Superficial Infantile Hemangiomas Research Articles

A retrospective multicenter cohort study of differences in clinical characteristics of Infantile Hemangiomas in preterm and term infants: Prematurity increases risk of permanent cutaneous sequelae

BackgroundWe observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with increased risk of scarring. ObjectiveTo compare the clinical features of localized IH in preterm versus term infants. MethodsA retrospective study at three tertiary referral centers was conducted on 830 consecutive patients with localized IH. ResultsPreterm infants had a significantly higher incidence of superficial IH (75% in <33weeks, 57% in 33-<37 weeks, and 50% in term infants, p=0.007). Overall, their IH had thicker superficial components (p<0.001) and more stepped borders (p<0.001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD=6.2) months, with no difference between gestational age. LimitationsThe retrospective design and use of non-standardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers. ConclusionPreterm infants have features of IH that have obvious implication for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred.

Serum apelin as a potential biomarker for infantile hemangiomas.

Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas.

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective β-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.

Timing and Efficacy Evaluation of 755-nm Long Pulse Alexandrite Laser and 2% Carteolol Hydrochloride Eye Drops Co-Treatment for Thicker Superficial Infantile Hemangioma.

Superficial Infantile hemangioma (SIH) is the most common type of IH. Some studies have shown the efficacy of 755-nm long pulse alexandrite laser (LPAL) and topical 2% carteolol hydrochloride (C-HCL) eye drops for the treatment of SIH. This article retrospectively analyzes the safety and efficacy of 755-nm LPAL combined with 2% C-HCL eye drops for treating thicker SIH, and explores the optimal treatment time for SIH. This study included 2-5 mm thick SIH patients who received co-treatment of 755-nm LPAL and 2% C-HCL eye drops. The SIH patients were divided into 3 groups based on their age and IH growth curve: ≤ 1 month (≤ 1M), 1-3 months (excluding 1 month; 1-3M), and 3-12 months (excluding 3 months; 3-12M). There was no difference in efficacy between the ≤ 1M and the 1-3M group, and were both better than the 3-12M group. Furthermore, there was no difference in the average number of treatments between the ≤ 1M and 1-3M groups and were both less than the 3-12M group. There was no significant difference in the incidence of adverse reactions between the groups. Compared with the ≤ 1M and 1-3M groups, the 3-12M group indicated more permanent skin lesions after the treatment. It was revealed that co-treatment with 755-nm LPAL and 2% C-HCL eye drops is safe and effective against thicker SIH. Compared with the 3-12M group, ≤ 3 months can achieve better efficacy, requires a shorter treatment time, less likely to leave permanent skin lesions such as scars. Moreover, patients with no proliferation can be observed to 1 month.

O07 Faceless PHACES

Abstract PHACES syndrome (posterior fossa – haemangioma – arterial – cardiac – eye – sternal) is a multisystem disorder which often presents first with a facial, segmental infantile haemangioma (IH). Prompt recognition of this subtype of IH is key to enable early detection of neurological/ophthalmological/cardiac anomalies. As per international consensus guidelines, the presence of a facial segmental haemangioma &amp;gt; 5 cm triggers screening for associated extracutaneous anomalies. We present three infants with absent/minimal facial haemangioma, but who fulfilled extracutaneous criteria of PHACES syndrome. Patient 1 was a 3-week-old female who presented with a 1–2-cm linear superficial left post-auricular IH. PHACES screening revealed an atrial septal defect, intracranial haemangiomas and hypoplastic cerebrovasculature. Patient 2, a 9-month-old girl, was admitted to intensive care following acute respiratory deterioration. Examination revealed a segmental IH of the occipital scalp. PHACES screening revealed a vascular ring, right aortic arch, aberrant subclavian artery, subglottic and mediastinal IH and narrowing/tortuosity of the left internal carotid artery. Patient 3, a 4-month-old male, was referred for evaluation of three superficial IH, all &amp;lt; 0.5 cm, one on the right post-auricular skin and two on the right forehead. He suffered acute collapse at 2 weeks of life leading to a diagnosis of obstructed total anomalous pulmonary–venous connection requiring emergency surgical correction. PHACES screening revealed bilateral dysplastic/torturous internal carotid arteries. We present three cases of PHACES syndrome without the classic facial segmental IH. Clinicians should be aware of the spectrum of IH observed in PHACES syndrome to enable prompt screening of those presenting with atypical scalp and post-auricular lesions.

Topical Application of 0.5% Timolol Maleate Hydrogel for the Treatment of Superficial Infantile Hemangiomas.

