22,23 . In line with this, our study observed a significant increase in skin-colored structureless area scores at both 1 and 3 months of treatment, which serves as an indicator of lesion regression. Various visual grading systems, such as Achauer's method, the VAS, and the Infantile Hemangioma Activity Score (HAS), have been developed to assess treatment efficacy in IH 25 . In our study, we utilized the VAS, which demonstrated a significant reduction in lesion size and activity at both the 1st and 3rd months of treatment compared to baseline (p = 0.026, p <0.001, respectively). These results suggest that topical carteolol is an effective treatment for IH. Additionally, we found a significant negative correlation between VAS scores at 3 months and erythema at 3 months (r = -0.634, p = 0.011), highlighting the importance of erythema reduction as a key parameter in evaluating treatment response. Furthermore, a positive correlation was observed between VAS scores at 1 and 3 months and baseline dotted vessel scores (r = 0.656, p = 0.008). This suggests that the presence of a higher number of dotted vessels at baseline may serve as a predictive marker for a better treatment response. The limitations of our study are relatively small sample size and the lack of long-term follow-up data that are important factors to consider. Future studies with larger cohorts and extended follow-up periods are needed to further validate our findings and assess the long-term efficacy and safety of topical carteolol in the management of IH. In conclusion, topical 2% carteolol appears to be a safe and effective treatment for IH. Dermoscopic evaluation reveals significant changes in erythema, clod, and coiled vessel scores, with a notable increase in skin-colored structureless areas, indicative of lesion regression. Monitoring these dermoscopic features during treatment can provide essential guidance for clinical follow-up. Furthermore, the reduction in erythema and the presence of dotted vessels at baseline may serve as important predictors of treatment response. Recording dermoscopic features throughout the treatment period can aid clinicians in assessing treatment progress and guide future research into predictive markers for IH management. Declarations *Funding sources: Intramural funding *Conflict of interest: Unal E, Yucel MB, Gedikli SN, Ulaş Y, Mutlu FT and Akay BN do not have any conflict of interest to report. Ethical Approval: Ethical approval for the study was obtained from the ethics committee on April 18, 2024 (File No. 64). Ethics statement: The patients in this manuscript have given written informed consent to the publication of their case details Data availability statement : The data that support the findings of this study are available from the corresponding author upon reasonable request. *Author Contributions: Esranur Ünal: The study concept and design, the physician who examines the patient, takes dermoscopic photographs, writing of the manuscript, critical review of the literature Muhammed B. Yücel: The physician who examines the patient, writing of the manuscript Saadet N. Gedikli: The physician who examines the patient, takes dermoscopic photographs Yılmaz Ulaş: The physician who examines the patient Fatma T. Mutlu: The physician who examines the patient Bengü N. Akay: Critical review of important intellectual content, final approval of the final version of the manuscript References Kita AE, Long JL, Hemangioma (2016) Ear Nose Throat J. ;95(1) Kowalska M, Dębek W, Matuszczak E (2021) Infantile hemangiomas: An update on pathogenesis and treatment. 10, J Clin Med Léauté-Labrèze C, Harper JI, Hoeger PH (2017) Infantile haemangioma. 390, Lancet Tiemann L, Hein S (2020) Infantile hemangioma: A review of current pharmacotherapy treatment and practice pearls. 25, J Pediatr Pharmacol Ther Darrow DH, Greene AK, Mancini AJ, Nopper AJ, Cohen BA, Antaya RJ et al (2015) Diagnosis and management of infantile Hemangioma. Pediatrics. ;136(4) Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA et al (2006) Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment. Pediatrics. ;118(3) Nazemian S, Sharif S, Childers ELB (2023) Infantile Hemangioma: A Common Lesion in a Vulnerable Population. 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Tables Table 1: Coiled, dotted, linear, serpentine vessel, clod, erythema, white structureless area and skin color structureless area score Coiled Vessel Mean Difference p* 0–1. month 0.4 (1.87 ± 1.45 – 1.47 ± 1.11) 0.635 0–3. month 0.8 (1.87 ± 1.45 – 1.07 ± 0.79) 0.183 1–3. month 0.4 (1.47 ± 1.11- 1.07 ± 0.79) 0.635 Dotted Vessel Mean Difference p* 0–1. month 0.067 (0.73 ± 1.1 – 0.8 ± 0.8) 0.388 0–3. month 0.2 (0.73 ± 1.1 – 0.53 ± 0.64) 0.344 1–3. month 0.267 (0.8 ± 0.8 - 0.53 ± 0.64 0.255 Linear Vessel Mean Difference p* 0–1. month 0.4 (0.27 ± 0.45 – 0.27 ± 0.45) 1 0–3. month 0.8 (0.27 ± 0.45 – 0.33 ± 0.48) 1 1–3. month 0.4 (0.27 ± 0.45- 0.33 ± 0.48) 1 Serpentine Vessel Mean Difference p* 0–1. month 0.47 (1.4 ± 1.24 – 1.87 ± 0.99) 0.611 0–3. month 0.2 (1.4 ± 1.24 – 1.6 ± 0.98) 1 1– 3. month 0.467 (1.87 ± 0.99- 1.87 ± 0.99) 0.611 Erythema Mean Differences p* 0–1. month 0.867 (4.0- 3.13 ± 0.6) <.001 0–3. month 1.867 (4.0- 2.13 ± 0.8) <.001 1–3. month 1 (3.13 ± 0.6- 2.13 ± 0.8) .003 Clod Mean Difference p* 0–1. month 0.6 (1.2 ± 1.5 – 0.6 ± 1.1) 0.1 0–3. month 1 (1.2 ± 1.5 – 0.2 ± 0.5) 0.031 1–3. month 0.4 (0.6 ± 1.1- 0.2 ± 0.5) 0.247 White Structureless Areas Mean Difference p* 0–1. month 0.267 (0.4 ± 0.5 – 0.67 ± 0.9) 0.122 0–3. month 1.467 (0.4 ± 0.5 – 0.87 ± 1.24) 0.144 Skin Coloured Structureless Area Mean Difference p* 0–1. month 0.533 (0.8 ± 0.77 – 1.33 ± 1.29) 0.018 0–3. month 1.133 (0.8 ± 0.77 – 1.93 ± 1.71) 0.005 1–3. month 0.6 (1.33 ± 1.29- 1.93 ± 1.71) 0.018 *Repeated Measure ANOVA Test Table 2: Correlation analysis of variables 1st month erythema 3rd month erythema Dotted vessel at baseline 1st month skin color structureless area 3rd month skin color structureless area 1st month white structureless area 3rd month white structureless area Visual Activity Scale 0-1 month Visual Activity Scale 1-3 month Visual Activity Scale 0-3 month 1st month erythema 3rd month erythema r:0,232 p:0.405 Dotted vessel at baseline r:-0,555 p:0.032 r:-0,348 p:0.204 1st month skin color structureless area r:-0,317 p:0.25 r:-0,509 p:0.053 r:0,319 p:0.247 3rd month skin color structureless area r: -0,187 p: 0.504 r:-0,695 ** p:0.004 r:0,332 p:0.227 