{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:56:57Z","timestamp":1788339417574,"version":"build-2803163510"},"reference-count":30,"publisher":"MJS Publishing, Medical Journals Sweden AB","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Derm Venereol"],"abstract":"<jats:p>Propranolol at 3 mg\/kg\/day is considered the gold standard for treating infantile haemangiomas. Nevertheless, the management of propranolol-resistant infantile haemangiomas (PRIH) remains challenging. This national multicentre retrospective observational study includes all PRIHs who received propranolol &gt;\u20093 mg\/kg\/day. The study aims to investigate the pattern of PRIHs, assess the effects and tolerance of a higher dose, and identify predictive factors for response to this increased dosage. Fifteen PRIHs were included (prevalence 0.45%), mainly females, and most presented with a large lesion. Three distinct patterns of PRIH were identified: facial segmental lesions (47%), facial localized lesions with a subcutaneous component (40%), and body-localized mixed and ulcerated lesions (13%). Six PRIH (40%) responded to the higher dose (from 3.75 to 4 mg\/kg\/day). Three predictive factors were significantly associated with a good response: IGIc-IH1 at the end of 3 mg\/kg\/day regimen (OR\u2009=\u200922.9, 95% CI [1.2\u20131844.1]), a duration of 3.5 months or more at 3 mg\/kg\/day (OR\u2009=\u200917.5, 95% CI [1.22\u2013250.37]), and 7 months or more at &gt;\u20093 mg\/kg\/day (OR\u2009=\u200917.5, 95% CI [1.22\u2013250.37]). Tolerance was generally good, although one patient experienced severe hypotension during dose escalation. Propranolol doses higher than 3 mg\/kg\/day may therefore be considered a potential treatment option for PRIHs.<\/jats:p>","DOI":"10.2340\/actadv.v106.43152","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:14:50Z","timestamp":1769156090000},"page":"adv43152","source":"Crossref","is-referenced-by-count":1,"title":["Higher Doses of Oral Propranolol for Resistant Infantile Haemangio\u00admas"],"prefix":"10.2340","volume":"106","author":[{"given":"Isabelle","family":"Dreyfus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charl\u00e8ne","family":"D\u00e9nos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Boccara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Barbarot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Gagey-Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Maruani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Miquel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Droitcourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Bigorre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovic","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Leaut\u00e9-Labr\u00e8ze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Mazereeuw-Hautier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1183","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"139455","doi-asserted-by":"crossref","unstructured":"L\u00e9aut\u00e9-Labr\u00e8ze C, Harper JI, Hoeger PH. Infantile haemangioma. Lancet 2017; 390: 85\u201394.","DOI":"10.1016\/S0140-6736(16)00645-0"},{"key":"139456","doi-asserted-by":"crossref","unstructured":"Jacobs AH, Walton RG. The incidence of birthmarks in the neonate. Pediatrics 1976; 58: 218\u2013222.","DOI":"10.1542\/peds.58.2.218"},{"key":"139457","doi-asserted-by":"crossref","unstructured":"L\u00e9aut\u00e9-Labr\u00e8ze C, Prey S, Ezzedine K. Infantile haemangioma: part I. Pathophysiology, epidemiology, clinical features, life cycle and associated structural abnormalities. J Eur Acad Dermatol Venereol 2011; 25: 1245\u20131253.","DOI":"10.1111\/j.1468-3083.2011.04102.x"},{"key":"139458","doi-asserted-by":"crossref","unstructured":"Chang LC, Haggstrom AN, Drolet BA, Baselga E, Chamlin SL, Garzon MC, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008; 122: 