Oral propranolol is considered the first line therapy in the treatment of infantile hemangiomas (IHs). However, there are considerable side effects due to its ability to penetrate the blood brain barrier. Alternatively, topical timolol, a non-selective beta blocker, has resulted in fewer side effects and is 4&ndash;10 times more potent in comparison to oral propranolol. This study evaluates the efficacy of 0.5% timolol maleate hydrogel for the treatment of IH. This study was conducted via a quasi-experimental design from October 30, 2020 &ndash; April 29, 2021, at the Department of Dermatology Benazir Bhutto Hospital, Rawalpindi. 145 infants between 1&ndash;12 months in age diagnosed with superficial cutaneous hemangiomas were included in the study with a male to female ratio of 2.4:1. A thin layer of timolol maleate 0.5% hydrogel was applied to the entire surface of the patient&rsquo;s IH three times daily. Digital photographs and measurements of the hemangiomas were taken at one-month intervals for a maximum of 6 months. The age range in this study was from 1&ndash;12 months with a mean age of 6.10 &plusmn; 2.52 months. The majority of the patients 89 (61.4%) were between 1&ndash;6 months of age. Of the 145 patients, 89 (61.4%) showed an excellent response, 44 (30.3%) showed a good response, and 12 (8.3%) showed no response to the topical 0.5% timolol maleate hydrogel treatment. The use of topical 0.5% timolol maleate hydrogel is a promising therapeutic option for the treatment of superficial IHs. Anwar F, Mahmood E, Sharif S, et al. Topical application of 0.5% timolol maleate hydrogel for the treatment of superficial infantile hemangiomas. J Drugs Dermatol. 2023;22(6):594-598. doi:10.36849/JDD.7054.

Development of a digital imaging analysis system to evaluate the treatment response in superficial infantile hemangiomas.

Superficial infantile hemangiomas (IH) are benign vascular tumors common in children characterized by bright red "strawberry" lesions on the skin. In order to optimize the treatment for this disease, there is a need to develop objective tools to assess treatment response. Since a color change in the lesion is a good indicator of treatment response, we have developed a digital imaging system to quantify the values of red, green, and blue (RGB) difference and RGB ratio between the tumor and normal tissue to take into account the variations in color between different skin types. The efficacy of the proposed system in assessing treatment response in superficial IH was evaluated in relation to established visual and biochemical tools used to grade hemangiomas. As the treatment progressed, the RGB ratio was almost 1, while the RGB difference was close to 0, which indicates a good response to treatment. There was a strong correlation between the RGB score and the other visual grading systems. However, the correlation between the RGB scoring system and the biochemical method was weak. These findings suggest that the system can be used clinically to objectively and accurately evaluate disease progression and treatment response in patients diagnosed with superficial IH.

Intralesional steroid in the era of propranolol for infantile hemangioma—Do we need it?

Despite its effectivity, there are reports of poor response to propranolol in the treatment of infantile hemangioma (IH). The literature is limited to the type of IH that fails to respond to propranolol. This study was conducted to analyze which types of hemangiomas respond poorly to propranolol and the effects of intralesional triamcinolone (IL TMC) in them. In this prospective cohort study, IH was classified as superficial, deep, and mixed. The clinical details were recorded. Propranolol was started in the patients at a dose of 1mg/kg/day and increased to 2-3mg/kg/day. The response to the treatment was evaluated as excellent, good, poor, and no response. IL TMC was given in the non-responding group at a dose of 1-2mg/kg at one-month interval for a total of six doses after stopping propranolol. Ninety-six patients (median age, 7 months; M/F=2:1) were treated. Superficial hemangioma was present in 40 (41.7%), deep in 10 (10.4%), and mixed in 46 (47.9%) patients. The response was statistically better if initiated within four months of age. It was not influenced by the sex, number, site, or size. The response was statistically better in superficial hemangioma. IL TMC was administered in the 16 patients. The response was good or excellent in 10 patients. Propranolol will be used as a first-line drug for IH. All superficial IHs are likely to respond. There will be a possibility of non-responding mixed or deep IH. Use of IL TMC seems reasonable for IH not responding to propranolol.

Predictors of treatment responses of superficial infantile hemangiomas to topical timolol.

Topical timolol is not effective in the treatment of some superficial infantile hemangiomas (IHs). This is a prospective study aiming to investigate the predictors of treatment response of superficial IHs to topical timolol. Patients with superficial IHs were prescribed timolol 0.5% cream four times daily and followed up every 2-3months until 1 year of age. IH thickness was objectively measured by ultrasound, and the proportional change was calculated as a regression rate. In total, 193 patients (211 lesions) were enrolled. Topical timolol was initiated at an average age of 3.1 (0-6) months for 7.4 (2-11) months. The average regression rate of all lesions was 41.8% (-137.5%-100%). Lesion thickness (p=0.000) and patient age at initial treatment (p=0.001) were major variables that predicted the treatment response. On average, an increase in lesion thickness of 1 mm decreased the regression rate by 22.1%, and lesions thicker than 1.9 mm were unlikely to respond (average regression rate=-0.27%). Available results did not show a significant effect of sex (p=0.659), lesion size (p=0.311), or location (p > 0.05) on regression. Treatment for superficial IHs should be individualized according to lesion thickness and patient age.

