RESUMEN
OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.
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Coartación Aórtica , Anomalías del Ojo , Síndromes Neurocutáneos , Humanos , Lactante , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Síndromes Neurocutáneos/complicaciones , Anomalías del Ojo/complicaciones , Coartación Aórtica/complicaciones , Calidad de Vida , Estudios Transversales , CefaleaRESUMEN
BACKGROUND: PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated with 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. OBJECTIVES: To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. METHODS: Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. RESULTS: MiTES presents in the first year of life; in all cases the condition regresses over the first decade, leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12 CIP are rarely found. The genotype-phenotype study of the PRDM12 polyalanine tract shows that having 7-15 alanines is normal; 16-18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. CONCLUSIONS: We provide diagnostic criteria for MiTES and improved longitudinal data. MiTES and CIP are distinct phenotypes, despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells. We hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12.
Midfacial toddler excoriation syndrome (MiTES) causes facial itching and scratching in babies during their first year of life. MiTES tends to improve over the time period of approximately 10â years, but it can leave scars. Congenital insensitivity to pain (CIP) is a condition where a person cannot feel pain and is present from birth. This study looked at two conditions: MiTES and CIP. We specifically investigated changes in a gene called PRDM12, focusing on a part of the gene called the polyalanine tract a sequence of many alanines (alanine is a type of amino acid). We discovered that the normal range for this sequence is between 7 and 15 alanines. If there are 16 to 18 alanines, it is associated with MiTES and causes the PRDM12 protein to clump together inside the cell. However, if there are 19 alanines, it leads to CIP, and the PRDM12 protein clumps together and moves to the cytoplasm, where it should not be. We found new evidence to suggest that MiTES is a disease where proteins clump together. Overall, our study findings show that despite there only being a small change in the same gene, MiTES and CIP are very different conditions.
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Fenotipo , Humanos , Masculino , Femenino , Preescolar , Lactante , Genotipo , Niño , Síndrome , Proteínas del Tejido Nervioso/genética , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Neuropatías Hereditarias Sensoriales y Autónomas/diagnóstico , Proteínas PortadorasRESUMEN
OBJECTIVE: To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm. METHODS: This single-center, retrospective study of infants diagnosed with SCFN at Ann & Robert H. Lurie Children's Hospital of Chicago from 2009 to 2019. RESULTS: Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age. CONCLUSION: Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (>1.6 mmol/L), or persistently elevated levels (>6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.
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Necrosis Grasa , Hipercalcemia , Embarazo , Recién Nacido , Niño , Humanos , Femenino , Hipercalcemia/complicaciones , Calcio , Estudios Retrospectivos , Cesárea , Grasa Subcutánea , Necrosis Grasa/complicacionesRESUMEN
BACKGROUND/OBJECTIVES: We sought to describe the experience among members of the Hemangioma Investigator Group with pulsed dye laser (PDL) in the treatment of nonulcerated infantile hemangioma (IH) in pediatric patients in the pre- and post-beta-blocker era. METHODS: A multicenter retrospective cohort study was conducted in patients with nonulcerated IH treated with laser therapy. Patient demographics, IH characteristics, indications for/timing of laser therapy, as well as laser parameters were collected. Responses to laser therapy were evaluated using a visual analog scale (VAS). RESULTS: One hundred and seventeen patients with IH were treated with PDL. 18/117 (15.4%) had early intervention (defined as <12 months of life), and 99/117 (84.6%) had late intervention (≥12 months of life). In the late intervention group, 73.7% (73/99) had additional medical management of their IH. The mean age at PDL initiation for the late intervention group was 46.7 ± 35.3 months of life (range 12-172 months) with total number of treatments to maximal clearing of 4.2 ± 2.8 (range 1-17). Those who received propranolol prior to PDL received fewer sessions (1.1 fewer sessions, approaching significance [p = .056]). On the VAS, there was a mean 85% overall improvement compared to baseline (range 18%-100%), with most improvement noted in erythema and/or telangiectasias. The incidence of adverse effects was 6/99 (6.1%). CONCLUSIONS: PDL is a useful tool in the treatment of IH, with notable improvement of telangiectasia and erythema and low risk of complications. PDL is often introduced after the maximal proliferative phase.
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Hemangioma Capilar , Hemangioma , Láseres de Colorantes , Humanos , Niño , Estudios Retrospectivos , Láseres de Colorantes/uso terapéutico , Hemangioma Capilar/radioterapia , Hemangioma Capilar/cirugía , Hemangioma/radioterapia , Hemangioma/cirugía , Hemangioma/etiología , Antagonistas Adrenérgicos beta , Resultado del TratamientoRESUMEN
Reactive, nonsexually related acute genital ulceration, also known as Lipschütz ulcer, is a nonsexually related ulceration involving the vulva, most commonly affecting girls and adolescent women in response to infection. Herein, we describe 3 female patients with acute genital ulceration occurring after severe acute respiratory syndrome coronavirus 2 vaccination or natural infection.