360\u2013367.","DOI":"10.1542\/peds.2007-2767"},{"key":"139459","doi-asserted-by":"crossref","unstructured":"Jacobs AH. Strawberry hemangiomas; the natural history of the untreated Lesion. Calif Med 1957; 86: 8\u201310.","DOI":"10.1097\/00006534-195705000-00023"},{"key":"139460","doi-asserted-by":"crossref","unstructured":"Baselga E, Roe E, Coulie J, Mu\u00f1oz FZ, Boon LM, McCuaig C, et al. Risk factors for degree and type of sequelae after involution of untreated hemangiomas of Infancy. JAMA Dermatol 2016; 152: 1239\u20131243.","DOI":"10.1001\/jamadermatol.2016.2905"},{"key":"139461","doi-asserted-by":"crossref","unstructured":"L\u00e9aut\u00e9-Labr\u00e8ze C, Prey S, Ezzedine K. Infantile haemangioma: Part II. Risks, complications and treatment. J Eur Acad Dermatol Venereol 2011; 25: 1254\u20131260.","DOI":"10.1111\/j.1468-3083.2011.04105.x"},{"key":"139462","doi-asserted-by":"crossref","unstructured":"Hoeger PH, Harper JI, Baselga E, Bonnet D, Boon LM, Atti MCD, et al. Treatment of infantile haemangiomas: recommendations of a European expert group. Eur J Pediatr 2015; 174: 855\u2013865.","DOI":"10.1007\/s00431-015-2570-0"},{"key":"139463","doi-asserted-by":"crossref","unstructured":"Drolet BA, Frommelt PC, Chamlin SL, Haggstrom A, Bauman NM, Chiu YE, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics 2013; 131: 128\u2013140.","DOI":"10.1542\/peds.2012-1691"},{"key":"139464","doi-asserted-by":"crossref","unstructured":"L\u00e9aut\u00e9-Labr\u00e8ze C, de la Roque ED, Hubiche T, Boralevi F, Thambo J-B, Ta\u00efeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358: 2649\u20132651.","DOI":"10.1056\/NEJMc0708819"},{"key":"139465","doi-asserted-by":"crossref","unstructured":"Canadas KT, Baum ED, Lee S, Ostrower ST. Case report: Treatment failure using propranolol for treatment of focal subglottic hemangioma. Int J Pediatr Otorhinolaryngol 2010; 74: 956\u2013958.","DOI":"10.1016\/j.ijporl.2010.05.012"},{"key":"139466","doi-asserted-by":"crossref","unstructured":"Fuchsmann C, Quintal M-C, Giguere C, Ayari-Khalfallah S, Guibaud L, Powell J, et al. Propranolol as first-line treatment of head and neck hemangiomas. Arch Otolaryngol Head Neck Surg 2011; 137: 471\u2013478.","DOI":"10.1001\/archoto.2011.55"},{"key":"139467","doi-asserted-by":"crossref","unstructured":"Chang L, Chen H, Yang X, Jin Y, Ma G, Lin X. Intralesional bleomycin injection for propranolol-resistant hemangiomas. J Craniofac Surg 2018; 29: e128\u2013e130.","DOI":"10.1097\/SCS.0000000000004152"},{"key":"139468","doi-asserted-by":"crossref","unstructured":"Causs\u00e9 S, Aubert H, Saint-Jean M, Puzenat E, Bursztejn A-C, Eschard C, et al. Propranolol-resistant infantile haemangiomas. Br J Dermatol 2013; 169: 125\u2013129.","DOI":"10.1111\/bjd.12417"},{"key":"139469","doi-asserted-by":"crossref","unstructured":"Gnanasakthy A, Barrett A, Norcross L, D\u2019Alessio D, DeMuro Romano C. Use of patient and investigator global impression scales: a review of food and drug administration-approved labeling, 2009 to 2019. Value Health 2021; 24: 1016\u20131023.","DOI":"10.1016\/j.jval.2021.01.005"},{"key":"139470","doi-asserted-by":"crossref","unstructured":"L\u00e9aute-Labr\u00e8ze C, Boccara O, Degrugillier-Chopinet C, Mazereeuw-Hautier J, Prey S, Lebb\u00e9 G, et al. Safety of oral propranolol for the treatment of infantile hemangioma: a systematic review. Pediatrics 2016; 138: e20160353.","DOI":"10.1542\/peds.2016-0353"},{"key":"139471","doi-asserted-by":"crossref","unstructured":"Onnis G, Dreyfus I, Mazereeuw-Hautier J. Factors associated with delayed referral for infantile hemangiomas necessitating propranolol. J Eur Acad Dermatol Venereol 2018; 32: 1584\u20131588.","DOI":"10.1111\/jdv.14842"},{"key":"139472","doi-asserted-by":"crossref","unstructured":"Qiu T, Yang K, Dai S, Chen S, Ji Y. Clinical features of segmental infantile hemangioma: a prospective study. Ther Clin Risk Manag 2021; 17: 119\u2013125.","DOI":"10.2147\/TCRM.S291059"},{"key":"139473","doi-asserted-by":"crossref","unstructured":"D\u00e1vila-Osorio