Intralesional corticosteroid injections for infantile hemangioma

Infantile hemangiomas(IHs) are the most common benign soft-tissue tumors in infancy;about 10%–15% of them may result in various complications that require active management. The current first-line treatment for IH is oral propranolol;however, some studies recommend intralesional corticosteroid injections for small, limited, deep, or prominent tumors because of concern regarding serious systemic complications related to propranolol. This review summarizes and analyzes the current clinical studies on corticosteroid injections in IHs, discusses treatment norms, and explores future research directions.

Prenatal ultrasound diagnosis of congenital infantile fibrosarcoma and congenital hemangioma: Three case reports

BACKGROUND Congenital infantile fibrosarcoma(CIF)and congenital hemangioma(CH)have similarities on prenatal ultrasound and are rare.CASE SUMMARY We report 3 cases of fetuses with superficial hypervascular tumors,confirmed by postnatal pathology as CIF(1 case)and CH(2 cases,including 1 in a twin fetus).In Case 1,a mass with a rich blood supply in the fetal axilla was discovered by prenatal ultrasound at 28+0 wk of gestation.The postpartum pathological diagnosis was CIF,the mass was surgically removed,and the prognosis of the child was good.In Case 2,at 23+1 wk of gestation,a mass was discovered at the base of the fetus’s thigh on prenatal ultrasound.The postpartum pathological diagnosis was CH.After conservative treatment,the mass shrank significantly.Case 3 occurred in a twin fetus.At 30+0 wk of gestation,prenatal ultrasound revealed a bulging mass with a rich blood supply on the abdominal wall of one of the fetuses.Three weeks later,the affected fetus died,and the unaffected baby was successfully delivered by emergency cesarean section.The affected fetus was pathologically diagnosed with CH.CONCLUSION Prenatal ultrasound can provide accurate information,such as the location,size and blood supply of a surface mass in a fetus.We found similarities between CIF and CH in prenatal ultrasound findings.Although it is difficult to distinguish these conditions by prenatal ultrasound alone,for superficial hypervascular tumors that rapidly increase in size in a short period,close ultrasound monitoring of the fetus is required to quickly address possible adverse outcomes.

Cardiovascular drugs in the treatment of infantile hemangioma

Since the introduction of propranolol in the treatment of complicated infantile hemangiomas(IH) in 2008, other different beta-blockers, including timolol, acetabutolol, nadolol and atenolol, have been successfully used for the same purpose. Various hypotheses including vasoconstriction, inhibition of angiogenesis and the induction of apoptosis in proliferating endothelial cells have been advanced as the potential beta-blockerinduced effect on the accelerated IH involution, although the exact mechanism of action of beta-blockers remains unknown. This has generated an extraordinary interest in IH research and has led to the discovery of the role of the renin-angiotensin system(RAS) in the biology of IH, providing a plausible explanation for the beta-blocker induced effect on IH involution and the development of new potential indications for RAS drugs such as angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the treatment of IH. This review is focused on the current use of cardiovascular drugs in the treatment of IH.

Clinical Evaluation of Color Doppler Ultrasound in Selecting the Optimal Treatment Modality for Infantile Hemangioma