r:0,917 ** p:0.000 1st month white structureless area r: 0,083 p:0.77 r:0,444 p:0.097 r: -0,168 p:0,548 r:0-,820 ** p:0.000 r:-0,898 ** p:0.000 3rd month white structureless area r: 0,113 p:0,687 r: 0,362 p:0.185 r: -0,132 p:0,639 r:-0,770 ** p:0.000 r:-0,843 ** p:0.000 r:0,977 ** p:0.000 Visual Activity Scale 0-1 month r: -0,402 p:0,138 r: -0,552* p:0,033 r:0,652** p:0.008 r: 0,367 p:0,179 r: 0,491 p:0,063 r: -0,301 p:0,276 r: -0,282 p:0,308 Visual Activity Scale 1-3 month r: -0,231 p:0,408 r: -0,675** p:0,006 r:0,143 p:0.612 r: 0,357 p:0,191 r: 0,448 p:0,094 r: -0,359 p:0,189 r: -0,326 p:0,236 r: 0,367 p:0,179 Visual Activity Scale 0-3 month r: -0,477 p:0,072 r: -0,634** p:0,011 r:0,656** p:0.008 r: 0,317 p:0,25 r: 0,448 p:0,094 r: -0,331 p:0,228 r: -0,293 p:0,290 r: 0,719** p:0,003 r: 0,663** p:0,007 Pearson correlation analysis **. Correlation is significant at the 0.01 level (2-tailed). *. Correlation is significant at the 0.05 level (2-tailed). Table 3: Visual Analog Scale Visual Analogue Scale Mean Differences p* 0–1. month 0.4 (1.13 ± 0.35- 1.53 ± 0.51) 0.026 0–3. month 0.733 (1.13 ± 0.35- 1.87 ± 0.64) <.001 1–3. month 0.34 (1.53 ± 0.51- 1.87 ± 0.64) 0.058 *Repeated Measures ANOVA Test Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 18 Mar, 2025 Reviewers agreed at journal 18 Mar, 2025 Reviewers agreed at journal 15 Mar, 2025 Reviewers agreed at journal 15 Mar, 2025 Reviewers invited by journal 04 Feb, 2025 Editor assigned by journal 31 Jan, 2025 Submission checks completed at journal 31 Jan, 2025 First submitted to journal 29 Jan, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5925739","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":409490191,"identity":"9a928c8d-f6c0-4263-b781-b6c194fca0aa","order_by":0,"name":"Esranur Ünal","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYBADOcZm5gNA2kIOxDvwgAgtxsztbAlAWsIYrCWBCC2J7f08BiAtiQ0gLj4t/PxnH34ubLuX2NvMYyZdUCORPj/s8EOgLXZyug3YtUjOSDeWntlWbDyzma1MesYxidyNt9MMgFqSjc0OYNdicIONQZq3LUF2YzPzNmkeNqCW2QkgLQcSt+HQYn/+GPNvoBbG/YcZzKR5/kmkG85O/4BXiwFDGhvIFsXGZhYzIEMiQV46B78tEjfS2Kx5ziUYMzazJVvz9kkYbpDOKTiQYIDbL/z9x5hv85QlyDH2Hz54m+ebjbz87PTNHz5U2Mnh0oLFqQcgDiYByDeQonoUjIJRMApGAgAAt+ZZlY1bdPgAAAAASUVORK5CYII=","orcid":"","institution":"Department of Dermatology, Kayseri City Hospital","correspondingAuthor":true,"prefix":"","firstName":"Esranur","middleName":"","lastName":"Ünal","suffix":""},{"id":409490192,"identity":"149364d3-7ff8-4ce9-a136-697978b67de2","order_by":1,"name":"Muhammed Burak Yücel","email":"","orcid":"","institution":"Department of Dermatology, Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Muhammed","middleName":"Burak","lastName":"Yücel","suffix":""},{"id":409490194,"identity":"ff0b6826-9241-4f00-9295-89dd85979b39","order_by":2,"name":"Saadet Nurşah Gedikli","email":"","orcid":"","institution":"Department of Dermatology, Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Saadet","middleName":"Nurşah","lastName":"Gedikli","suffix":""},{"id":409490195,"identity":"01dac16c-201e-470b-93a3-ad7b614c6703","order_by":3,"name":"Yılmaz Ulaş","email":"","orcid":"","institution":"Department of Dermatology, Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yılmaz","middleName":"","lastName":"Ulaş","suffix":""},{"id":409490198,"identity":"a8b9abc8-a3cf-474d-975a-1206d9d1bbf7","order_by":4,"name":"Fatma Türkan Mutlu","email":"","orcid":"","institution":"Department of Pediatric Hematology and Oncology, Kayseri City Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Türkan","lastName":"Mutlu","suffix":""},{"id":409490200,"identity":"f80db374-2c7d-462c-970b-955540226c8d","order_by":5,"name":"Bengü Nisa Akay","email":"","orcid":"","institution":"Department of Dermatology, Ankara University, Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bengü","middleName":"Nisa","lastName":"Akay","suffix":""}],"badges":[],"createdAt":"2025-01-29 17:08:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5925739/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5925739/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75411603,"identity":"9d016a09-aa21-44a9-a08b-64b3dbab560c","added_by":"auto","created_at":"2025-02-04 09:11:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":741137,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Baseline: Red background with dotted and serpentine vessels (B) 1-month follow-up: Lesion flattened with decreased erythema, dotted and serpentine vessels (C) 3-month follow-up: Erythema resolved, increased skin-coloured structureless area and decreased dotted and serpentine vessels. (D)Baseline: Red background with coiled and dotted vessels (E): 1-month follow-up: Decreased erythema and coiled vessels, with an increase in serpentine vessels (F): 3-month follow-up: Lesion flattened, erythema resolved, increased skin coloured structureless area, decreased serpentine and coiled vessels\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5925739/v1/3f32cbbb3b5729f611f25f64.png"},{"id":75411604,"identity":"95ffe984-9b7d-4e2c-b641-1b7dc397ed70","added_by":"auto","created_at":"2025-02-04 09:11:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2391104,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5925739/v1/c84a747a-06c7-4ce4-8a19-59b8121da427.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Topical 2% Carteolol in the Treatment of Infantile Hemangiomas: A Dermoscopic and Clinical Evaluation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHaemangiomas are benign vascular neoplasms that arise from the proliferation of endothelial cells\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Infantile haemangiomas (IH) are the most common vascular tumours in infancy, occurring in approximately 5% of children with a higher prevalence in females and white individuals\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. These lesions are usually not present at birth, initially manifesting as a slight halo and pale discoloration, becoming more pronounced during the first two weeks of life. IH are most commonly located in the head and neck region, accounting for 80% of cases\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Risk factors for IH include low birth weight multiple pregnancies, progesterone treatment, low gestational age, a family history of IH, intrauterine complications such as eclampsia and placental anomalies\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIH result from dysregulation of angiogenesis and vasculogenesis, but