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      Efficacious Healing of Ulcerated Infantile Hemangiomas Using Topical Timolol

      case-report
      , MD *† , , MD, MEng *‡ ,
      Plastic and Reconstructive Surgery Global Open
      Wolters Kluwer Health

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          Summary:

          Infantile hemangiomas (IHs) are the most common benign pediatric soft-tissue tumors. Ulceration—the most frequent complication of IH—tends to heal poorly and is associated with pain, bleeding, infection, and scarring. Mainstay treatment modalities include propranolol (β-blocker) and corticosteroids, whose effectiveness is countered by a need for long-term medication and risk of systemic adverse effects and ulcer recurrence. A 3-month-old infant presented to us with a large, medial thigh-ulcerated IH that progressed despite 2 prior months of dressings and topical antimicrobials. Topical timolol 0.5% thrice daily was initiated, and significant healing was evident at 1 week, with complete healing at 1 month. Timolol was stopped after 3 months, and at 18 months after cessation of timolol, there was no ulcer recurrence. This novel therapy for ulcerated IH seems to have many advantages such as rapid efficacy with easy application, no systemic adverse effects and no long-term recurrence, and current literature describing similar advantages justifies the use of this treatment modality in infants.

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          Most cited references21

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

          Infantile haemangiomas (IH) are the most common benign tumours of infancy. Although most IH are innocuous and 85-90% regress spontaneously, some may become life- or function-threatening and require immediate treatment. Previous standard therapeutic options include physical measures (laser surgery, cryosurgery) and systemic corticosteroids, in severe cases also vincristine, alpha-interferon or cyclophosphamide, all bearing the risk of serious side-effects. Oral propranolol is a very recent therapeutic option for complicated IH with impressive efficacy and generally good tolerance. The effects of propranolol on IH were discovered by chance, and very little is known about its mechanisms of action in IH. Here we present a summary of current knowledge of how propranolol interferes with endothelial cells, vascular tone, angiogenesis and apoptosis. Early, intermediate and long-term effects of propranolol on IH can be attributed to three different pharmacological targets. Early effects (brightening of the haemangioma surface within 1-3 days after start of therapy) are attributable to vasoconstriction due to decreased release of nitric oxide. Intermediate effects are due to the blocking of proangiogenic signals (vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2/9) and result in growth arrest. Long-term effects of propranolol are characterized by induction of apoptosis in proliferating endothelial cells, and result in tumour regression.
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            Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study.

            Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta-blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel-forming solution and had photographic documentation of the IH and at least one follow-up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel-forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.
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              Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution.

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                Author and article information

                Journal
                Plast Reconstr Surg Glob Open
                Plast Reconstr Surg Glob Open
                GOX
                Plastic and Reconstructive Surgery Global Open
                Wolters Kluwer Health
                2169-7574
                February 2016
                16 February 2016
                : 4
                : 2
                : e621
                Affiliations
                From the [* ]Department of Plastic & Reconstructive Surgery, Craniofacial Research Center, Craniofacial Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan; []Department of Chemical and Materials Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan; and []Department of Plastic, Reconstructive, and Aesthetic Surgery, KK Women’s and Children’s Hospital, Singapore, Singapore.
                Author notes
                Gavin Chun-Wui Kang, MD, MEng, Plastic and Reconstructive Surgery, Department of Plastic & Reconstructive Surgery, Craniofacial Research Center, Craniofacial Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, E-mail: gavinkangcw@ 123456yahoo.com
                Article
                00005
                10.1097/GOX.0000000000000605
                4778892
                27014550
                b6d64674-9f37-4fb7-bc3e-8773be9b88c4
                Copyright © 2016 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                : 6 October 2015
                : 30 December 2015
                Categories
                Case Report
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