Original Article
The role of propranolol in the treatment of infantile hemangioma
O papel do propranolol no tratamento dos hemangiomas em idade pediátrica
Sérgio Laranjo
, Glória Costa, Filipa Paramés, Isabel Freitas, José Diogo Martins, Conceição Trigo, Fátima F. Pinto
Autor para correspondência
Serviço de Cardiologia Pediátrica, Hospital de Santa Marta, Centro Hospitalar Lisboa Central, EPE, Lisboa, Portugal
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10257
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"apellidos" => "Pinto" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Serviço de Cardiologia Pediátrica, Hospital de Santa Marta, Centro Hospitalar Lisboa Central, EPE, Lisboa, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "O papel do propranolol no tratamento dos hemangiomas em idade pediátrica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 540 "Ancho" => 1500 "Tamanyo" => 85412 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A four-month-old girl who presented with a large hemangioma on the left upper eyelid, showing complete involution of the lesions after five months of oral propranolol. M: months.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Infantile hemangiomas are the most common benign vascular tumors in infancy, affecting 5–10% of the population. Females are affected more often than males, with a ratio of 3:1.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Typically they present shortly after birth, undergo a period of rapid proliferation, and then slowly involute over many years.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Although most are small cutaneous vascular malformations of the face,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> they can also be large, disfiguring lesions with serious complications. Infants with large hemangiomas, especially those with a segmental distribution or hemangiomatosis, are at particular risk for extracutaneous complications. They may also be associated with other congenital malformations, such as PHACE,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> PELVIS<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> or SACRAL syndrome.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In most cases only parental education and reassurance are required. Although 85–90% of all infantile hemangiomas eventually undergo spontaneous involution, a minority can still cause disfigurement and serious complications, depending on their location (obstruction of airways and vision), size, and speed of regression, which can be associated with painful ulcerations and hemorrhage or even high-output heart failure.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,8,9</span></a> Hemangiomas with the potential to threaten a child's life or vital functions and those that ulcerate or cause substantial disfigurement warrant treatment,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> which may be medical or surgical, or a combination of both.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">At present there is no gold standard medical treatment. Unfortunately, current therapeutic approaches have limited success and significant adverse effects that limit their use.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–16</span></a> Since Léauté-Labrèze's accidental observation<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> of the anti-proliferative effect of propranolol on infantile hemangiomas, propranolol has become increasingly popular<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> as a successful therapeutic option, with fewer side effects than other treatments.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We present a single-center study describing the efficacy and safety of propranolol in children with infantile hemangiomas.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Inclusion and exclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">All patients were referred by their pediatric dermatologist or pediatric surgeon to a pediatric cardiology department for baseline cardiovascular assessment prior to propranolol therapy, and cardiovascular assessment during therapy.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with infantile hemangiomas were considered for propranolol treatment if they met the following criteria: eyelid involvement with risk of ocular occlusion or compression; airway obstruction; or large hemangioma with significant disfigurement or ulceration. Patients previously treated with other therapeutic modalities were also considered candidates for inclusion if the previous treatment had failed. Exclusion criteria included cardiac anomalies, central nervous system vascular anomalies as in PHACE syndrome, hypoglycemia, asthma or bronchospasm. While the study focused on infants, patients over one year of age were enrolled if their hemangiomas showed signs of continued proliferation or had shown no signs of resolution since infancy.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Treatment protocol</span><p id="par0035" class="elsevierStylePara elsevierViewall">All patients underwent full cardiac examination before treatment, which included clinical examination, heart rate and blood pressure measurements, electrocardiogram, and echocardiogram. A baseline fingerstick blood glucose level was obtained. Further monitoring during the study included a weekly re-evaluation while the dose was being titrated to its maximum target dose, at weeks 1–4. Parents were instructed to look for signs of lethargy, poor feeding or wheezing. After the first month, monthly follow-up visits were scheduled until the end of the treatment for severity scoring of the hemangiomas, physical assessment and monitoring for adverse effects.