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Background/objectives: Early referral and treatment of infantile hemangioma (IH) is a major challenge for treatment success. However, there is a lack of data supporting a specific threshold for initiating treatment with oral propranolol. The aim of this analysis was to find factors, such as age at treatment initiation, leading to a higher success rate with oral propranolol treatment., Methods: Based on data from the pivotal phase 2-3 clinical trial of oral propranolol in IH, we used Generalized Additive Model (GAM) charts with Generalized Linear Models (GLM), then a rule discovery algorithm, to identify sub-groups presenting a high probability of occurrence of the predefined outcome (i.e., success [complete or nearly complete resolution of the target hemangioma] at 6 months of treatment)., Results: Our analyses identified that patients who started oral propranolol 3 mg/kg/day before the age of 10 weeks had a success rate of 86%, higher than the 60% success rate for all patients that received the same regimen commencing after 10 weeks of age., Conclusions: Treatment initiation before 10 weeks of age was associated with a significantly higher rate of treatment success with oral propranolol 3 mg/kg/day. Infants with IH requiring treatment should be referred to an expert center and treated as soon as possible., (© 2022 Wiley Periodicals LLC.)

Infantile haemangiomas are very common benign tumours in the first months of life. They are mostly cutaneous; however, extracutaneous lesions are possible, and occur in very rare cases in the central nervous system. A European multicentre observational retrospective study was conducted in the last 5 years. Seven patients with intracranial or intraspinal infantile haemangiomas were selected and treated with oral propranolol. Propranolol was interrupted after complete or almost complete resolution of infantile haemangiomas. All patients tolerated the treatment well without side-effects. Central nervous system infantile haemangiomas are probably underestimated due to the frequent absence of symptoms and their spontaneous involution. However, they should be investigated in case of segmental cutaneous infantile haemangiomas, particularly on the head, neck, upper trunk, lumbar or sacral area in order to diagnosis intra-central nervous system involvement at an early stage.

Blue rubber bleb nevus syndrome (Bean syndrome) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations; gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with blue rubber bleb nevus syndrome. Somatic mutations were also identified in five of six individuals with sporadically occurring multifocal venous malformations. In contrast to common unifocal venous malformation, which is most often caused by the somatic L914F TIE2 mutation, multifocal forms are predominantly caused by double (cis) mutations, that is, two somatic mutations on the same allele of the gene. Mutations are identical in all lesions from a given individual. T1105N-T1106P is recurrent in blue rubber bleb nevus, whereas Y897C-R915C is recurrent in sporadically occurring multifocal venous malformation: both cause ligand-independent activation of TIE2, and increase survival, invasion, and colony formation when expressed in human umbilical vein endothelial cells., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to define the skin patterns at high risk for upper airway infantile haemangioma. A retrospective multicentre French observational study was conducted between January 2006 and January 2015 and all confirmed airway haemangioma were included. Thirty-eight patients with airway haemangioma from 9 centres were included. Thirty-one patients had a cutaneous or mucosal haemangioma: 21 with a location considered at high risk for airway haemangioma (large segmental mandibular haemangioma), 4 with a very mild facial involvement (lower lip or S1 (frontotemporal segment according to Haggstrom and Frieden)) and 6 with either lesions of the neck or body, or association of both. We report here the largest cohort of airway haemangioma. A third of patients do not completely fit with the definition of the high-risk area of airway haemangioma. Segmental lower lip and neck involvement also seem to be very suggestive areas. Clinicians must be able to recognize these areas.