33425 Topical timolol treatment for superficial infantile hemangiomas: Therapeutic response according to clinical subtypes

Background: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. Topical timolol, a nonselective beta-blocker, has been used for IHs as a safe and effective management option. However, few studies have evaluated the response of topical timolol according to the clinical subtypes of IHs.

Efficacy and safety of propranolol cream in infantile hemangioma: A prospective pilot study

Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35–150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1–85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.

An exploration of optimal time and safety of 595-nm pulsed dye laser for the treatment of early superficial infantile hemangioma.

Infantile hemangioma (IH) is the most common benign vascular tumor that occurs in infants and young children. Studies have shown laser therapy to reduce the proliferation of superficial IH and promote its regression, but the optimal timing for treatment has not been determined. Our study explores the timing and safety of 595‐nm pulsed dye laser (PDL) treatment for early superficial IH. We retrospectively analyzed 180 cases of superficial IH treated with 595‐nm PDL. Data was organized according to patient age at the first visit. Six months after the initial treatment, patients were evaluated using a grade IV classification method, and the clinical curative effect of each group was calculated. The number of laser treatments and the occurrence of adverse reactions were recorded simultaneously. The overall effective and cure rates were 98.3% and 84.4%, respectively, with no significant difference in rates between groups (p > 0.05). There was a statistically significant difference in the number of laser treatments among the age groups (p < 0.05). The average laser frequency: “0–2 months group” < “2–4 months group” < “4–6 months group.” The overall incidence of adverse reactions was 11.1%, and 12 (6.7%) cases had short‐term adverse reactions, with no statistically significant differences between groups (p > 0.05). Eight cases had long‐term adverse reactions. This difference between groups was statistically significant (p < 0.05). Younger children (≤2 months of age) receiving 595‐nm PDL treatment for IH require relatively fewer treatment times than other children (>2 months of age), have a shorter course of disease, experience better curative effect, and have fewer sequelae reactions.

Application of topical betaxolol for curing superficial infantile hemangioma: A pilot study.

Beta-blockers have gradually become an attractive option for the treatment of infantile hemangiomas. Topical application is more preferred over oral administration since their potential systemic adverse effects. The aim of this study is to investigate the effect of betaxolol in treating superficial infantile hemangioma. 74 infants admitted to the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2019 were observed and recorded. The changeable indicators such as color, size, tension and thickness were monthly recorded and evaluated according to visual analog scales. Multi-factor analysis of variance with repeated measurements and Kruskal-Wallis H nonparametric test were performed to compare the clinical effectiveness across different groups. After six months of treatment, 33.78% (25/74) got excellent results, 55.41% (41/74) had good response, 8.11% (6/74) had moderate response and 2.70% (2/74) had poor response respectively. Neither local discomforts nor systemic complications had been found. There was no significant difference in gender and location of occurrence among groups (P > 0.05), while the effect of topical application of betaxolol was optimum in the children aged 0-3 months (P = 0.002). None of three age groups had statistically significant discrepancy of heart rate and blood pressure after accepting treatment (one month, P = 0.618; four months, P = 0.138; six months, P = 0.757). Our study showed that topical administration of betaxolol was effective and well-tolerated for superficial infantile hemangiomas, particularly in the early proliferative stage. However, its safety and efficacy need continuous studies to be confirmed.

Good Clinical Responders to Topical Timolol in Patients with Infantile Hemangiomas: A 7-Year Retrospective Study of 328 Korean Patients.

BackgroundTopical timolol is widely used for treatment of superficial infantile hemangioma (IH). However, little is known about factors that affect the response to topical timolol treatment.ObjectiveThis study aimed to investigate the efficacy, safety, and predictive value for good response to topical timolol for IH.MethodsA retrospective review of medical records and clinical photos of 328 patients with IH treated with topical timolol 0.5% solution was conducted. Serial clinical photographs were compared with those at the initial visit using a 100-mm visual analogue scale (VAS). Treatment response was defined as an improvement of at least 75% from baseline in IH lesions within 12 months of treatment.ResultsOverall, IH patients treated with topical timolol showed significant improvement from baseline, showing that the final VAS score within 12 months of treatment was 69.7±20.4. The multivariable logistic regression analysis showed age at initiation of treatment (p=0.007), length of gestation and fetal growth (p=0.03), depth (p=0.01), and flexural area (p=0.007) were significantly associated with treatment response. Only four patients (1.1%) reported local irritation.ConclusionThis study demonstrated that topical timolol treatment was an effective and well-tolerated treatment for IHs. Physicians are encouraged to consider several patient- or lesional factors that might affect treatment response to achieve better clinical outcomes.