the precise triggers for IH development remain unclear\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Among various theories, the placental origin hypothesis is considered the most plausible. It is that prenatal or intrapartum defects in the placenta lead to the emergence of placenta-derived endothelial progenitor cells (EPCs) which participate in various pathways that contribute to IH formation influenced by intrinsic and extrinsic factors\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. IH follows a distinct life cycle, including proliferation and involution phases. They usually appear within the first four weeks of life, with most lesions completing their growth by the fifth month. Involution starts around at 12 months of age and is usually complete by the age of 4. During involution, most lesions flatten and central regression\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIH are classified as superficial, deep, or mixed, depending on the depth of involvement during the proliferative phase. They are also categorized as focal, multifocal, or segmental based on their anatomical configuration. While most IH regress spontaneously in early childhood without significant sequelae, a small subgroup is at risk for complications. These may include local complications such as ulceration, bleeding, and pain, as well as more severe complications like visual or hearing impairment, airway obstruction, and congestive heart failure\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Even in cases with mild functional problems parents often express concern about cosmetic aspects, particularly because these lesions are usually in visible areas\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSystemic and topical β-blockers have been shown to be effective and safe for treating both complicated and uncomplicated haemangiomas and are considered first-line treatments in current literature. Topical β-blockers are recommended as the first choice for patients with thin, superficial focal IH and those with contraindications to systemic treatment\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Dermoscopically, IH exhibit polymorphic vascular structures, including dotted vessels, globular vessels, comma-like vessels, and linear vessels\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Out-of-focus dilated telangiectatic vessels may also be observed in the background. A typical dermoscopic finding is lacunae of varying sizes, which may appear red, red-brown, or red-blue in color. In deeper haemangiomas, a bluish background is more prominent, while a red background and white structureless area are seen in more superficial lesions\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to investigate dermoscopic changes during lesion involution in patients with IH treated with topical 2% carteolol drops and evaluate the relationship between clinical response and dermoscopic changes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eWe recruited 17 patients with IH who visited the dermatology clinic at Kayseri City Hospital between January 2023 and January 2024. Two patients were excluded from the study due to non-compliance with the 3-month follow-up.\u003c/p\u003e \u003cp\u003eTopical 2% carteolol drops were administered twice daily, with two drops applied to cover the entire lesion, followed by gentle massage. Clinical and dermoscopic images were recorded at baseline, after 1 month, and after 3 months using an ATBM Fotofinder\u0026reg;.\u003c/p\u003e \u003cp\u003eClinical photographs were used to analyze the changes in lesion size following treatment. Dermoscopically; erythema, clods, dotted vessels, coiled vessels, linear vessels, serpentine vessels, white and pink structureless areas, and skin-colored structureless areas under treatment. A score was assigned according to the density of dermoscopic structures (No structure: 0, 1\u0026ndash;25%: 1, 26\u0026ndash;50%: 2, 51\u0026ndash;75%: 3, 76\u0026ndash;100%: 4).\u003c/p\u003e \u003cp\u003eVisual Analog Scale (VAS) was used to evaluate the clinical response to treatment in superficial hemangiomas. Color, longest diameter and thickness were assessed, with scores ranging from 0 to 3 for each parameter (No change: 0, Complete response: 3). If VAS was 0, 1\u0026ndash;3, 4\u0026ndash;6, 7\u0026ndash;9; it was considered as no response, poor response, good response and, excellent response respectively\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo ensure objectivity, clinical and dermoscopic photographs taken at baseline, 1 month, and 3 months were independently evaluated by four blinded physicians not involved in the treatment process. These physicians scored the photographs according to predefined clinical and dermoscopic criteria.\u003c/p\u003e \u003cp\u003ePatients with mucosal involvement, deep-type, multifocal or segmental haemangiomas, or those who did not attend follow-up were excluded from the study. Ethical approval for the study was obtained from the ethics committee on April 18, 2024 (File No. 64).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was conducted using IBM SPSS Statistics for Windows (v.25). Quantitative variables were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for normally distributed data or as the median (range) for non-normally distributed data. Normality of numerical variables was assessed using the Kolmogorov-Smirnov or Shapiro-Wilk tests. The relationships between continuous variables were analyzed using Pearson correlation for parametric data and Spearman correlation for non-parametric data. The relationship between numerical variables across different time points was evaluated using Repeated Measures ANOVA. