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Role of Propranolol and Corticosteroid in treatment of Haemangiomas; a Systematic Review
Arash Izadpanah, MD, CM, Ali Izadpanah, MD,CM, MSc, Jonathan Kavensky, BSc, Karl Schwarz, MD, FRCSC, MSc.
McGill University, Westmount, QC, Canada.

Role of Propranolol and Corticosteroid in treatment of Haemangiomas; a Systematic Review
Arash Izadpanah, MD, CM, Ali Izadpanah, MD, CM, MSc, Jonathan Kanevsky, BSc, Karl Schwarz, MD, FRCSC
McGill University Health Centre, Montreal, Quebec, Canada
Abstract
Purpose
Infantile haemangiomas are benign vascular neoplasms that can cause numerous functional or cosmetic problems. There has been developing interest in the use of propranolol in the treatment of infantile haemangioma as both first line and concurrent therapy with corticosteroids. We reviewed the roles of propranolol and corticosteroids in the treatment of haemangiomas.
Method
A literature review was performed for all articles published for haemangioma treatment using corticosteroids and Propranolol therapy from 1965 to May 2011. Articles were reviewed for reports of clinical cases, reported side effects, doses, duration of treatment, number of patients and response rate to treatment.
Results
Seven hundred and forty five studies were identified, out of which only 38 studies met our inclusion criteria comprising 2,697 patients being treated with local or oral steroids (19 studies) and 19 studies comprising 177 patients being treated with propranolol, out of which 82 (46.3%) patients had received prior corticosteroid therapy. Overall response rate to corticosteroids was 76.1% compared to 98.9% for all patients treated with Propranolol.
Statistical analysis using Chi-square demonstrates the isolated systemic Propranolol (91.0% resolution rate) administration to be superior to both oral corticosteroids therapy (1,219 out of 1,442 patients; 84.5% resolution rate) and local administration of corticosteroids (834 out of 1255 patients; 66.4% resolution rate) (p<0.0001) (Table 3).
Conclusion
Propranolol is an emerging therapy for infantile haemangioma with fewer side effects and greater efficacy than corticosteroid therapy. Present systematic review demonstrates that the regression of haemangioma when treated with Propranolol as first line therapy is consistently better than those treated with corticosteroids.
Table 1. Comparison of Twenty-one studies using oral steroid for treatment of haemangiomas
StudyCases Location Previous TherapyDose (mg/kg/d)Duration Response RateMeasure of RegressionComplications (No. of Patients, %)Level
of evidence
Blei and Chianese3022 facial
5 subglottic
3 extremities
none2-4NR25%Visual appearance of lesion. (Significant decrease in pigmentation and size)Altered growth parameters (18, 60%)
Delayed milestones (3, 10%)
Endocrine changes (4, 13%)
Moon facies (7, 23%)
3
Sadan and Wolach ]6020 orbital
6 subglottic
34 facial
none3-52-3 months93%Visual appearance of lesion. Excellent (involution within 1-2 weeks with no regrowth) Good (slower involution with, multiple courses of treatment) Failed (no response to therapy)Moon facies (32, 53%)
Growth retardation (1, 1.6%)
Osteoporosis (1, 1.6%)
3
Boon et al
]
6250 cervicofacial, 5 subglottic
3 thoracic
1 hepatic
1 perinieal
2 upper extremity
none2-32 weeksNRQuestionnaireMoon facies (44, 70%)
Personality changes (18, 29%) Fungal infection (4, 6%)
Growth retardation (22, 35%)
Low weight gain (26, 41%)
3
Pandey et al
[2]
11271058 head and neck
69 trunk
none1-2NR89%Excellent (more than 75% regression without any significant scarring) Good (50-75% regression with/without scarring) Poor (25-50% regression with/without scarring) No response (<25% or no regression)Hypertension (50, 4%)
Growth retardation (58, 5%)
Moon facies (58, 5%)
3
Argenta et al]1Large gluteal HaemangiomaNone13 weeks100%visual appearance of lesion. (Significant decrease in pigmentation and size)NR5
Chen et al]155Head and neckNone0.1-3ml (10 mg/ml/ x4 injections)5 months60%visual appearance of lesion. (decrease of at least 50% of volume)cushingoid appearance (2,1.2%), cutaneous atrophy (5,3
Chowdri et al[37]7448 head and neck, 11 trunk, 15 limbsNone0.5-6 ,l (10 mg/ml X 1-7 injections)3-4 months43%Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% )cushingoid appearance (2, 2.7%)3
Iwanaka et al[38]5Eyelid and orbitNone2-3 mg/kg/d ( oral) , 40mg triamcinolon + 8 mgoral steroids: 1 week, injections:2-3 months40%visual appearance of lesion. (decrease of at least 75% of volume)NR4
Kushner]25PeriorbitalNone40 mg traiamcinolone + 6 mg betamethasone X 2 injections3-4 weeks84%Marked- >80% regression, Moderate- 20-80%, Minimal- <20% regressionNR3
Prasetyono et al]749Head and neckunsuccessful systemic steroid or laser treatment1-2 ml triamcinolone 5% X 3 injections on average10-15 weeks71%Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% )failure to thirve 1.7%, injection site ulceration 1.4%2