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Dosage and duration</span><p id="par0040" class="elsevierStylePara elsevierViewall">Propranolol was given at a starting dose of 1 mg/kg/day, in two or three divided doses, and titrated to a target dose of 2–3 mg/kg per day according to clinical response.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Severity scoring system</span><p id="par0045" class="elsevierStylePara elsevierViewall">A photograph-based severity scoring scale was used. Frontal and lateral pictures of every patient were taken before treatment and at every follow-up visit.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">Starting in 2010 thirty patients were included in this study, of whom 15 (50%) were female; none were born prematurely. Superficial hemangioma was the predominant type, observed in 25 (83%) patients, whereas in three (10%) the hemangiomas had a segmental distribution (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The most frequent location was facial-cervical (70%). Propranolol was started at a median age of six months (1–63 months); the oldest patient was five years old. The mean target propranolol dose was 2.8 mg/kg/day (range 2.5–3.2 mg/kg/day). The mean duration of therapy was 12 months. All patients experienced immediate color changes and effects on the rate of hemangioma growth; in all patients a reduction of its size and volume was seen (<a class="elsevierStyleCrossRefs" href="#fig0005">Figures 1–3</a>). No adverse effects were identified or reported by the patients or their parents. Propranolol was discontinued in five patients when the residual lesions ceased to respond to therapy; one had a slight relapse but it was not necessary to re-start propranolol.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In this group of patients propranolol therapy had similar effectiveness regardless of age at initiation of treatment (before or after six months of age). It was equally effective in hemangiomas considered to be beyond the proliferative phase. Also, segmental and nonsegmental, superficial, mixed, and deep infantile hemangiomas showed a similar response to propranolol (<a class="elsevierStyleCrossRefs" href="#fig0005">Figures 1–3</a>).</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">In our experience propranolol appears to be a useful treatment for severe or complicated infantile hemangiomas, achieving a rapid and significant reduction in size. This reduction was mainly achieved during the first 20 weeks of treatment, and further treatment induced a less dramatic therapeutic effect. In this series of patients propranolol was equally effective in both segmental and nonsegmental infantile hemangiomas and in those beyond the proliferative phase.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Infantile hemangiomas have a predictable natural history.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,20</span></a> The majority are not present at birth. A hallmark of infantile hemangioma is its dramatic growth after birth, by diffuse proliferation of immature endothelial cells, followed by spontaneous regression. The majority of children with infantile hemangiomas require no treatment as the lesions regress over time and produce no long-term scarring; regression is complete in 50% of five-year-old patients and 90% of nine-year-olds.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In approximately 10% of cases there can be serious or life-threatening hemangiomas, requiring treatment.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Current treatment options for complicated hemangiomas include various medical or surgical modalities. Until recently, the mainstay of treatment for infantile hemangiomas was corticosteroids in various forms, including topical, intralesional, and oral formulations, the most common being oral prednisolone.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Only in complicated or refractory hemangioma cases have other treatment modalities been considered, such as chemotherapeutic agents (vincristine, interferon-alpha), laser therapy, surgery or a combination of these, and, most recently, propranolol. Each treatment option has limited therapeutic benefit, with its own side effects and risks. However, in the past three years there have been more than 120 reports of the efficacy of oral beta-blockers, usually propranolol, as a highly effective therapeutic option for infantile hemangioma and its complications.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,21–23</span></a> Furthermore, it has been demonstrated that propranolol therapy is superior to oral corticosteroid treatment, the former standard therapy for infantile hemangioma, and should be considered the first-line agent given its safety and efficacy.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Possible explanations for the therapeutic effect of propranolol on hemangiomas include vasoconstriction by decreasing the release of nitric oxide, which is immediately visible as a change in color, associated with palpable tissue softening. Other suggestions are down-regulation of proangiogenic signals such as VEGF, bFGF, MMP-9 and HBMEC, and induction of apoptosis in proliferating capillary endothelial cells.