Expression of components of the renin–angiotensin system in proliferating infantile haemangioma may account for the propranolol-induced accelerated involution

Itinteang, Tinte; Brasch, Helen D.; Tan, Swee T.; Day, Darren J.

doi:10.1016/j.bjps.2010.08.039

Cited by 156 publications

(154 citation statements)

References 26 publications

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“…Both actions result in diminished production of angiotensin 2 and a subsequent regression of IH. [25] Sinaiko et al found elevated levels of renin in children treated with ACE-inhibitors, suggesting that suppression of renin by β-blockers in addition to ACEinhibition creates an even larger effect on IH regression. [25,38] No further evidence in literature could be found for this therapy.…”

Section: Ace-inhibitorsmentioning

confidence: 99%

“…[25] Sinaiko et al found elevated levels of renin in children treated with ACE-inhibitors, suggesting that suppression of renin by β-blockers in addition to ACEinhibition creates an even larger effect on IH regression. [25,38] No further evidence in literature could be found for this therapy. Adverse effects in this overview came from one study with eight patients showing a transient mild creatinine elevation in the first week of treatment in one of the patients.…”

Section: Ace-inhibitorsmentioning

confidence: 99%

“…The mechanism of action of propranolol in IH is not yet completely understood, but it is thought to originate from several effects, like vasoconstriction, [2,15] inhibition of angiogenesis, [16][17][18][19][20][21][22][23] stimulation of apoptosis [24] and inhibition of the reninangiotensin system (RAS). [25,26] IL: intralesional; IV: intravenous; MESNA: sodium-2-mercaptoethane sulfonate. and inertia.…”

Section: Propranololmentioning

confidence: 99%

“…[25] As the kidneys predominantly express β-1 receptors, the renin-angiotensin-aldosterone system (RAAS) is most likely one of the missing links in understanding the working mechanism of both β-blockers and ACE inhibitors in the treatment of IH. [27] Atenolol is a hydrophilic β-blocker, acting on β-1 receptors with a proven efficacy in the treatment of IH.…”

Section: Atenololmentioning

confidence: 99%

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Treatment of infantile hemangiomas: therapeutic options in regard to side effects and adverse events – a review of the literature

Raphaël

Breur

Vlasveld

et al. 2016

Expert Opinion on Drug Safety

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Introduction: While options for treatment strategies for infantile hemangiomas (IH) are numerous, evidence-based information about agents, optimal dosage, adverse effects, treatment modality, pretreatment and treatment strategies remain limited. Areas covered: To evaluate side effects and adverse events of medical treatment in children with infantile hemangioma, a comprehensive review of the literature was performed to provide information for daily practice. In total 254 studies were retrieved from medical databases and comprised 10,022 patients divided into 5 different treatment groups. Information about working mechanism, side effects and adverse events of therapies used as a single agent for IH are discussed and evaluated according to information from pharmacotherapeutic databases. Randomized controlled trials have only scarcely been performed for the many therapeutic options reported for IH. Short-and long-term side effects and adverse events, have not been systematically studied. Subsequently information about the medical treatment options and pharmacotheraputic databases for therapy in children with IH are incomplete. Expert opinion: From the many therapeutic options, propranolol is the first-line approach for IH, predominantly based on clinical observation, efficacy and tolerability in the short-term. The unsolved ravels of possible short and long-term adverse events of propranolol used during early developmental stages of children need thorough review.

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Section: Ace-inhibitorsmentioning

confidence: 99%

Section: Ace-inhibitorsmentioning

confidence: 99%

Section: Propranololmentioning

confidence: 99%

Section: Atenololmentioning

confidence: 99%

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Treatment of infantile hemangiomas: therapeutic options in regard to side effects and adverse events – a review of the literature

Raphaël

Breur

Vlasveld

et al. 2016

Expert Opinion on Drug Safety

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“…Since then, others have reported similar observations. The exact mechanism of action of propranolol is unclear but may involve microvascular vasoconstriction as well as modulation of angiotensin II (9). Alterations in the cell signalling of angiogenic factors such as vascular endothelial growth factor, basic fibroblast growth factor and metalloproteinases, as well as early apoptosis of endothelial cells, may also be involved (7,(10)(11)(12).…”

mentioning

confidence: 99%

Beta-blockers for the treatment of problematic hemangiomas

et al. 2013

Canadian Journal of Plastic Surgery

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Objective To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas. Methods A retrospective review of patients with hemangiomas presenting to the Alberta Children's Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy. Results Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%). Conclusions Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment.

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