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemographic and Clinical Features of the Study Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total 15 IHs in 15 patients were included in the study. The female-to-male ratio was 4:1 and the mean age of the patients was 19,5 \u0026plusmn; 13,8 months. The specific locations of the IHs were the head in 2 patients (13.3%), the upper extremities in 3 patients (20%), the lower extremities in 5 patients (33.3%) and, the trunk in 5 patients (33.3%). The median area of the lesions was 70.2 \u0026plusmn; 77.7 cm\u0026sup2;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCoiled Vessel Score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean coiled vessel score before treatment was 2.07 \u0026plusmn; 1.53. This decreased to 1.27 \u0026plusmn; 0.79 at 1 month and 0.67 \u0026plusmn; 0.61 at 3 months. The coiled vessel score decreased significantly at both the 1st (p=0.016) and 3rd months (p=0.002) compared to baseline (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDotted, Linear, and Serpentine Vessel Scores, and White and Pink Structureless Area Scores\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no statistically significant difference in the scores for dotted, linear, and serpentine vessels, or for white and pink structureless areas, between baseline, the 1st month, and the 3rd month\u0026nbsp;(Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClod Score\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean clod score before treatment was 1.2 \u0026plusmn; 1.5 (clod score: 0 in 9 patients, 2 in 1 patient, 3 in 4 patients, 4 in 1 patient). After 1 month, it decreased to 0.6 \u0026plusmn; 1.1 (clod score was 0 in 11 patients, 2 in 1 patient, 3 in 1 patient and, 4 in 2 patients) and at 3 months, it was 0.2 \u0026plusmn; 0.5 (clod score 0 in 13 patients, 2 in 1 patient and, 3 in 1 patient) at the end of 3rd month. The clod score decreased significantly at 3 months compared to baseline (p=0.031)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eErythema Score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean erythema score before treatment was 4 (erythema score of 4 in all 15 patients). After 1 month, it decreased to 3.13 \u0026plusmn; 0.64 (erythema score: 2 in 2 patients, 3 in 9 patients, and 4 in 4 patients), and at 3 months, it was 2.13 \u0026plusmn; 0.83 (erythema score: 2 in 4 patients, 3 in 5 patients, and 4 in 6 patients). Erythema scores decreased significantly at both 1 month (p\u0026lt;0.001) and 3 months (p\u0026lt;0.001) compared to baseline. Furthermore, erythema scores decreased significantly from the 1st to the 3rd month (p\u0026lt;0.001) (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSkin-Colored Structureless Area Score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean skin coloured structureless area score before treatment was 0.8 \u0026plusmn; 0.77. It increased to 1.33 \u0026plusmn; 1.29 at 1 month and, 1.93 \u0026plusmn; 1.71 at 3 months. The skin-coloured structureless area increased significantly at both 1 month (p=0.018) and 3 months (p=0.005) compared to baseline.\u0026nbsp;Additionally, a significant increase was observed from the 1st to the 3rd month (p = 0.018) (Table 1). Erythema scores and skin-coloured structureless area scores at 3 months were negatively correlated (r:-0.695, p:0.004) (Table 2).\u003c/p\u003e\n\u003cp\u003eDermoscopic findings during treatment is shown in Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisual Analog Scale and Correlation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe VAS increased at both 1 month (0-1) and 3 months (0-3) compared to baseline (p=0.026, p\u0026lt;0.001, respectively) (Table 3). The VAS at both 1 month and 3 months was positively correlated with the dotted vessel score at baseline (r = 0.652, p = 0.008; r = 0.656, p = 0.008, respectively). Additionally, the 3rd-month VAS was negatively correlated with erythema at 3 months (r = -0.634, p = 0.011) (Table 2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eInfantile hemangioma is the most common vascular tumor in infancy, typically presenting as a benign growth. However, approximately 10-15% of cases require treatment due to the risk of complications such as ulceration, bleeding, or obstruction of vital structures\u003csup\u003e4,12\u003c/sup\u003e. Although systemic propranolol is the current first-line treatment for IH, it is associated with potential systemic side effects, including hypoglycemia, bradycardia, hypotension, and electrolyte disturbances. In contrast, topical treatments, such as topical 2% carteolol, offer the advantage of localized action with minimal systemic absorption, reducing the likelihood of adverse effects\u003csup\u003e13,14\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDermoscopy is a non-invasive imaging tool that allows detailed examination of skin lesions, making it particularly useful for assessing the vascular morphology and architecture of IH. This technique provides dermatologists with valuable information for the diagnosis and management of these lesions\u003csup\u003e15,16\u003c/sup\u003e. While there is limited literature on the dermoscopic features of IH, several studies have reported characteristic findings. Agrawal et al. identified irregular tortuous and arborizing vessels as the most common dermoscopic features in IH, while Gao et al. found serpentine and coiled vessels to be predominant\u003csup\u003e17,18\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eValdebran et al. observed that linear and clustered vascular structures correlated with higher involution rates in IH treated with topical timolol\u003csup\u003e19\u003c/sup\u003e. In a study by Tognetti et al. investigating dermoscopic changes in IHs under oral propranolol treatment, the most common dermoscopic feature observed was glomerular vessels. The predominant vascular structures at the 1st, 3rd, and 6th months of treatment were corkscrew, comma, and linear-irregular vessels, respectively. During the treatment period, a significant decrease in glomerular vessels was observed (p\u0026lt;0.05), while dotted vessels increased (p\u0026lt;0.05). Additionally, arborizing vessels were associated with relapse, whereas reticular patterns and linear-irregular vessels were more prominent in cases of persistent IH\u003csup\u003e20\u003c/sup\u003e.\u0026nbsp;In our study, coiled vessels were the most frequently observed dermoscopic feature at baseline, followed by serpentine and dotted vessels. Over the course of treatment, the most prominent vascular structures at 1 and 3 months were serpentine vessels, while linear vessels were the least observed. These findings contribute to the growing body of knowledge on dermoscopic patterns in IH and their potential role in monitoring treatment response.