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25,26</span></a> A large international randomized clinical trial is underway, but many are already advocating its use as a first-line treatment for infantile hemangiomas, in terms of both safety and efficacy.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21,27</span></a> Its effects were first discovered by chance by Léauté-Labrèze et al. in 2008.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Subsequent reports have emphasized propranolol's role not only in halting hemangioma growth but also in diminishing their size.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Most groups have used a maximum target dose of 1–3 mg/kg/day.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11,17,18,21,22,28–37</span></a> However, there are no established consistent protocols, particularly regarding the timing of treatment tapering and discontinuation.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11,17–19,21,22,28–37</span></a> There is also no consensus regarding the relapse rate after discontinuation, with some studies showing no relapses,<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30–32</span></a> while others report minor recurrences.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,18,36</span></a> In our short series only one of the patients in whom propranolol was tapered showed a slight, non-significant, relapse, with no need to re-start treatment.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Until recently, the most common approach for patients with infantile hemangiomas in the post-proliferative phase was “active non-intervention”.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> In our series, propranolol improved esthetics in all patients, giving scope for more conservative surgical intervention in the future if necessary. These findings are consistent with those reported by Zvulunov et al.,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Schupp et al.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> and Celik et al.,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> who reported the results of propranolol therapy for hemangiomas beyond the proliferative phase, and imply that oral propranolol therapy may be warranted in children with late residual infantile hemangiomas, prior to any surgical intervention.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Still, the most impressive responses occurred in the youngest patients, a finding that is consistent with the natural history of hemangioma, in which 80% of its size is reached by six months of age, and justifies referring such cases earlier for optimal therapeutic response.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The appropriate monitoring protocol for assessment of adverse effects in infants with infantile hemangiomas, before and during propranolol treatment, has not been established.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> The potential side effects of beta-blockers, which are well known and include bradycardia, hypotension, and hypoglycemia,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,18,33,40–44</span></a> must be borne in mind. Propranolol is also contraindicated in patients with asthma, and it is not recommended during episodes of bronchiolitis.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,45</span></a> Notwithstanding, propranolol appears to be a safe drug when correctly administered. No adverse effects were observed in our series; none of our patients had symptoms of hypoglycemia or hypotension. However, until larger clinical trials are completed, potential adverse events should be borne in mind and consultation with local specialists such as pediatric cardiologists is recommended prior to initiating treatment. Patients with PHACE syndrome and severe cerebrovascular disease are, at least in theory, at risk for brain ischemia even with the relatively mild hypotension induced by beta-blockers.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The risks and benefits in this subset of patients must be weighed carefully. <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a> summarizes our treatment algorithm based on our experience.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion, a better understanding of the mechanisms of propranolol-induced regression of infantile hemangiomas will provide opportunities to design even more successful therapies. Meanwhile, propranolol appears to be a uniquely effective and safe therapy for infantile hemangiomas, including in the post-proliferative phase, and should be considered the first-line therapy in this setting.