Propranolol has been recently approved by health authorities to treat infantile haemangiomas (IH). Propranolol is indicated in infants less than 5months of age with an IH requiring systemic therapy: IH at life-threatening and/or functional risk, painful ulcerated IH and IH that may cause permanent disfigurement. Propranolol should be initiated by physicians who have expertise in the diagnosis, treatment and management of IH. In addition, the first intake and every escalation should be administrated in a controlled clinical setting where adequate facilities for handling of adverse reactions, including those requiring urgent measures, are available. Then a monthly monitoring with dose adjustment weight is mandatory by the family doctor. Parents should be informed of the risk of hypoglycaemia and bronchoconstriction, especially during respiratory infectious outbreaks. The recommended duration of treatment is 6months without tapering. Relapses are possible necessitating a second course of 3 to 6months of treatment., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Although propranolol has become the first-line therapy for infantile haemangiomas (IHs), no study has yet investigated factors associated with the risk of relapse in children with IH treated with propranolol after cessation of treatment., Objectives: To compare factors associated with the risk of relapse in children with IH treated with oral propranolol., Methods: We conducted a single-centre retrospective observational study. All files and photographs of patients with IH aged 5 months or less at the time of treatment initiation, and who were seen between 1 June 2008 and 31 December 2011 at the National Reference Center for rare skin diseases of Bordeaux, were retrospectively reviewed., Results: In total 158 children were included, of whom 118 had not relapsed and 40 had relapsed. Fifty-two patients were boys and 106 were girls (male : female ratio 1 : 2), and 19 had a segmental IH (12%). When conducting multivariate analysis, only IHs with a deep component and those with segmental distribution were independently associated with relapse., Conclusions: Our study shows that segmental IHs, as well as haemangiomas with a deeper component, are more at risk of relapse and should thus indicate closer follow-up after treatment interruption, and/or longer treatment., (© 2013 British Association of Dermatologists.)

Infantile hemangioma (IH) is not strictly speaking a tumor, but the result of anarchic postnatal vasculogenesis. Hypoxia seems to play an important role as a predisposing factor. IHs can present three clinical morphologies: superficial, deep, or mixed. Localized IHs are oval or round, circumscribed lesions, whereas segmental IHs extend across a large anatomic area with a geographic shape. Localized IHs are often benign, except when they are located near a noble structure such as the airways or the orbital area. Segmental IH may be associated with birth defects (PHACES syndrome and SACRAL syndrome). Clinical follow-up of infants with IH should be very careful in the first weeks of life since 80% of all IHs have reached their final size at 5 months of age. The main indications for treatment of IHs are: life-threatening conditions (heart failure, respiratory distress), functional risks (amblyopia, swallowing disorders, etc.), aesthetic risks (especially IH of the face localized on the nose, lips, etc.), and painful ulcerated IH. Beta-blockers, namely propranolol, have quickly become the first-line therapy of complicated IH. The treatment should be given as soon as possible to avoid sequelae., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Propranolol has become the treatment of choice of large and complicated infantile hemangiomas. There is a controversy concerning the safety of systemic propranolol. Here we show that topical use of the beta-blocker timolol can also inhibit the growth and promote regression of infantile hemangiomas. In this case series we treated 11 infantile hemangiomas in nine children including six preterm babies with the nonselective betablocker timolol. A timolol containing gel was manufactured from an ophthalmic formulation of timolol 0.5% eyedrops. This gel was applied using a standardized occlusive dressing (Finn-Chambers) containing approximately 0.25 mg of timolol. In all infants topical timolol was associated with growth arrest, a reduction in redness and thickness within the first 2 weeks. Seven hemangiomas showed almost complete resolution, and four became much paler and thinner. No data are available on the transdermal absorption of timolol. Even supposing complete absorption of timolol from the occlusive dressing, a maximum dose of 0.25 mg of timolol would result per day and hemangioma. Regression of infantile hemangiomas treated using 0.5% timolol gel in this case series occurred earlier than spontaneous regression which is generally not observed before the age of 9-12 months. The promising results need to be verified in prospective randomized trials on topical beta blocker administration for infantile hemangiomas which should address dose, duration, and mode of application., (© 2012 Wiley Periodicals, Inc.)

