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      Propranolol therapy for infantile hemangioma: our experience

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          Abstract

          Objective

          Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial proliferation and resolve without consequence, intervention is required in a subset of IHs, which develop complications resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment for this subset of IHs is pharmacological intervention, and propranolol has become the new first-line treatment for complicated hemangiomas. Here, we evaluated the efficacy of propranolol on proliferation IH in a clinical cohort including 578 patients.

          Methods

          We retrospectively reviewed a total of 578 IH patients who were treated with oral propranolol from January 2010 to December 2012. Responses to the propranolol treatment were graded as: excellent, good, poor, or no response. Based on the response to propranolol treatment (once daily at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily total dose of 2 mg/kg for patients older than 2 months), additional pharmacotherapies or surgery were used for IH patients for satisfactory clinical outcome.

          Results

          Five hundred and sixty (96.9%) of 578 IH patients in our study responded to oral propranolol treatment, and the response rate was significantly different for different ages of patients ( P<0.05), with the youngest patients having the highest response rate. The mean time of treatment was 6 months (range, 3–12 months). For example, response rate to propranolol was 98.1% in patients younger than 2 months, compared with 93.3% in patients older than 2 months and younger than 8 months, and 73.7% in patients older than 8 months. One hundred and thirty one patients who exhibited incompletely involuted hemangiomas were further treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and seventeen (89.3%) of 131 patients showed a positive response. There were no instances of life-threatening complications after propranolol. However, minor side effects were observed including 10 (1.73%) cases of sleep disturbance, 7 (1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm.

          Conclusion

          IH requires early intervention. During the involution phase, tapering propranolol dosage can be done to minimize side effects before discontinuing treatment. For patients exhibiting telangiectasia and chromatosis after propranolol treatment, administration of a 0.5% solution of timolol maleate or pulse dye laser is an effective therapeutic approach for complete involution.

          Most cited references24

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          Interferon alfa-2a therapy for life-threatening hemangiomas of infancy.

          Most hemangiomas are small, harmless birthmarks that appear soon after birth, proliferate for 8 to 18 months, and then slowly regress over the next 5 to 8 years, leaving normal or slightly blemished skin. In rare cases, hemangiomas can endanger vital structures, with a mortality of up to 60 percent. About a third of these life-threatening hemangiomas respond to treatment with corticosteroids, but for the others there is no safe and effective treatment. We evaluated the effects of daily subcutaneous injections of interferon alfa-2a (up to 3 million units per square meter of body-surface area) in 20 neonates and infants with life-threatening or vision-threatening hemangiomas that failed to respond to corticosteroid therapy. In 18 of the 20 patients the hemangiomas regressed by 50 percent or more after an average of 7.8 months of treatment (range, 2 to 13). One infant died of refractory proliferation of a lesion and consumptive coagulopathy. The condition of three other patients who had large hemangiomas associated with consumptive coagulopathies that were unresponsive to conventional therapies stabilized after seven days of treatment with interferon alfa-2a alone. Transient side effects of treatment with interferon alfa-2a included fever, neutropenia (one patient), and skin necrosis (one patient). No long-term toxicity has been observed after a mean follow-up of 16 months. Interferon alfa-2a appears to induce the early regression of life-threatening corticosteroid-resistant hemangiomas of infancy.
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            Current management of hemangiomas and vascular malformations.

            This article outlines the classification of vascular anomalies, which include vascular tumors and vascular malformations. We describe the nomenclature, diagnosis, and management of the different types of anomalies. Specific indications for pharmacologic and surgical intervention are discussed.
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              Beta blockade induces apoptosis in cultured capillary endothelial cells.

              Continuous beta blockade stimulates deposition of collagen in the pulmonary alveolar interstitium of adult rats. It also causes changes to the capillary endothelial cell compartment reminiscent of programmed cell death. To test whether beta blockade results in endothelial cell apoptosis, cultures of capillary endothelial cells were treated with both a wide-spectrum beta blocker and a beta-2-specific antagonist. Apoptosis was measured in these cultures using both terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling and annexin-V assays. Both forms of beta blockade stimulated programmed cell death in these cultures. To test whether the apoptotic effect of beta blockade was related to interstitial collagen deposition, capillary endothelial cells were cocultured with beta-blocked pulmonary fibroblast monolayers. Cocultured endothelial cells were substantially protected from apoptosis after beta blockade; coculture over plain tissue culture plastic or over exogenous collagen films had no effect on programmed cell death in endothelial cells. These results suggest that both pulmonary endothelial and interstitial cells are vulnerable to injury from beta blockade but that paracrine interactions between these cells may protect the peripheral lung from substantive damage.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                08 May 2017
                : 11
                : 1401-1408
                Affiliations
                [1 ]Department of Oral-Maxillary Head and Neck, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai
                [2 ]School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Jia-Wei Zheng, Department of Oral-Maxillary Head and Neck, Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, People’s Republic of China, Tel +86 21 2327 1063, Fax +86 21 6312 1780, Email zhjw@ 123456omschina.org.cn
                Weien Yuan, School of Pharmacy, Shanghai Jiao Tong University, No 800, Dongchuan Road, Shanghai 200240, People’s Republic of China, Email yuanweien@ 123456126.com
                [*]

                These authors contributed equally to this work

                Article
                dddt-11-1401
                10.2147/DDDT.S134808
                5428756
                28507428
                f170fcbb-5a07-489a-8a66-6aadfd3bb3c7
                © 2017 Zhang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                propranolol,infantile hemangioma,β-blockers,oral propranolol,intervention studies

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