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Ethical disclosures</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Protection of human and animal subjects</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Confidentiality of data</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Right to privacy and informed consent</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres347619" "titulo" => array:6 [ 0 => "Abstract" 1 => "Introduction" 2 => "Objective" 3 => "Methods" 4 => "Results" 5 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec329287" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres347618" "titulo" => array:6 [ 0 => "Resumo" 1 => "Introdução" 2 => "Objetivo" 3 => "Métodos" 4 => "Resultados" 5 => "Conclusões" ] ] 3 => array:2 [ "identificador" => "xpalclavsec329286" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Inclusion and exclusion criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Treatment protocol" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Dosage and duration" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Severity scoring system" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0045" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-04-15" "fechaAceptado" => "2013-10-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec329287" "palabras" => array:2 [ 0 => "Infantile hemangioma" 1 => "Propranolol" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec329286" "palabras" => array:2 [ 0 => "Hemangioma infantil" 1 => "Propranolol" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Infantile hemangioma (IH) is one of the most common childhood tumors. There are various medical or surgical therapeutic options, all with suboptimal results. Recently, the successful use of propranolol for involution of IH was described. We report the results of a single-center experience with this therapeutic option.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To prospectively assess the efficacy and safety of propranolol in children with infantile hemangioma.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We performed a prospective analysis of clinical data of all patients with IH referred to a pediatric cardiology center for baseline cardiovascular assessment prior to propranolol therapy. Propranolol was given at a starting dose of 1 mg/kg/day and titrated to a target dose of 2–3 mg/kg/day according to clinical response. Efficacy was assessed through a photograph-based severity scoring scale. Safety was assessed by collecting data regarding significant side effects.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Starting in 2010, 30 patients (15 female) were referred for propranolol treatment of IH, at a median age of six months (1–63 months). The mean target propranolol dose was 2.8 mg/kg/day, with a mean duration of therapy of 12 months. All patients experienced significant reduction of IH size and volume. There were no side effects.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In our experience propranolol appears to be a useful and safe treatment option for severe or complicated IH, achieving a rapid and significant reduction in their size. No adverse effects were observed, although until larger clinical trials are completed, potential adverse events should be borne in mind and consultation with local specialists is recommended prior to initiating treatment.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introdução</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Os hemangiomas são a lesão tumoral cutânea mais frequente em idade pediátrica. Até ao momento todas as opções terapêuticas (tanto médicas como cirúrgicas) têm resultados sub-ótimos. Recentemente, foi descrita a utilização de propranolol para tratamento dos hemangiomas. Relatamos os resultados da nossa experiência com esta opção terapêutica.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Avaliação prospetiva da eficácia e segurança de propranolol em crianças com hemangioma infantil.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Avaliação prospetiva de todos os doentes com hemangioma referenciados para avaliação cardiovascular prévia ao início de terapêutica com propranolol. O propranolol foi administrado numa dose inicial de 1 mg/kg/dia e titulada para uma dose alvo de 2–3 mg/kg/dia, de acordo com a resposta clínica. A eficácia foi avaliada através de uma escala fotográfica. A segurança foi avaliada através da recolha de dados sobre os efeitos secundários significativos.</p> <span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Desde 2010, 30 crianças (15 do sexo feminino) com hemangiomas foram referenciados para avaliação cardiovascular prévia ao início de terapêutica beta-bloqueante, com uma idade média de 6 meses (1-63 meses). A dose alvo média atingida foi de 2,8 mg / kg / dia, com uma duração média de tratamento de 12 meses. Em todos os doentes se verificou uma redução significativa das dimensões e volume dos hemangiomas. Não foram observados efeitos colaterais.</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclusões</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Na nossa experiência, o propranolol é uma opção eficaz e segura para o tratamento de hemangiomas extensos ou complicados, obtendo-se uma redução rápida e significativa das suas dimensões. Não foram observados efeitos adversos contudo, recomenda-se a avaliação cardiovascular sistemática, prévia ao início de terapêutica com propranolol.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 540 "Ancho" => 1500 "Tamanyo" => 85412 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">A four-month-old girl who presented with a large hemangioma on the left upper eyelid, showing complete involution of the lesions after five months of oral propranolol. M: months.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 630 "Ancho" => 1399 "Tamanyo" => 102441 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A two-month-old boy who presented with hemangioma on the left thigh, showing complete involution of the lesion on thigh and scrotum after eight months of therapy. M: months.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 595 "Ancho" => 1800 "Tamanyo" => 146197 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">A ten-month-old boy with hemangioma on the right patella and upper right leg, showing a fair response after 18 months of therapy. M: months.