\u003c/p\u003e\n\u003cp\u003eDermoscopy of IH typically reveals red lacunae and a red, red-blue, or red-white background\u003csup\u003e18\u003c/sup\u003e.In a case report by Jassi et al., clods and vascular structures were observed in parallel with lesion flattening during topical timolol treatment\u003csup\u003e21\u003c/sup\u003e. As IH progresses from the proliferative phase, characterized by compact capillary structures with high mitotic activity, to the involution phase, the vascular pattern becomes more prominent, with endothelial cells flattening. This transition explains the significant decrease in clod structures observed in our study after 3 months of treatment, consistent with the expected histopathological changes in IH\u003csup\u003e22,23\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe reduction in erythema is one of the most well-documented effects of \u0026beta;-blocker therapy in IH \u003csup\u003e19,24\u003c/sup\u003e.This decrease in erythema has been histologically linked to the disappearance of lesional capillaries and a corresponding reduction in vascular density\u003csup\u003e5,19\u003c/sup\u003e. Topical propranolol has been shown to decrease vascular endothelial growth factor (VEGF) levels, which in turn suppresses the proliferative effects of this factor and contributes to erythema reduction \u003csup\u003e14\u003c/sup\u003e. In our study, erythema scores decreased significantly both at 1 month and 3 months compared to baseline (p\u0026lt; 0.05), corroborating findings from other studies on the efficacy of \u0026beta;-blockers in reducing erythema in IH.\u003c/p\u003e\n\u003cp\u003eAs hemangiomas regress, they typically exhibit changes such as the appearance of brown areas, white hair, comedo-like openings, and faint white spots at the center of the lesion\u003csup\u003e17\u003c/sup\u003e. These changes reflect the involution process, during which mitotic activity decreases, and vascular tissue is gradually replaced by fibrous and fatty tissue. This process often leads to fibrosis, which becomes more prominent with further involution\u003csup\u003e22,23\u003c/sup\u003e. \u0026nbsp;In line with this, our study observed a significant increase in skin-colored structureless area scores at both 1 and 3 months of treatment, which serves as an indicator of lesion regression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVarious visual grading systems, such as Achauer\u0026apos;s method, the VAS, and the Infantile Hemangioma Activity Score (HAS), have been developed to assess treatment efficacy in IH\u003csup\u003e25\u003c/sup\u003e. \u0026nbsp;In our study, we utilized the VAS, which demonstrated a significant reduction in lesion size and activity at both the 1st and 3rd months of treatment compared to baseline (p = 0.026, p \u0026lt;0.001, respectively). These results suggest that topical carteolol is an effective treatment for IH. Additionally, we found a significant negative correlation between VAS scores at 3 months and erythema at 3 months (r = -0.634, p = 0.011), highlighting the importance of erythema reduction as a key parameter in evaluating treatment response. Furthermore, a positive correlation was observed between VAS scores at 1 and 3 months and baseline dotted vessel scores (r = 0.656, p = 0.008). This suggests that the presence of a higher number of dotted vessels at baseline may serve as a predictive marker for a better treatment response.\u003c/p\u003e\n\u003cp\u003eThe limitations of our study are\u0026nbsp;relatively small sample size and the lack of long-term follow-up data that are important factors to consider. Future studies with larger cohorts and extended follow-up periods are needed to further validate our findings and assess the long-term efficacy and safety of topical carteolol in the management of IH.\u003c/p\u003e\n\u003cp\u003eIn conclusion, topical 2% carteolol appears to be a safe and effective treatment for IH. Dermoscopic evaluation reveals significant changes in erythema, clod, and coiled vessel scores, with a notable increase in skin-colored structureless areas, indicative of lesion regression. Monitoring these dermoscopic features during treatment can provide essential guidance for clinical follow-up. Furthermore, the reduction in erythema and the presence of dotted vessels at baseline may serve as important predictors of treatment response. Recording dermoscopic features throughout the treatment period can aid clinicians in assessing treatment progress and guide future research into predictive markers for IH management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e*Funding sources:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIntramural funding\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*Conflict of interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnal E, Yucel MB, Gedikli SN, Ulaş Y, Mutlu FT and Akay BN do not have any conflict of interest to report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval:\u003c/strong\u003e Ethical approval for the study was obtained from the ethics committee on April 18, 2024 (File No. 64).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement:\u003c/strong\u003e The patients in this manuscript have given written informed consent to the publication of their case details\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e: The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e*Author Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEsranur \u0026Uuml;nal:\u003c/strong\u003e \u003cstrong\u003eThe study concept and design,\u0026nbsp;\u003c/strong\u003ethe physician who examines the patient, takes dermoscopic photographs, writing of the manuscript, critical review of the literature\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMuhammed B. Y\u0026uuml;cel:\u003c/strong\u003e The physician who examines the patient,\u0026nbsp;writing of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSaadet N. Gedikli:\u003c/strong\u003e The physician who examines the patient, takes dermoscopic photographs\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYılmaz Ulaş:\u003c/strong\u003e The physician who examines the patient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFatma T. Mutlu:\u003c/strong\u003e The physician who examines the patient\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBeng\u0026uuml; N. Akay:\u0026nbsp;\u003c/strong\u003eCritical review of important intellectual content, \u003cstrong\u003efinal approval of the final version of the manuscript\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKita AE, Long JL, Hemangioma (2016) Ear Nose Throat J. ;95(1)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKowalska M, Dębek W, Matuszczak E (2021) Infantile hemangiomas: An update on pathogenesis and treatment. 