Objective We investigated the efficacy and safety of 1064 nm Nd： YAG laser, intense pulsed light （IPL）, and lauromacrogol injection in the treatment of hemangioma, in order to evaluate the value of color Doppler ultrasound guidance in choosing the optimal treatment modality. Methods Infantile patients who were clinical diagnosed as hemangiomas were randomly divided into group A, who had color Doppler ultrasound examinations before the treatment, and group B who had the treatment without ultrasound evaluation. Patients in the group A were assigned into subgroups according to the depth of lesion by sonography： group A-1 for those who had a lesion depth 〈1.2 mm, and took intense pulsed light therapy; group A-2 for those who had a lesion depth ≥1.2mm and 〈 3 mm, and took long pulse 1064 nm Nd：YAG laser therapy; group A-3 for those who had a lesion depth ≥3mm and 〈5 mm, and were treated by IPL combined with long pulse 1064 nm Nd：YAG laser treatment; Group A-4 for those who had a lesion depth ≥5 mm, and took lauromacrogol injection therapy. Patients in the group B took long pulse 1064 nm Nd：YAG laser treatment without preoperative ultrasound evaluation. The efficacy and adverse reactions of the treatments between the groups were evaluated and compared statistically. Results Totally 113 patients with 128 skin lesions were enrolled in this study, 85 in the group A （mean age 6.8±7.9 months） and 28 in the group B （mean age 6.9±9.9 months）. The mean depth of hemangioma was 3.3±1.1 mm in the group A, ranging from 0.5-7.8 mm, with 0.8±0.4 mm, 2.2±0.4 mm, 4.2±0.6 mm and 6.2±0.7 mm in group A1, A2, A3 and A4, respectively. The cure rates and effective rates in the group A were significantly higher than those in the group B （cure rates： 64.5% vs 56.3%, U=3.378, P=0.045; effective rates： 89.5% vs 78.1%, U=4.163, P=0.041）. The adverse effect rates of the group A （vesicle 20.0%, pigmentation 46.9%, scarring 17.7%） were lower than those of the group B （vesicle 21.9%, pigmentation 60.4%, scarring 25.0%）. Incidences of pigmentation and scarring were statistically significantly different （U=3.884, P=0.034, and U=4.016, P=0.032 respectively） between the two groups. Conclusion With the guidance of color Doppler ultrasound, the efficacy and safety of long pulse 1064 nmNd：YAG laser, intense pulsed light, and lauromacrogol injection in the treatment of infantile hemangioma have better outcomes compared to laser treatment alone without preoperative ultrasound examination.

Topical Propranolol Hydrochloride Gel for Superficial Infantile Hemangiomas

The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected to the topical propranolol hydrochloride gel intervention in Fuzhou General Hospital of Nanjing Military Commands, China. Changes in size, texture, color, peak systolic velocity of the hemangiomas, resistance index and adverse effects were observed. The results were evaluated by using Achauer system, and responses of IHs to pranpronolol were considered scaleⅠ(poor) in 4 patients (17.24%), scaleⅡ(moderate) in 18 patients (24.14%), scale Ⅲ (good) in 22 patients (44.83%) and scale Ⅳ (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P<0.05), and no differences in response were found among different primary sites (P>0.05). Our study indicates that topical application of 3% propranolol hydrochloride gel is effective and safe in treating IHs.

Clinical observations on the treatment of infantile hemangiomas with topical imiquimod 5% cream

Objective： To observe the efficacy and safety of topical imiquimod 5% cream in the treatment of uncomplicated infantile hemangiomas （IHs）. Methods： A total of 68 IHs were treated with topical imiquimod 5% cream. Among them, 36 were superficial, 22 were mixed, and 10 were deep. The size of IHs ranged from 1.0 cm × 1.5 cm to an area of a whole forearm. All the hemangiomas were in a proliferative stage. Imiquimod was applied 3 times weekly in 44 patients and 5 times weekly in 24 patients for up to 36 weeks. Results： All superficial IHs improved, and 18 achieved complete clinical resolution, 10 had excellent improvement, 5 showed moderate improvements, and 3 patients displayed minimal improvement. Two mixed IHs showed excellent improvement, 3 showed moderate improvement and 5 manifested minimal improvements. The remaining 12 mixed IHs and all deep IHs did not respond to the therapy. The total incidence of local adverse events was 58.82%（40/68）, which included erythema or edema, local itching, incrustation or peeling, erosion or ulceration, although most of these were mild to moderate reactions and did not affect the treatment. Scarring occurred in 2 mixed IHs. No systemic side effects developed. Conclusion： Imiquimod 5% cream may be a safe and effective alternative for the treatment of superficial IHs and some mixed IHs in which the superficial component predominates. An appropriate treatment duration for proliferative IHs treated with this therapy may be 24 weeks. Some local adverse events, such as crusting and erosion with possible scarfing potential may occur and should be addressed by prompt, but temporary, discontinuation of the imiquimod. Topical imiquimod 5% cream can be prudently used in the treatment of IHs larger than 5.0 cm × 5.0 cm in newborns and infants less than 6 months of age. To our knowledge, this is the largest IH group treated with imiquimod that has been reported in the literature to date.