Results of Infantile Hemangioma Laser Therapy in Children with Persistent Residual Signs after Systemic Propranolol Therapy: Clinical Cases

Background. Infantile hemangiomas are revealed in 1-3% of newborns and 10-12% of infants. There are only anecdotal reports on the laser therapy efficacy in this pathology management. However, there is no common approach to the use of this method in the complex treatment of infantile hemangioma in infants. Clinical Cases Description. Two clinical cases of infantile hemangioma are presented. Patients underwent complex treatment: systemic propranolol and laser therapy via pulsed dye laser. Laser exposure modes ware selected individually: laser spot sizes were 10 and 12 mm, energy levels were 5-10 J/cm2, burst duration was short (0.45 ms) or long (10-20 ms), procedure duration was from 15 to 40 minutes, number of procedures varied from 1 to 8. Laser therapy has shown its efficacy in treatment of superficial infantile hemangioma. Conclusion. The indication for using laser therapy in management of infants with hemangiomas is especially persistent residual signs such as telangiectasias and erythema after spontaneous or drug involution phase. Laser therapy allows us to avoid aggressive methods and improves the quality of life of our patients according to this article.

Timing and Efficacy of 595-nm Pulsed-Dye Laser Combined with 0.5% Timolol Maleate Solution in the Treatment of Superficial Infantile Hemangiomas.

PurposeInfantile hemangioma (IH) is the most common benign tumor in infancy, and superficial IH is the most common type. IH can reportedly resolve spontaneously, but this is associated with complications, such as scars, atrophy, hypopigmentation, telangiectasia, and skin sagging, in 70% of cases. This study explores the safety and feasibility of therapeutic intervention with the 595-nm pulsed-dye laser (PDL) combined with 0.5% timolol maleate solution in superficial IH and compares the difference in efficacy between the early group and the late group.Patients and MethodsThis retrospective study examined 167 patients with superficial IH who underwent combination therapy at the Dermatology Clinic of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University between July 2019 and July 2020. The early and late groups were composed of children aged ≤2 and >2 months, respectively. Treatment was administered for 6 months, and patients were followed up for another 6 months. Two independent, double-blinded physicians reviewed photographs of the skin lesions before and after treatment to evaluate efficacy.ResultsThe early group demonstrated higher treatment efficacy than the late group. The early (n = 45) and late (n = 122) groups had treatment efficacy rates of 95.5% and 86.1%, respectively; the difference was statistically significant (P< 0.05). The early and late groups underwent 3.51 ± 0.50 and 4.73 ± 0.68 months of treatment, respectively; the difference was statistically significant (P< 0.05). Seventeen (44.4%) patients in the early group had immediate adverse reactions but no permanent sequelae, whereas 25 (20.49%) and 13 (10.7%) patients in the late group had immediate and permanent sequelae, respectively. The difference was statistically significant (P<0.05).ConclusionThis retrospective study demonstrated that 595-nm PDL combined with 0.5% timolol maleate solution was a safe and effective local treatment for superficial IH. Early treatment required fewer treatments, had better curative effects, and a lower probability of permanent sequelae.

Periorbital Mass in a 2-month-old Girl.

Periorbital Mass in a 2-month-old Girl.

Analysis of onset and clinical characteristics in Japanese patients with infantile hemangioma.

Infantile hemangioma (IH) is a common benign tumor during infancy, although the detailed mechanism behind it has not been fully elucidated. Based on previous studies, we hypothesized that formation of hemangioma might be triggered by secondary physiological events (perinatal hypoxia or mechanical stress during delivery) in patients carrying germline risk mutations. We aimed to clarify the mechanism by evaluating whether head and neck lesions were more frequent in patients in who IH appeared after birth compared with those in who it was present at birth. Clinical data of 62 lesions in 51 patients with IH were collected. All patients were analyzed for correlation of onset with gender, localization, family histories, gestational age, birth weight, and clinical subtypes. Distribution of lesions on the head and neck was slightly more frequent in the after-birth IH group, compared with those with IH present at birth, but without significant difference (47.6% vs. 40.0%, p = 0.32). On the other hand, the ratio of superficial and deep type IH at birth was significantly altered compared with that in IH after birth (19:0 vs. 26:7, p = 0.039). In addition, IHs appearing after birth tended to more commonly have multiple lesions than those with IH present at birth, with statistically significant difference (25.8% vs. 0%, p = 0.0164). There may therefore be different triggers for IHs at birth and IH after birth. Further studies with greater number of patients are necessary to validate these findings.

Update on infantile hemangioma.

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%–10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2–3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1–2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

Topical Timolol Combined Intralesional Injection of Diprospan in the Treatment of Elevated Localized Mixed Infantile Hemangiomas and a Discussion for Proper Timing for Injection.

Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ± 1.50 months (range: 1.00-6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.