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COVID-19 , Úlcera , Adolescente , COVID-19/prevención & control , Femenino , Humanos , SARS-CoV-2 , Úlcera/etiología , Vacunación , VulvaRESUMEN
Prompt and accurate diagnosis of infantile hemangiomas is essential to prevent potential complications. This can be difficult due to high rates of misdiagnosis and poor access to pediatric dermatologists. In this study, we trained an artificial intelligence algorithm to diagnose infantile hemangiomas based on clinical images. Our algorithm achieved a 91.7% overall accuracy in the diagnosis of facial infantile hemangiomas.
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Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Niño , Humanos , Inteligencia Artificial , Neoplasias Cutáneas/diagnóstico , Hemangioma Capilar/diagnóstico , Hemangioma/diagnóstico , AlgoritmosRESUMEN
BACKGROUND/OBJECTIVES: The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS: Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS: The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS: Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.
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COVID-19 , Hemangioma Capilar , Hemangioma , Telemedicina , COVID-19/epidemiología , Estudios Transversales , Hemangioma/diagnóstico , Hemangioma/terapia , Humanos , PandemiasRESUMEN
Lichen nitidus is a benign skin condition of unknown etiology that is classically described on the trunk, extremities, and genitalia as pinpoint flat-topped papules. In dark-skinned persons, the lesions may appear shiny or even hypopigmented. Lichen nitidus is less often described on the face. We describe a series of pediatric patients with skin of color who presented with the chief complaint of facial skin lightening and had associated clinical findings consistent with lichen nitidus.
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Hipopigmentación , Liquen Nítido , Niño , Cara , Humanos , Hipopigmentación/diagnóstico , Liquen Nítido/diagnóstico , Piel , Pigmentación de la PielRESUMEN
BACKGROUND/OBJECTIVES: Infantile hemangiomas (IHs) are common benign vascular tumors of infancy. IHs tend to grow in the first few months of life and then gradually involute over years, often leaving fibrofatty residua or textural changes in their place. Classically, these lesions are painless throughout their entire natural history; however, we now report on seven patients with involuted IH with intermittent but persistent sensory symptoms. METHODS: This is a multicenter case series in which members of the Birthmarks Focused Study Group of the Pediatric Dermatology Research Alliance (PeDRA) and the Hemangioma Investigator Group contributed patients with IH and dysesthesias from their clinical practices. Charts were then reviewed to document clinical details. RESULTS: Seven patients were included, presenting at an average age of 14.6 years (range 3-48 years) for complaints related to discomfort in the region of involuted IH. The majority (6/7) reported pain or tenderness to the area. One patient reported pruritus. All patients reported intermittent symptoms. The length of symptoms ranged between 4 months and 5 years. Treatment was attempted in 5/7 patients. Ice, oral propranolol, topical capsaicin, and intralesional triamcinolone partially improved symptoms. CONCLUSIONS: Persistent cutaneous dysesthesias were present in seven patients, in most cases many years after completion of involution. Further research is needed to fully elucidate the pathophysiology and optimal treatments for this IH complication.
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Hemangioma Capilar , Hemangioma , Neoplasias Cutáneas , Administración Cutánea , Adolescente , Adulto , Niño , Preescolar , Hemangioma/complicaciones , Hemangioma/diagnóstico , Hemangioma/tratamiento farmacológico , Hemangioma Capilar/tratamiento farmacológico , Humanos , Lactante , Persona de Mediana Edad , Parestesia , Propranolol/uso terapéutico , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del Tratamiento , Adulto JovenRESUMEN
Restrictive dermopathy (RD) is a rare and lethal laminopathy caused by mutations in LMNA or ZMPSTE24. This series reports 3 patients with RD and reviews the literature of the 113 previously reported cases, including highlights of the unique constellation of clinical findings in RD, as well as histologic, radiographic, and genetic features. Early recognition of these characteristic features is vital to establish a prompt diagnosis and provide adequate family counseling for this terminal condition.
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Laminopatías , Proteínas de la Membrana , Metaloendopeptidasas , Humanos , Laminopatías/diagnóstico , Laminopatías/genética , Proteínas de la Membrana/genética , Metaloendopeptidasas/genética , MutaciónRESUMEN
BACKGROUND: Data regarding the treatment of periorificial dermatitis with topical calcineurin inhibitors (TCI) in the pediatric population are limited. OBJECTIVE: To assess the clinical utility of TCI in pediatric patients with periorificial dermatitis. METHODS: A retrospective medical record review of all pediatric patients with periorificial dermatitis treated with TCIs was performed. Follow-up via telephone was performed to capture missing data. RESULTS: A total of 132 patients met the inclusion criteria. The median age at diagnosis was 4.2 years (interquartile range, 2.3-8.2). The median follow-up was 5.2 months (interquartile range, 2.1-11.7). Seventy-two patients had evaluable follow-up data. Of these, 48 (67%) patients were treated with TCI alone, 12 (16.7%) were treated with a combination of TCI and topical metronidazole, and 9 (12.5%) were treated with a combination of TCI and a systemic antibiotic. Complete response was noted in 68.8% of patients treated with TCI alone, in 75% of patients treated with TCI and metronidazole, and in 77.8% of patients treated with TCI and a systemic antibiotic. Adverse events were rare and mild in severity. CONCLUSION: Topical calcineurin inhibitors are an effective therapeutic option for pediatric patients with periorificial dermatitis and were well tolerated in this cohort.