Analysis of the therapeutic evolution in the management of airway infantile hemangioma

AIM: To analyze the evolution in the management of airway infantile hemangioma(AIH) and to report the results from 3 pediatric tertiary care institutions.METHODS: A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed. RESULTS: Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo(range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases(no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients(in 5 of them as a single treatment) with a response rateof 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients(in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo(range, 5-10); complications were not observed. CONCLUSION: Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH.

Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review

BACKGROUND We have previously proved that treatment of thick/deep infantile hemangiomas (IHs) with a long-pulse Alexandrite laser was clinically effective and safe. This article aims to investigate the efficiency of long-pulse Alexandrite laser use in treating thick and high-risk IHs located in particular anatomic areas and provides some new data on this issue. CASE SUMMARY A two-month-old girl with a thick and high-risk IH covering most of the right labia majora was examined in this study. The infant received four treatment sessions at 4- to 6-wk intervals with a long-pulse Alexandrite laser with settings as follows: 3 ms pulse duration, 8 mm spot size, 45 to 50 J/cm2 fluences, and dynamic cooling device (DCD) spray duration of 90 ms with a delay of 80 ms. Following each of the four treatment sessions, the IH showed a remarkable reduction in thickness and size without any sign of relapse. Ten months after the last treatment, the IH had completely regressed without adverse effects. During the laser treatment, no severe side effects were observed;blistering occurred only immediately after treatment and then scabbed over the next day, gradually improving in the following days. CONCLUSION Long-pulse Alexandrite laser treatment may be considered one of the first-line noninvasive therapeutic options for the treatment of thick IH.

The apoptosis in various stages of infantile hemangioma

Objective: To detect the apoptosis in various stages of infantile hemangioma. Methods:Total 52 samples of infantile hemangioma (including 8 fresh samples) were included in this study. Agarose gel electrophoresis, transmission electron microscopy(TEM) and in situ TdT mediated dUTP-biotin nick end labeling(TUNEL) staining were used to observe the apoptosis. H-E staining was used to analyze the number of cells,the number and area of microvessels in hemangiomas. Results: The typical “ladder” occurred in the DNA electrophoresis of the hemangioma tissue in the late proferating stage. Many apoptotic cells were found in infantile hemangiomas with TEM. TUNEL staining identified that there were apoptotic cells througout the pathologic evolution of infantile hemangioma and the AI(%) was the highest in the late proferating stage. There existed close relationship between the AI(%) and the total number of cells in hemangioma. Conclusion: The decrease of cells resulted from the apoptosis may be the major cause of the spontaneous involution of infantile hemangioma.

Dermoscopic Appearances in the Superficial and Deep Type of Infantile Hemangioma

Infantile hemangioma is clinically classified as superficial, superficial and deep (mixed), and deep. Dermoscopy can be used for analyzing vascular structure and for classifying infantile hemangioma. Here, we focus on vascular features of the superficial and deep type of infantile hemangioma and show the three characteristic dermoscopic forms, mostly reddish, diffuse reddish, and cerebriform reddish.

Propranolol for infantile hemangioma: Current state of affairs

Infantile hemangioma(IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating on associated anomalies, such as PHACE(S) syndrome and LUMBAR syndrome. Because of the benign and self-limiting characteristics seen in more than 90% of cases of IH, a conservative approach is usually chosen. However, some circumstances, such as ulceration, vision loss, breathing difficulties, or potential disfigurement, will require treatment during the proliferative phase. For decades, treatment of IH has primarily consisted of corticosteroids or surgery. Since 2008, propranolol has become the treatment of first choice. In this article, we bring to light the crucial changes in the treatment of IH over the past years. To date, there is still a lack of data on the possible long-term effects of propranolol treatment in young infants. A theoretical probability of the central nervous system being affected(that is, impairment of short- and long-term memory, psychomotor function, sleep quality, and mood) has recently been suggested. This review highlights research topics concerning these long-term adverse effects. Finally, information is provided on the potential instruments to measure IH severity and activity in clinical trials and/or in clinical practice and the recently developed and first-validated IH-specific quality-of-life questionnaire.