10, J Clin Med\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026eacute;aut\u0026eacute;-Labr\u0026egrave;ze C, Harper JI, Hoeger PH (2017) Infantile haemangioma. 390, Lancet\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiemann L, Hein S (2020) Infantile hemangioma: A review of current pharmacotherapy treatment and practice pearls. 25, J Pediatr Pharmacol Ther\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDarrow DH, Greene AK, Mancini AJ, Nopper AJ, Cohen BA, Antaya RJ et al (2015) Diagnosis and management of infantile Hemangioma. Pediatrics. ;136(4)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, Horii KA et al (2006) Prospective study of infantile hemangiomas: Clinical characteristics predicting complications and treatment. Pediatrics. ;118(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNazemian S, Sharif S, Childers ELB (2023) Infantile Hemangioma: A Common Lesion in a Vulnerable Population. Int J Environ Res Public Health. ;20(8)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagata E, Kashiwagura Y, Okada E, Tanaka S, Sano S, Nishida M et al (2022) Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study. J Pharmacol Sci. ;149(2)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOiso N, Kawada A (2011) The dermoscopic features in infantile hemangioma. Pediatr Dermatol. ;28(5)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeri I, Orioni G, Leuzzi M, Facchini E, Mengozzi E, Chessa MA (2024) Infantile Hemangioma with Minimal or Arrested Growth (IHMAG): A Retrospective Analysis of Clinical and Dermoscopic Diagnostic Clues. Dermatol Pract Concept. ;14(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung HL (2021) Update on infantile hemangioma. Vol. 64, Clinical and Experimental Pediatrics\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026eacute;aut\u0026eacute;-Labr\u0026egrave;ze C, Prey S, Ezzedine K (2011) Infantile haemangioma: Part II. Risks, complications and treatment. J Eur Acad Dermatol Venereol. ;25(11)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoeger PH, Harper JI, Baselga E, Bonnet D, Boon LM, Atti MCD et al (2015) Treatment of infantile haemangiomas: recommendations of a European expert group. 174, Eur J Pediatrics\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrice A, Rai S, Mcleod RWJ, Birchall JC, Elhassan HA (2018) Topical propranolol for infantile haemangiomas: a systematic review. 32, J Eur Acad Dermatol Venereol\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeber P, Tschandl P, Sinz C, Kittler H (2018) Dermatoscopy of Neoplastic Skin Lesions: Recent Advances, Updates, and Revisions, vol 19. Current Treatment Options in Oncology\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOiso N, Kimura M, Kawara S, Kawada A (2011) Clinical, dermoscopic, and histopathologic features in a case of infantile hemangioma without proliferation. Pediatr Dermatol. ;28(1)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgrawal N, Mehta HH, Lakhotia R, Prakashey AR (2024) Dermoscopy of Cutaneous Vascular Lesions: An Observational Study. Clin Dermatology Rev. ;8(1)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao J, Fei W, Shen C, Shen X, Sun M, Xu N et al (2021) Dermoscopic Features Summarization and Comparison of Four Types of Cutaneous Vascular Anomalies. Front Med (Lausanne). ;8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValdebran M, Elbendary A, Choi F, Kittler H, Kelly KM (2020) Dermoscopic features of infantile hemangioma during treatment with topical propranolol. JAAD Int. ;1(2)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTognetti L, Pianigiani E, Ierardi F, Cartocci A, Fiorani D, de Quattro M et al (2020) A new clinical and dermoscopic monitoring of infantile hemangiomas treated with oral propranolol. Dermatol Ther. ;33(6)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJassi R, Sanke S, Chander R (2020) Dermoscopic Evaluation of Infantile Hemangioma Treated With Topical Timolol. Dermatol Pract Concept\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTan ST, Velickovic M, Ruger BM, Davis PF (2000) Cellular and Extracellular Markers of Hemangioma. Plast Reconstr Surg. ;106(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCallahan AB, Yoon MK (2012) Infantile hemangiomas: A review. Saudi J Ophthalmol. ;26(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDermoscopic findings during the (2018) course of β-blocker treatment for infantile hemangioma. J Am Acad Dermatol. ;79(3)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie M, Liu J, Zhou P, Xu X, Liu H, Zeng L et al (2023) Development of a digital imaging analysis system to evaluate the treatment response in superficial infantile hemangiomas. PLoS ONE. ;18(3 March).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Coiled, dotted, linear, serpentine vessel, clod, erythema, white structureless area and skin color structureless area score\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoiled Vessel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.4 (1.87 \u0026plusmn; 1.45 \u0026ndash; 1.47 \u0026plusmn; 1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.8 (1.87 \u0026plusmn; 1.45 \u0026ndash; 1.07 \u0026plusmn; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.4 (1.47 \u0026plusmn; 1.11- 1.07 \u0026plusmn; 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.635\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDotted Vessel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.067 (0.73 \u0026plusmn; 1.1 \u0026ndash; 0.8 \u0026plusmn; 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.388\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.2 (0.73 \u0026plusmn; 1.1 \u0026ndash; 0.53 \u0026plusmn; 0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.344\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.267 (0.8 \u0026plusmn; 0.8 - 0.53 \u0026plusmn; 0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLinear Vessel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.4 (0.27 \u0026plusmn; 0.45 \u0026ndash; 0.27 \u0026plusmn; 0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.8 (0.27 \u0026plusmn; 0.45 \u0026ndash; 0.33 \u0026plusmn; 0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.4 (0.27 \u0026plusmn; 0.45- 0.33 \u0026plusmn; 0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerpentine Vessel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.47 (1.4 \u0026plusmn; 1.24 \u0026ndash; 1.87 \u0026plusmn; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.2 (1.4 \u0026plusmn; 