Background: Ulcerated infantile hemangiomas (IH) are a therapeutic challenge. Propranolol, a nonselective beta-blocker, was recently introduced as a novel treatment for IH., Objective: To evaluate our experience of propranolol in the management of ulcerated IH., Methods: A national, multicenter, retrospective, observational study was conducted. Data were collected from the medical charts of patients treated from 2008 to 2009 and supplemented by information obtained from parents during targeted telephone interviews., Results: Thirty-three infants with propranolol-treated ulcerated IH were included. The average time to complete ulceration healing was 4.3 weeks in 30 of 33 patients and was significantly faster for head-and-neck locations (P = .0354). The mean time to complete pain control was 14.5 days. Parents rated treatment as very effective for 27 of 31 patients and very well tolerated for 29 of 31 cases., Limitations: This was a retrospective uncontrolled study., Conclusion: Propranolol appears to be an effective and well-tolerated treatment for ulcerated IH., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

We report the rapid and dramatic efficacy of propranolol in 8 infants with infantile hepatic hemangiomas. The degree of response varied from a significant improvement to a complete resolution of hepatic lesions. Heart failure and hypothyroidism resolved, and hepatomegaly decreased. No side-effects of the drug were noted., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: Infantile hemangiomas (IHs) are the most-common soft-tissue tumors of infancy. We report the use of propranolol to control the growth phase of IHs., Methods: Propranolol was given to 32 children (21 girls; mean age at onset of treatment: 4.2 months) after clinical and ultrasound evaluations. After electrocardiographic and echocardiographic evaluations, propranolol was administered with a starting dose of 2 to 3 mg/kg per day, given in 2 or 3 divided doses. Blood pressure and heart rate were monitored during the first 6 hours of treatment. In the absence of side effects, treatment was continued at home and the child was reevaluated after 10 days of treatment and then every month. Ultrasound measurements were performed after 60 days of treatment., Results: Immediate effects on color and growth were noted in all cases and were especially dramatic in cases of dyspnea, hemodynamic compromise, or palpebral occlusion. In ulcerated IHs, complete healing occurred in <2 months. Objective clinical and ultrasound evidence of longer-term regression was seen in 2 months. Systemic corticosteroid treatment could be stopped within a few weeks. Treatment was administered for a mean total duration of 6.1 months. Relapses were mild and responded to retreatment. Side effects were limited and mild. One patient discontinued treatment because of wheezing., Conclusion: Propranolol administered orally at 2 to 3 mg/kg per day has a consistent, rapid, therapeutic effect, leading to considerable shortening of the natural course of IHs, with good clinical tolerance.

Infantile digital fibromatosis is a rare benign fibromatous tumor characterized by both its location on fingers and toes and its distinctive light microscopic appearance. However, treatment modalities are not yet standardized. Surgical excision had been preferred in the past but has the disadvantage of a high recurrence rate. More recently, isolated instances of spontaneous regression have been reported with a short follow-up. We report four children with infantile digital fibromatosis, who underwent spontaneous regression after clinical monitoring and long-term follow-up. We recommend regular follow-up in order to allow for intervention in case of functional impact on the affected extremities.

Unlabelled: Life-threatening complications of congenital haemangiomas are rare. A case of haemorrhage in a neonate is reported here. A neonate presented a congenital haemangioma of the limb complicated by a massive life-threatening haemorrhage. Colour ultrasonography showed a hypervascularized, highly haemodynamically active mass with a large, superficial drainage vein just under the ulceration. Surgical resection was performed with satisfactory postoperative outcome and no evidence of recurrence., Conclusion: Early surgical removal can be a good therapeutic option for complicated congenital haemangiomas.