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Inhibidores de la Calcineurina/administración & dosificación , Dermatitis/tratamiento farmacológico , Tacrolimus/análogos & derivados , Tacrolimus/administración & dosificación , Administración Tópica , Niño , Preescolar , Ojo , Femenino , Humanos , Masculino , Boca , Nariz , Estudios RetrospectivosRESUMEN
Deep forehead lipomas are rare in children and may be confused with other more concerning soft tissue masses. We describe four children with deep forehead lipomas, diagnosed between 2 months and 1 year of age, three of them congenital. Notable findings included association with intracranial lipoma and seizures in one patient and the development of marked alopecia overlying the lipoma in another. While deep forehead lipomas may become less visible over time, alopecia and non-syndromic extracutaneous involvement may be important associations.
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Frente , Lipoma , Niño , Humanos , Lipoma/diagnósticoRESUMEN
The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Hemangioma/terapia , Neumonía Viral/epidemiología , Neoplasias Cutáneas/terapia , Telemedicina , Antagonistas Adrenérgicos beta/uso terapéutico , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Hemangioma/patología , Humanos , Lactante , Recién Nacido , Pandemias/prevención & control , Selección de Paciente , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2 , Neoplasias Cutáneas/patologíaRESUMEN
OBJECTIVE: To characterize the risk for ocular complications in patients with PHACE syndrome. STUDY DESIGN: This study included consecutive patients with PHACE syndrome who were seen at Lurie Children's Hospital of Chicago from January 2000 through May 2017. A complete ophthalmic examination was performed in all patients, with extra attention for findings typically associated with PHACE syndrome. RESULTS: Thirty patients (67% female, median age of onset 0.08 months) were included: 38 (93%) demonstrated a segmental infantile hemangioma distribution. Twenty-one (70%) cases had a periocular involvement, and 47% had an infantile hemangioma with a deep component. Among 21 patients with periocular distribution, 9 had ocular complications secondary to the periocular location (mainly ptosis, nasolacrimal duct obstruction, and refractive errors), and one had an ocular complication specifically associated with PHACE syndrome (Horner syndrome). None of the patients without periocular distribution had an ocular complication. CONCLUSIONS: In patients with PHACE syndrome who have a periocular infantile hemangioma, a complete eye examination is recommended. Although specific ocular anomalies related to PHACE syndrome are rare, serious ocular complications secondary to the location of the hemangioma may be present. Eye examination in patients with PHACE syndrome without a periocular infantile hemangioma distribution is likely of low yield.
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Coartación Aórtica/complicaciones , Anomalías del Ojo/etiología , Síndromes Neurocutáneos/complicaciones , Chicago , Preescolar , Ojo/patología , Anomalías del Ojo/complicaciones , Anomalías del Ojo/epidemiología , Femenino , Hemangioma/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftment was documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57 months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlying mutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.
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Trasplante de Células Madre Hematopoyéticas , Quinasa I-kappa B/genética , Mutación/genética , Preescolar , Estudios de Cohortes , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Heterocigoto , Humanos , Lactante , Recién Nacido , Inflamación/patología , Enfermedades Inflamatorias del Intestino/etiología , FN-kappa B/metabolismo , Fenotipo , Transducción de Señal/genética , Análisis de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
BACKGROUND: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).
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Antagonistas Adrenérgicos beta/administración & dosificación , Hemangioma/tratamiento farmacológico , Propranolol/administración & dosificación , Administración Oral , Antagonistas Adrenérgicos beta/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hipotensión/inducido químicamente , Lactante , Masculino , Propranolol/efectos adversos , Resultado del TratamientoRESUMEN
Screening electrocardiography (ECG) before initiation of propranolol for treatment of infantile hemangiomas (IH) is controversial. A retrospective chart review was conducted to assess the utility of pretreatment ECG in infants with IH starting propranolol. Although nearly half of the ECGs were abnormal, no contraindications to treatment were identified from screening ECG, and no association was found between any of the reported side effects and abnormal ECG. These results support previously published data, and in a larger cohort, providing further confirmation that pretreatment ECG is not necessary in most infants with IH.