1.24 \u0026ndash; 1.6 \u0026plusmn; 0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash; 3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.467 (1.87 \u0026plusmn; 0.99- 1.87 \u0026plusmn; 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eErythema\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Differences\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.867 (4.0- 3.13 \u0026plusmn;\u0026nbsp;0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e1.867 (4.0- 2.13 \u0026plusmn; 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e1 (3.13 \u0026plusmn;\u0026nbsp;0.6- 2.13 \u0026plusmn;\u0026nbsp;0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClod\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.6 (1.2 \u0026plusmn; 1.5 \u0026ndash; 0.6 \u0026plusmn; 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e1 (1.2 \u0026plusmn; 1.5 \u0026ndash; 0.2 \u0026plusmn; 0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.4 (0.6 \u0026plusmn; 1.1- 0.2 \u0026plusmn; 0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.247\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhite Structureless Areas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.267 (0.4 \u0026plusmn; 0.5 \u0026ndash; 0.67 \u0026plusmn; 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e1.467 (0.4 \u0026plusmn; 0.5 \u0026ndash; 0.87 \u0026plusmn; 1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSkin Coloured Structureless Area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Difference\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.533 (0.8 \u0026plusmn; 0.77 \u0026ndash; 1.33 \u0026plusmn; 1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e1.133 (0.8 \u0026plusmn; 0.77 \u0026ndash; 1.93 \u0026plusmn; 1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 42.1488%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40.6612%;\"\u003e\n \u003cp\u003e0.6 (1.33 \u0026plusmn; 1.29- 1.93 \u0026plusmn; 1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Repeated Measure ANOVA Test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Correlation analysis of variables\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"653\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month erythema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month erythema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDotted vessel at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month skin color structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month skin color structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month white structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month white structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale \u0026nbsp;0-1 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale \u0026nbsp;1-3 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0-3 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month erythema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month erythema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:0,232\u003c/p\u003e\n \u003cp\u003ep:0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDotted vessel at baseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:-0,555\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:-0,348\u003c/p\u003e\n \u003cp\u003ep:0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month skin color structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:-0,317\u003c/p\u003e\n \u003cp\u003ep:0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:-0,509\u003c/p\u003e\n \u003cp\u003ep:0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:0,319\u003c/p\u003e\n \u003cp\u003ep:0.247\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month skin color structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,187\u003c/p\u003e\n \u003cp\u003ep: 0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:-0,695\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:0,332\u003c/p\u003e\n \u003cp\u003ep:0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:0,917\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1st month white structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: 0,083\u003c/p\u003e\n \u003cp\u003ep:0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:0,444\u003c/p\u003e\n \u003cp\u003ep:0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,168\u003c/p\u003e\n \u003cp\u003ep:0,548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:0-,820\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:-0,898\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3rd month white structureless area\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: 0,113\u003c/p\u003e\n \u003cp\u003ep:0,687\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: 0,362\u003c/p\u003e\n \u003cp\u003ep:0.185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,132\u003c/p\u003e\n \u003cp\u003ep:0,639\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:-0,770\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:-0,843\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:0,977\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale 0-1 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,402\u003c/p\u003e\n \u003cp\u003ep:0,138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er: -0,552*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0,033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:0,652**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,367\u003c/p\u003e\n \u003cp\u003ep:0,179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,491\u003c/p\u003e\n \u003cp\u003ep:0,063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,301\u003c/p\u003e\n \u003cp\u003ep:0,276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,282\u003c/p\u003e\n \u003cp\u003ep:0,308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale 1-3 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,231\u003c/p\u003e\n \u003cp\u003ep:0,408\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er: -0,675**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0,006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er:0,143\u003c/p\u003e\n \u003cp\u003ep:0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,357\u003c/p\u003e\n \u003cp\u003ep:0,191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,448\u003c/p\u003e\n \u003cp\u003ep:0,094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,359\u003c/p\u003e\n \u003cp\u003ep:0,189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,326\u003c/p\u003e\n \u003cp\u003ep:0,236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003er: 0,367\u003c/p\u003e\n \u003cp\u003ep:0,179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Activity Scale 0-3 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003er: -0,477\u003c/p\u003e\n \u003cp\u003ep:0,072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er: -0,634**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0,011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.40979%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er:0,656**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,317\u003c/p\u003e\n \u003cp\u003ep:0,25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: 0,448\u003c/p\u003e\n \u003cp\u003ep:0,094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,331\u003c/p\u003e\n \u003cp\u003ep:0,228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.5505%;\"\u003e\n \u003cp\u003er: -0,293\u003c/p\u003e\n \u003cp\u003ep:0,290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er: 0,719**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0,003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u003cstrong\u003er: 0,663**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep:0,007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.33945%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePearson correlation analysis\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"448\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e**. Correlation is significant at the 0.01 level (2-tailed).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e*. Correlation is significant at the 0.05 level (2-tailed).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Visual Analog Scale\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisual Analogue Scale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.8017%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Differences\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0083%;\"\u003e\n \u003cp\u003e0\u0026ndash;1. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.8017%;\"\u003e\n \u003cp\u003e0.4 (1.13 \u0026plusmn;\u0026nbsp;0.35- 1.53 \u0026plusmn;\u0026nbsp;0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0083%;\"\u003e\n \u003cp\u003e0\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.8017%;\"\u003e\n \u003cp\u003e0.733 (1.13 \u0026plusmn;\u0026nbsp;0.35- 1.87 \u0026plusmn;\u0026nbsp;0.64)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39.0083%;\"\u003e\n \u003cp\u003e1\u0026ndash;3. month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.8017%;\"\u003e\n \u003cp\u003e0.34 (1.53 \u0026plusmn;\u0026nbsp;0.51- 1.87 \u0026plusmn;\u0026nbsp;0.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1901%;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Repeated Measures ANOVA Test\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5925739/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5925739/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eInfantile hemangiomas (IH) are the most common benign vascular tumors in infants, often requiring treatment in 10\u0026ndash;15% of cases due to complications. While systemic propranolol is the first-line treatment, its potential for systemic side effects raises interest in topical therapies. This study investigates the efficacy of topical 2% carteolol in treating IH and its dermoscopic changes over time.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 15 patients with IH were treated with topical 2% carteolol drops applied twice daily for 3 months. Clinical and dermoscopic images were captured at baseline, 1 month, and 3 months. Dermoscopic features such as erythema, clods, coiled vessels, dotted vessels, and others were evaluated. Visual Analog Scale (VAS) scores were used to assess treatment response.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe most frequent dermoscopic findings at baseline were coiled vessels, followed by serpentine and dotted vessels. At 1 and 3 months, significant improvements were observed, with reductions in erythema and coiled vessel scores (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and at 3 months with reductions in clod score (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The skin-colored structureless area significantly increased, indicating lesion regression (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). VAS scores showed a significant decrease over the 3-month period, with a positive correlation between baseline dotted vessel scores and treatment response (r:0.656, p:0.008).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eTopical 2% carteolol is an effective and safe treatment for IH. Dermoscopic monitoring provides valuable insights into treatment progression, showing significant changes in erythema, clod, and vascular patterns. The presence of dotted vessels at baseline may serve as a predictor of a favorable treatment response. Further studies with longer follow-up are needed to validate these findings.\u003c/p\u003e","manuscriptTitle":"Efficacy of Topical 2% Carteolol in the Treatment of Infantile Hemangiomas: A Dermoscopic and Clinical Evaluation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-04 08:55:43","doi":"10.21203/rs.3.rs-5925739/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-03-18T18:56:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35638151893812080094448320755798811317","date":"2025-03-18T18:40:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316103369496689706790859296297327592266","date":"2025-03-16T02:54:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"287824671360345168950390950134253116594","date":"2025-03-15T17:45:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-04T14:58:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-01-31T10:19:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-01-31T10:19:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2025-01-29T17:06:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"89a6a856-f465-49b1-9009-a896b2927893","owner":[],"postedDate":"February 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-03-21T22:23:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-04 08:55:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5925739","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5925739","identity":"rs-5925739","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}