VL, Iznardo H, Ro\u00e9 E, Puig L, Baselga E. Propranolol-resistant infantile hemangioma successfully treated with sirolimus. Pediatr Dermatol 2020; 37: 684\u2013686.","DOI":"10.1111\/pde.14163"},{"key":"139474","doi-asserted-by":"crossref","unstructured":"Pratico AD, Caraci F, Pavone P, Falsaperla R, Drago F, Ruggieri M. Propranolol: effectiveness and failure in infantile cutaneous hemangiomas. Drug Saf Case Rep 2015; 2: 6.","DOI":"10.1007\/s40800-015-0009-1"},{"key":"139475","doi-asserted-by":"crossref","unstructured":"Ritter MR, Moreno SK, Dorrell MI, Rubens J, Ney J, Friedlander DF, et al. Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution. Lymphat Res Biol 2003;1: 291\u2013299.","DOI":"10.1089\/153968503322758094"},{"key":"139476","doi-asserted-by":"crossref","unstructured":"Kaulanjan-Checkmodine P, Oucherif S, Prey S, Gontier E, Lacomme S, Loot M, et al. Is infantile hemangioma a neuroendocrine tumor? Int J Mol Sci 2022; 23: 5140.","DOI":"10.3390\/ijms23095140"},{"key":"139477","doi-asserted-by":"crossref","unstructured":"Zhou HH, Koshakji RP, Silberstein DJ, Wilkinson GR, Wood AJ. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites. N Engl J Med 1989; 320: 565\u2013570.","DOI":"10.1056\/NEJM198903023200905"},{"key":"139478","unstructured":"Ma X, ZhaoT, Ouyang T, Xin S, Ma Y, Chang M. Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells. Int J Clin Exp Pathol 2014; 7: 3809\u20133817."},{"key":"139479","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez Faith E, Shah S, Witman PM, Harfmann K, Bradley F, Blei F, et al. Clinical features, prognostic factors, and treatment interventions for ulceration in patients with infantile hemangioma. JAMA Dermatol 2021; 157: 566\u2013572.","DOI":"10.1001\/jamadermatol.2021.0469"},{"key":"139480","doi-asserted-by":"crossref","unstructured":"Meyer-Mueller C, Nicholson C, Polcari I, Boull C, Maguiness S. Worsening ulceration of infantile hemangioma after initiation or escalation of propranolol. Pediatr Dermatol 2022; 39: 255\u2013259.","DOI":"10.1111\/pde.14933"},{"key":"139481","doi-asserted-by":"crossref","unstructured":"Chen T, Gudipudi R, Nguyen SA, Carroll W, Clemmens C. Should propranolol remain the gold standard for treatment of infantile hemangioma? A systematic review and meta-analysis of propranolol versus atenolol. Ann Otol Rhinol Laryngol 2023; 132: 332\u2013340.","DOI":"10.1177\/00034894221089758"},{"key":"139482","doi-asserted-by":"crossref","unstructured":"Warren D, Diaz L, Levy M. Diffuse hepatic hemangiomas successfully treated using sirolimus and high-dose propranolol. Pediatr Dermatol 2017; 34: e286\u2013e287.","DOI":"10.1111\/pde.13219"},{"key":"139483","doi-asserted-by":"crossref","unstructured":"Kaylani S, Theos AJ, Pressey JG. Treatment of infantile hemangiomas with sirolimus in a patient with PHACE syndrome. Pediatr Dermatol 2013; 30: e194\u2013e197.","DOI":"10.1111\/pde.12023"},{"key":"139484","doi-asserted-by":"crossref","unstructured":"Greenberger S, Yuan S, Walsh LA, Boscolo E, Kang KT, Matthews B, et al. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol 2011; 131: 2467\u20132476.","DOI":"10.1038\/jid.2011.300"}],"container-title":["Acta Dermato-Venereologica"],"original-title":[],"link":[{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/download\/43152\/52643","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/download\/43152\/52643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:14:53Z","timestamp":1769156093000},"score":1,"resource":{"primary":{"URL":"https:\/\/medicaljournalssweden.se\/actadv\/article\/view\/43152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":30,"URL":"https:\/\/doi.org\/10.2340\/actadv.v106.43152","relation":{},"ISSN":["1651-2057","0001-5555"],"issn-type":[{"value":"1651-2057","type":"electronic"},{"value":"0001-5555","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}