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      Propranolol therapy of infantile hemangiomas: efficacy, adverse effects, and recurrence

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          Abstract

          Objective

          To evaluate the efficacy, adverse effects, and recurrence of oral propranolol for treatment of infantile hemangioma.

          Methods

          Participants were treated with oral propranolol three times daily, with inpatient monitoring of adverse effects. The starting dosage was 2 mg/kg per day, which had been for the remaining duration of treatment. Therapy duration was planned for 4–6 months; if there was significant relapse, the period of treatment was extended. A photograph based severity scoring assessment was performed by three observers to evaluate efficacy by visual analog scale (VAS).

          Results

          Sixty-one infants [median age 3.3 (1.2–8.1) months] were included in the study. The median follow-up-time was 15 (6–20) months and 53 patients completed treatment at a median age of 10.3 (8.4–18.1) months, after a duration of 8.5 (4.5–14) months. In all patients, there was significant fading of color [with a VAS of −9 (−6 to −9) after 6 months] and significant decrease in size of the infantile hemangiomas [with a VAS of −8 (−3 to −10) after 6 months]. We did not observe any life-threatening adverse effects. The therapy was interrupted due to temporary aggravation of pre-existing bronchial asthma in one child. Four cases presented partial recurrences.

          Conclusions

          Oral propranolol 2 mg/kg per day was a well-tolerated and effective treatment, mild adverse effects, and low recurrence for infantile hemangiomas. Propranolol should now be used as a first-line treatment in hemangiomas when intervention is required. Also, prospective studies should be needed in determining the most effective treatment dosage, optimum treatment duration, and exact mechanism of action of propranolol in future.

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          Most cited references25

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          Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action.

          Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85-90% regress spontaneously, some may become life- or function-threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, alpha-interferon or cyclophosphamide, all bearing the risk of serious side-effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long-term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1-3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long-term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.
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            Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia.

            Symptomatic neonatal hypoglycemia may be associated with later neurodevelopmental impairment. Brain injury patterns identified on early MRI scans and their relationships to the nature of the hypoglycemic insult and neurodevelopmental outcomes are poorly defined. We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months. White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects. Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.
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              Hemangiomas of infancy.

              Hemangiomas of infancy are unique, benign, pediatric tumors of endothelial cells characterized by an initial phase of rapid proliferation, followed by slow involution, often leading to complete regression. Although most of these tumors are small and innocuous, some may be may be life- or function-threatening, or have associated structural congenital anomalies. Uncertainties regarding their diagnosis or management often prompt referral to a dermatologist. The pathogenesis of hemangiomas of infancy is not well understood, but recent findings suggest a unique vascular phenotype with dysregulated vascular homeostasis. This article reviews new information regarding the pathogenesis of these tumors and highlights the more worrisome presentations, including syndromic hemangiomas, that are likely to be problematic. In addition, management strategies and treatment options are discussed. (J Am Acad Dermatol 2003;48:477-93.) At the completion of this learning activity, participants should be able to describe the clinical features of hemangiomas of infancy and potential complications as well as to understand the strengths and limitations of various treatment options.
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                Author and article information

                Contributors
                +13-80-2528653 , +15-91-3169386 , hnxiaoq@sina.com.cn
                +13-80-2528653 , +15-91-3169386 , gzzxwk@163.com
                Journal
                Pediatr Surg Int
                Pediatr. Surg. Int
                Pediatric Surgery International
                Springer-Verlag (Berlin/Heidelberg )
                0179-0358
                1437-9813
                22 March 2013
                22 March 2013
                June 2013
                : 29
                : 6
                : 575-581
                Affiliations
                Department of Plastic Surgery, General Hospital of Guangzhou Military Command (Liuhuaqiao Hospital), 111 Liu Hua Road, Yue Xiu District, 510010 Guangzhou, People’s Republic of China
                Article
                3283
                10.1007/s00383-013-3283-y
                3657346
                23519547
                7cb45716-1c8b-4549-8960-b748c38a577d
                © The Author(s) 2013

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 1 February 2013
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2013

                Pediatrics
                propranolol,infantile hemangiomas,efficacy,adverse effects,recurrence
                Pediatrics
                propranolol, infantile hemangiomas, efficacy, adverse effects, recurrence

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