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      Intolerable side effects during propranolol therapy for infantile hemangioma: frequency, risk factors and management

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          Abstract

          Currently, propranolol is the most preferred systemic therapy for problematic infantile hemangiomas (IHs). However, the side effects such as bronchial hyperreactivity may be intolerable. The aim of this study was to evaluate the frequency, risk factors and management of intolerable side effects (ISEs) during propranolol therapy. In total, 1260 children were studied. The incidence of ISEs was 2.1% (26 patients). Severe sleep disturbance was the most common reason for propranolol cessation, accounting for 65.4% of cases. In total, 23 and 3 patients received atenolol and prednisolone as second-line therapy, respectively. Treatment response was observed in 92.3% (24/26) of cases (showing excellent or good response to therapy). No toxicity-related permanent treatment discontinuation occurred during atenolol or prednisolone therapy. In the univariate analysis, younger age, premature birth, and lower body weight were associated with ISEs ( P < 0.05). In the multivariate analysis, only age (95% confidence interval [CI]: 1.201–2.793, P = 0.009) and body weight (95% CI: 1.036–1.972, P = 0.014) were associated with ISEs. Our study suggests that ISEs are rare in patients with IHs who are treated with propranolol. Predictive factors for ISEs include younger age and lower body weight. Atenolol and prednisolone are effective and safe alternatives to propranolol in the treatment of refractory IHs.

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          Most cited references35

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          Growth characteristics of infantile hemangiomas: implications for management.

          Infantile hemangiomas often are inapparent at birth and have a period of rapid growth during early infancy followed by gradual involution. More precise information on growth could help predict short-term outcomes and make decisions about when referral or intervention, if needed, should be initiated. The objective of this study was to describe growth characteristics of infantile hemangioma and compare growth with infantile hemangioma referral patterns. A prospective cohort study involving 7 tertiary care pediatric dermatology practices was conducted. Growth data were available for a subset of 526 infantile hemangiomas in 433 patients from a cohort study of 1096 children. Inclusion criteria were age younger than 18 months at time of enrollment and presence of at least 1 infantile hemangioma. Growth stage and rate were compared with clinical characteristics and timing of referrals. Eighty percent of hemangioma size was reached during the early proliferative stage at a mean age of 3 months. Differences in growth between hemangioma subtypes included that deep hemangiomas tend to grow later and longer than superficial hemangiomas and that segmental hemangiomas tended to exhibit more continued growth after 3 months of age. The mean age of first visit was 5 months. Factors that predicted need for follow-up included ongoing proliferation, larger size, deep component, and segmental and indeterminate morphologic subtypes. Most infantile hemangioma growth occurs before 5 months, yet 5 months was also the mean age at first visit to a specialist. Recognition of growth characteristics and factors that predict the need for follow-up could help aid in clinical decision-making. The first few weeks to months of life are a critical time in hemangioma growth. Infants with hemangiomas need close observation during this period, and those who need specialty care should be referred and seen as early as possible within this critical growth period.
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            Initiation and use of propranolol for infantile hemangioma: report of a consensus conference.

            Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.
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              Diagnosis and Management of Infantile Hemangioma.

              Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its purpose is to update the pediatric community regarding recent discoveries in IH pathogenesis, treatment, and clinical associations and to provide a basis for clinical decision-making in the management of IH.
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                Author and article information

                Contributors
                jijiyuanyuan@163.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 March 2018
                9 March 2018
                2018
                : 8
                : 4264
                Affiliations
                [1 ]ISNI 0000 0004 1770 1022, GRID grid.412901.f, Division of Oncology, Department of Pediatric Surgery, , West China Hospital of Sichuan University, ; Chengdu, 610041 China
                [2 ]ISNI 0000 0004 1770 1022, GRID grid.412901.f, Pediatric Intensive Care Unit, Department of Critical Care Medicine, , West China Hospital of Sichuan University, ; Chengdu, 610041 China
                [3 ]ISNI 0000 0004 1757 9397, GRID grid.461863.e, Pediatric Intensive Care Unit, , West China Second University Hospital, Sichuan University, ; Chengdu, 610041 China
                [4 ]Department of Pediatric Surgery, Chengdu Shangjin Nanhu Hospital, Chengdu, 611730 China
                Article
                22787
                10.1038/s41598-018-22787-8
                5844887
                29523832
                4918c618-8826-4d8a-8c3a-5ae032739417
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 May 2017
                : 1 March 2018
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