Vectra 3D Imaging for Quantitative Volumetric Analysis of the Efficacy of Propranolol in Infantile Hemangioma

Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the effectiveness of oral propranolol administration, we measured quantitative changes in an IH by digital camera and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Although digital cameras are very simple, changes in color tones occur with time, lesions are evaluated in two dimensions, and changes in the thickness of the hemangioma are difficult to evaluate. Therefore, we investigated the feasibility of 3D photography to quantify volumes in IH during oral propranolol treatment.

Differentiation and Pro-Angiogenic Potential of Infantile Hemangioma Stem Cells

Objectives Infantile hemangioma(IH)is defined as a benign vascular tumor composed of immature vascular endothelial cells,with the unique characteristics of rich vascularization and self-regression into fibro-fatty tissue.CD133-positive hemangioma stem cells(HemSCs),present in the proliferating IH tissue,can be used to establish the IH animal model,which has highlighted the pathogenesis of IH in recent years.This study focused on the biological characteristics and differentiation capacity of HemSCs and aimed to provide a theoretical possibility for its application in tissue engineering.Methods To further confirm our hypothesis,we used fluorescence-activated cell sorting(FACS),in vitro multipotent induced differentiation,angiogenesis assay,and antibody array to identify the surface markers,multipotent differential potential,angiogenesis potential,and secreted factors of HemSCs,respectively,utilizing human adipose stem cells(hADSCs)as the control.Results We successfully isolated and cultured HemSCs.FACS indicated that,on average,more than 80%of HemSCs matched the criteria of mesenchymal stem cell(MSC)surface markers.Our results confirmed that HemSCs could differentiate into adipocytes,osteocytes,and chondrocytes.Additionally,compared with fibroblasts or hADSCs,HemSCs could promote angiogenesis through para-secretion.Conclusions HemSCs may originate from normal MSCs,and owing to their powerful proliferative and angiogenic abilities,they could be considered an IH pathogenic factor.These characteristics demonstratet heir potential as a candidate seed cell in tissue engineering.

Oral Propranolol: A Useful Treatment for Infantile Hemangioma

Background: Infantile haemangioma is the commonest childhood tumor. Several lines of treatment are available. Recent reports have focused on the value of propranolol in treating rapidly proliferating haemangioma. The aim of this study was to assess oral propranolol in treatment for facial haemangioma. Patients and Methods: Fifteen patients with rapidly proliferating infantile facial haemangioma with cosmetic disfigurement were treated with oral propranolol. All patients had cardiovascular pre-treatment work-up and commenced on oral propranolol at 3 mg/kg/day. Results: A rapid decrease in hemangioma proliferation was seen in 100% of patients and significant regressions occuring in all patients. This treatment was well tolerated and had little side effects. Conclusions: Oral propranolol is a reliable and easily reproducible method for treatment of facial hemangioma.

Burn Hemangioma (BH) (Scalded Pyogenic Granuloma) versus Infantile Hemangioma: Report of Six Cases of BH and Its Effective Therapy with Oral Propranolol

Infantile hemangioma and burn hemangioma have many similarities in clinical pictures, pathology and treatment. As infantile hemangioma appears usually after birth and then rapidly grow within few months and then a statue state and then involutes within few years while burn hemangioma so called burn pyogenic granuloma usually appears within days after burn with liquid and grow rapidly into many giant angiomatous masses and then after short time usually weeks or months will involute in more than 37.5% of cases. Hence burn hemangioma and infantile hemangioma sharing many similar features as both are angiomatous with dramatic rapid proliferation of blood vessels that followed by involution but with different time periods and both carry CD133 and CD34 for infantile hemangioma and CD34 for burn hemangioma. Also infantile hemangioma rapidly responds to systemic propranolol and similarly do in cases of burn hemangioma. Accordingly it is more better scientifically to call scalded pyogenic granuloma burn hemangioma. The objective of the present report is to review these conditions and do comparison between them and also to record 6 cases of burn hemangioma and its effective therapy with oral propranolol.