Introduction: Alarming hemangiomas can be successfully treated with corticosteroids. The risk of hypertension is poorly documented in this setting. We conducted a prospective study in infants with hemangiomas treated with orally administered prednisone., Patients and Methods: Thirty-seven patients with rapidly growing complicated hemangiomas were enrolled between January 1998 and November 1999. Steroid dosages varied from 1 mg/kg/d to 5 mg/kg/d. Blood pressure measurements were performed first twice a month, then monthly at rest with a Critikon Dynamap device. Hypertension was defined as blood pressure superior to 110/60 mmHg, and borderline if superior to 110/60 mmHg on only one or two measurements., Results: Increased blood pressure was found in seven infants (19 p. 100). One infant had hypertension requiring specific treatment and blood pressure was borderline on six patients at one or two occasions. Cardiac ultrasound examination was performed in five patients revealing two cases of myocardic hypertrophy, which regressed after stopping steroids and without relationship to hypertension., Conclusion: Even though the definition of hypertension in still arbitrary in infants, the measurement of blood pressure is necessary when steroid therapy is given for the treatment of hemangiomas. Blood pressure measurement can be difficult in very young children and overestimation is frequent if an inadequate device is used. The exact place of cardiac ultrasound remains to be defined in the management of alarming hemangiomas.

Purpose: Retrospective analysis of the morphologic and hemodynamic characteristics of hemangiomas in infants provided by color Doppler sonography., Materials and Methods: 94 hemangiomas were studied in 87 children separated into four classes of age (0-3 months, 3-6 months, 6-12 months, > 12 months). Eleven were followed with several examinations. Echogenicity, compared to normal subcutaneous tissues, and degree of vascularization were assessed qualitatively. Resistive index (RI) was measured in 78 cases., Results: All lesions presented as vascularized solid masses: 63% were hypoechoic, 16% hyperechoic and 21% mixed. All hypoechoic and mixed lesions showed higher vascularity than hyperechoic ones. Hyperechoic hemanigomas were more frequent in the fourth class of age. Mean resistive index was significantly higher in the first (0.61 +/- 0.14) and the fourth (0.6 +/- 0.14) classes of age than in the second (0.51 +/- 0.12) (p = 0.01 and < 0.03, respectively), and higher in the hyperechoic group (0.7 +/- 0.13) than in the hypoechoic group (0.53 +/- 0.11), (p < 0.01). Seven of 11 cases moved from hypoechoic to hyperechoic or mixed. Increase of resistive index with age was noted in 9/11 cases., Conclusions: Superficial hemangiomas have typical but variable gray-scale, spectral and color flow sonographic patterns. These fluctuations are probably related to phases of evolution.

We report a case of generalized infantile myofibromatosis with favorable outcome despite systemic involvement. Elevated urinary bFGF levels during the active phase of the disease suggested an angiogenic stimulation in the pathogenesis of myofibromatosis.

Introduction: High-dose corticosteroids are the primary means of controlling alarming hemangiomas. However, only 2/3 of these life-threatening hemangiomas regress or are stabilized with corticosteroids: and for others there is no regularly safe and effective treatment. Contradictory publications have been reported about the efficacy of interferon (INF) alpha in hemangiomas, we report our experience concerning the management of 7 cases., Patients and Methods: Seven infants have been treated with INF alpha-2b in our Pediatric Dermatology Unit. All hemangiomas were corticosteroid resistant. Hemangiomas were located on head and neck in 6 cases and on lower limb in one case in association with platelet trapping syndrome. Mean age at beginning of treatment was 7.5 months and mean duration of treatment was 5 months. INF alpha-2b was given daily in subcutaneous injections of 3 millions units per square meter of body surface area., Results: After one month of treatment, 2 cases of facial hemangiomas showed a dramatic improvement, and INF alpha-2b was maintained for one year. One case was stabilized, but INF was ineffective in 3 cases after 2 months of treatment (the child with platelet trapping syndrome died at 4 months of age). The treatment had to be stopped in one case because of hepatitis. No long term side effects were noted with a mean follow-up of 27 months., Conclusion: INF alpha can be an interesting alternative therapy for infantile hemangiomas. However, only a minority of patients can be considered as excellent responders at current dosages and long term secondary effects cannot be excluded.