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 3137 "Ancho" => 2088 "Tamanyo" => 373933 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Flowchart showing proposed work-up and treatment protocol.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n=30 \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Female:male ratio</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1:1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Type of hemangioma</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Superficial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Deep \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Distribution of hemangioma</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Head \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Periocular/eyelid involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Peribuccual involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thoracic involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Limb involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Baseline assessment (blood pressure, fasting blood glucose, heart rate)</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Electrocardiogram pre-treatment</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Echocardiogram pre-treatment</span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Normal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Abnormal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab518333.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" 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| 2024 Junho | 44 | 23 | 67 |
| 2024 Maio | 50 | 26 | 76 |
| 2024 Abril | 51 | 33 | 84 |
| 2024 Maro | 60 | 12 | 72 |
| 2024 Fevereiro | 74 | 27 | 101 |
| 2024 Janeiro | 51 | 30 | 81 |
| 2023 Dezembro | 52 | 28 | 80 |
| 2023 Novembro | 56 | 27 | 83 |
| 2023 Outubro | 35 | 26 | 61 |
| 2023 Setembro | 41 | 18 | 59 |
| 2023 Agosto | 47 | 17 | 64 |
| 2023 Julho | 37 | 19 | 56 |
| 2023 Junho | 60 | 9 | 69 |
| 2023 Maio | 82 | 26 | 108 |
| 2023 Abril | 32 | 8 | 40 |
| 2023 Maro | 68 | 18 | 86 |
| 2023 Fevereiro | 50 | 16 | 66 |
| 2023 Janeiro | 47 | 12 | 59 |
| 2022 Dezembro | 47 | 16 | 63 |
| 2022 Novembro | 64 | 20 | 84 |
| 2022 Outubro | 48 | 21 | 69 |
| 2022 Setembro | 25 | 18 | 43 |
| 2022 Agosto | 25 | 29 | 54 |
| 2022 Julho | 43 | 28 | 71 |
| 2022 Junho | 31 | 20 | 51 |
| 2022 Maio | 30 | 25 | 55 |
| 2022 Abril | 53 | 27 | 80 |
| 2022 Maro | 29 | 29 | 58 |
| 2022 Fevereiro | 33 | 21 | 54 |
| 2022 Janeiro | 47 | 20 | 67 |
| 2021 Dezembro | 33 | 33 | 66 |
| 2021 Novembro | 44 | 37 | 81 |
| 2021 Outubro | 74 | 39 | 113 |
| 2021 Setembro | 63 | 35 | 98 |
| 2021 Agosto | 61 | 31 | 92 |
| 2021 Julho | 38 | 22 | 60 |
| 2021 Junho | 40 | 21 | 61 |
| 2021 Maio | 35 | 23 | 58 |
| 2021 Abril | 68 | 37 | 105 |
| 2021 Maro | 83 | 19 | 102 |
| 2021 Fevereiro | 84 | 19 | 103 |
| 2021 Janeiro | 49 | 12 | 61 |
| 2020 Dezembro | 41 | 9 | 50 |
| 2020 Novembro | 52 | 20 | 72 |
| 2020 Outubro | 41 | 12 | 53 |
| 2020 Setembro | 67 | 12 | 79 |
| 2020 Agosto | 40 | 8 | 48 |
| 2020 Julho | 53 | 7 | 60 |
| 2020 Junho | 39 | 4 | 43 |
| 2020 Maio | 61 | 7 | 68 |
| 2020 Abril | 48 | 12 | 60 |
| 2020 Maro | 44 | 8 | 52 |
| 2020 Fevereiro | 129 | 34 | 163 |
| 2020 Janeiro | 46 | 10 | 56 |
| 2019 Dezembro | 58 | 8 | 66 |
| 2019 Novembro | 54 | 7 | 61 |
| 2019 Outubro | 38 | 2 | 40 |
| 2019 Setembro | 112 | 11 | 123 |
| 2019 Agosto | 35 | 7 | 42 |
| 2019 Julho | 58 | 11 | 69 |
| 2019 Junho | 57 | 9 | 66 |
| 2019 Maio | 40 | 11 | 51 |
| 2019 Abril | 44 | 22 | 66 |
| 2019 Maro | 152 | 15 | 167 |
| 2019 Fevereiro | 87 | 19 | 106 |
| 2019 Janeiro | 71 | 13 | 84 |
| 2018 Dezembro | 108 | 14 | 122 |
| 2018 Novembro | 196 | 14 | 210 |
| 2018 Outubro | 282 | 11 | 293 |
| 2018 Setembro | 72 | 9 | 81 |
| 2018 Agosto | 63 | 19 | 82 |
| 2018 Julho | 43 | 15 | 58 |
| 2018 Junho | 59 | 4 | 63 |
| 2018 Maio | 84 | 9 | 93 |
| 2018 Abril | 54 | 9 | 63 |
| 2018 Maro | 69 | 11 | 80 |
| 2018 Fevereiro | 49 | 3 | 52 |
| 2018 Janeiro | 38 | 9 | 47 |
| 2017 Dezembro | 78 | 11 | 89 |
| 2017 Novembro | 47 | 6 | 53 |
| 2017 Outubro | 57 | 11 | 68 |
| 2017 Setembro | 49 | 7 | 56 |
| 2017 Agosto | 51 | 13 | 64 |
| 2017 Julho | 44 | 11 | 55 |
| 2017 Junho | 54 | 12 | 66 |
| 2017 Maio | 43 | 9 | 52 |
| 2017 Abril | 31 | 2 | 33 |
| 2017 Maro | 35 | 18 | 53 |
| 2017 Fevereiro | 152 | 8 | 160 |
| 2017 Janeiro | 41 | 4 | 45 |
| 2016 Dezembro | 37 | 12 | 49 |
| 2016 Novembro | 75 | 10 | 85 |
| 2016 Outubro | 80 | 6 | 86 |
| 2016 Setembro | 43 | 12 | 55 |
| 2016 Agosto | 28 | 5 | 33 |
| 2016 Julho | 10 | 9 | 19 |
| 2016 Junho | 24 | 9 | 33 |
| 2016 Maio | 3 | 4 | 7 |
| 2016 Abril | 72 | 2 | 74 |
| 2016 Maro | 124 | 11 | 135 |
| 2016 Fevereiro | 126 | 30 | 156 |
| 2016 Janeiro | 121 | 16 | 137 |
| 2015 Dezembro | 108 | 9 | 117 |
| 2015 Novembro | 109 | 13 | 122 |
| 2015 Outubro | 110 | 9 | 119 |
| 2015 Setembro | 91 | 11 | 102 |
| 2015 Agosto | 114 | 14 | 128 |
| 2015 Julho | 139 | 9 | 148 |
| 2015 Junho | 87 | 7 | 94 |
| 2015 Maio | 96 | 29 | 125 |
| 2015 Abril | 85 | 16 | 101 |
| 2015 Maro | 100 | 4 | 104 |
| 2015 Fevereiro | 134 | 6 | 140 |
| 2015 Janeiro | 85 | 19 | 104 |
| 2014 Dezembro | 101 | 9 | 110 |
| 2014 Novembro | 80 | 16 | 96 |
| 2014 Outubro | 109 | 18 | 127 |
| 2014 Setembro | 85 | 13 | 98 |
| 2014 Agosto | 96 | 29 | 125 |
| 2014 Julho | 105 | 65 | 170 |
| 2014 Junho | 17 | 16 | 33 |
Mostrar tudo