Early Pulsed Dye Laser Treatment for Infantile Hemangiomas: An Open Study for 50 Japanese Infancies

Infantile hemangiomas, occurring at birth or during the first weeks of life, are benign vascular tumors with an initial proliferative phase and a later involutional phase. The massive proliferation on the key regions and unpredicted regression may threaten?life. Thus, early management of infantile hemangiomas is necessary for affected infancies. Recent studies showed that propranolol for infantile hemangiomas had high efficacy for disappearance or reduction of infantile hemangiomas. However, a most recent study demonstrated existence of propranolol-resistant infantile hemangiomas. Therefore, we retrospectively evaluated efficacy of established early pulsed dye laser treatment for infantile hemangiomas in the 50 Japanese infancies which were applied in the period from 2000 to 2005, because our series included from the plaque subtype to the more proliferative tumor subtype. High efficacy in both subtypes suggests that early pulsed dye laser treatment can still be included as the first option for the mixed type of infantile hemangiomas and that pulsed dye laser treatment may be useful as the second line for the propranolol-resistant mixed type of infantile hemangiomas.

Stem cells in infantile hemangioma

Background:Infantile hemangioma(IH)is the most common tumor of infancy and the pathogenesis is still unclear.Recent new evidences have been shown that IH arises from stem cells.Data sources:Based on recent original publications from Pub Med,Elsevier and Google Scholar,a large number of articles about pathogenesis and treatment of IH were selected by their titles and abstracts.Results:The hemangioma-derived stem cells expressed stem cell-specific marker CD133 and mesenchymal markers CD29,CD44,and comprised between 0.1%and 1%of the cells in proliferating-phase IH.During the proliferative phase,stem cells differentiated into large amounts of endothelial cells and pericytes;while during the involuting phase,stem cells became less and predominantly differentiated toward adipocytes.Signaling pathways like VEGF/VEGFR,Notch signaling,were found to be related to these processes.Corticosteroids,Rapamycin and propranolol had a significant effect on stem cells by inhibiting the cell growth or differentiation,or participating in maintaining the cell stability.Conclusions:Stem cells derived from hemangioma play an important role in the pathogenesis of IH,and may be important targets of therapy.

Distribution and pheotype changes of macrophage in infantile hemangioma

Objective To observe distribution and phenotypc changes of macrophage in infantile hemangioma. Methods Forty - three infantile hemangioma samples were harvested from resection operation,Distribution and phenolype changes of macrophages labelled with CD68,

Infantile hemangiomas screening modalities for primary care physicians

Infantile hemangiomas are the most common benign vascular tumors in children.They present a characteristic natural history of spontaneous involution after a phase of initial proliferation.A small but significant minority demonstrates incomplete regression or complications and requires prompt intervention.Prediction of the evolution of infantile hemangiomas is challenging because of their morphological and behavioral heterogeneity.The decision between referral for treatment and observation is sometimes difficult,especially among non-expert physicians,with the risk of missing the period for optimizing outcomes in case of delayed intervention.The aim of this review is to update our knowledge,especially of the primary care providers,regarding the ongoing difficulties of the early clinical evaluation of infantile hemangiomas,and to outline the importance of current practical scoring tools for the identification of the lesions which require expert consultation and referral.

Risk factors for infantile hemangioma:a meta-analysis

Background Infantile hemangioma(IH)is one of the most common tumors in infants.Its pathogenesis is complex and poorly understood.The risk factors of IH have been extensively studied from clinical and epidemiological perspectives in recent years,but the conclusions in the literature reports are inconsistent.To provide a reference for the prevention of hemangioma,we conducted a meta-analysis of the published studies of potential risk factors for IH.Methods The Cochrane Library,Ovid,PubMed,and Web of Science databases were searched systematically.Log odds ratios(log ORs),logistic regression standard errors and 95%confidence intervals(CIs)were used to compare the correlation between IH and potential risk factors.Review Manager 5.3.3 was used for the statistical analysis.Results Six studies were included and 17 potential risk factors were eventually evaluated.P values<0.05 were found for female gender(P<0.01,OR 2.04,95%CI 1.65–2.51),low birth weight(P<0.01,OR 4.39,95%CI 3.05–6.31),multiple gestation(P=0.01,OR 2.39,95%CI 1.21–4.71),preterm birth(P=0.03,OR 2.37,95%CI 1.07–5.23),progesterone therapy(P<0.01,OR 2.73,95%CI 2.12–3.51),and family history(P=0.01,OR 1.98,95%CI 1.16–3.38).Conclusions This meta-analysis revealed that risk factors,including female gender,low birth weight,multiple gestation,preterm birth,progesterone therapy,and family history may affect the occurrence of IH.