Kelly et al[39]1614 head and neck, 2 upper extremityNone2.53 months50%visual appearance of lesion. (decrease of at least 30% of volume)lymphocyte decrease (16, 100%), growth retardation2
Zhou et al[40]23NANA3-53 months87%Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% )cushingoid appearance (8, 34%), poor appetite (5, 21%)3
Chantharatanapiboon[8]16019 upper extremity, 7 lower extremity, 134 head and neckNone1-2 mg/kg triamcinolone X 5 injections4-12 weeks90%NANR3
Rossler et al[41]3828 heard and neck, 3 upper extremity, 4 trunk, 1 perineal, 2 Visceralprevious laser therapy24 months86%Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% )behavioural change (6, 25%), growth retardation (3, 8%), hypertension (2, 5%)3
Pope et al [42]10
10
Head and neck
Head and neck
None
None
2 (mg/kg/d) IV pulse of 30 mg/kg/month
IV pulse of 30 mg/kg/month
3 months
3 months
70%
12%
Visual analog scale
Visual analog scale
Hypertensions (4, 20%), abnormal cortisol (16,80%)
Hypertensions (4, 20%), abnormal cortisol (16,80%)
1
Jalil et al]25
25
NR
NR
None
None
2
1-5 mg/kg triamcinolone x 6month
2months
6 months
32%
44%
visual appearance of lesion. (decrease of at least 50% of volume)Overall 20%
Overall 24%
1
Greene et al[43]67ParotidNone2-39 months83%visual appearance of lesion. Regression, stabilization or no response.NR3
Al-Sebeih et al]14SubglotticNone0.5-29 months90%visual appearance of lesion by bronchoscope. (decrease of at least 50% of volume)cushingoid face (1, 7%)3
Narcy et al]21SubglotticNone222 days33%visual appearance of lesion by bronchoscope. (decrease of at least 50% of volume)NR3

Table 2. Comparison of eleven studies using oral Propranolol for treatment of haemangiomas
StudyCasesLocation Previous TherapyDose (mg/kg/d)Duration of TherapyResponse RateMeasure of RegressionLevel of evidenceComplications
(No. of Patients, %)
Leaute-Labreze [1]1110 facial
1 Forearm
4 out of 11 patients received2NRFacial 100%
Forearm 100%
Visual appearance of lesion. (Significant decrease in pigmentation and size)4NR
Theletsane ]1Facial
Oropharynx
Larynx
PHACES syndrome
High dose steroid response2NR100%Visual appearance of lesion. (Significant decrease in pigmentation and size)5NR
Itani and Fakih1Upper EyelidNR2NR100%Visual appearance of lesion. (Significant decrease in pigmentation and size. Decreased ocular occlusion)5NR
Bigorre ]43 facial (parotideal, hemifacial)
1 perineal
Steroids, no response10 (Acebutolo)2 Months100%visual appearance of lesion. (Significant decrease in pigmentation and size. Decreased ocular occlusion)4NR
Denoyelle
[19]
2SubglotticVincristine and corticosteroid, no responseNRNR100%Endoscopy ( decreased subglottic stenosis)4NR
Sanchez Perez]1FacialNR29 Months100%Visual appearance of lesion. (Significant decrease in pigmentation and size)5NR
Buckmiller[11]3222 Facial
10 Trunk/Extremity
failed response to: intralesional steroid, debulking with CO2 laser, and vincristine2NR50%photograph analysis and parent questionnaire (16 excellent responders, no follow-up needed)(15 required follow up) (1 had no response)3Somnolence (6, 27.3%), Gastroesophageal reflux (2,9.1%), Allergic rash (1, 4.5%), Respiratory syncitial virus exacerbation (1, 4.5%)
Bonifazi
[47]
115 Nose, Lip, Forehead, Oral cavity, Cheek
6 parotideal, nipple ankle, nose, parotideal, hand and forearm, metameric
NR2
1%topical
NR100%Visual appearance of lesion. (Significant decrease in pigmentation and size)4NR
Zimmerman[10]1ParotidealSteroid, No response24 Months100%visual appearance of lesion. "nearby complete regression"5NR
Sans]32face, forearm, thorax, neck, parotideal13 out of 32 patients received and failed to respond to steroids2NR100%visual appearance of lesion (Significant decrease in pigmentation, size, and hardness) Ultrasound (thickness), resistivity index3NR
Lawley ]2Eyelid, Hemangiomatosissteroids and propranolol2NR100%visual appearance of lesion. (Significant decrease in pigmentation and size)4lethargy, hypoglycemia (1, 50%)
Mahadevan]10SubglotticSteroid, no response29-12 months100%Endoscopic (decreased subglottic stenosis)3NR
Leboulanger[18]14SubglotticSteroid, no response2-36 months100%Endoscopic (decreased subglottic stenosis)3Asthma (1,7%)
Mistry]1SupraglotticConcurrent Steroid Therapy113 weeks100%visual appearance of lesion. (Significant decrease in pigmentation and size)5NR
Cushung]49Head and neckNo pervious steroid therapy23-4 months100%visual appearance of lesion. (Significant decrease in pigmentation and size)3NR
Breur]1PeriorbitalConcurrent steroid therapy26 months100%visual appearance of lesion. (Significant decrease in pigmentation and size)5Hypoglycemia
Pavlakovic[15]1Chest wallNo pervious steroid therapy25 months100%visual appearance of lesion. (Significant decrease in pigmentation and size)5Hyperkalemia
Holland[16]3Eyelid (1), Nasal tip (2)No pervious steroid therapy1-23 weeks-4 monthsNRNR4Hypoglycemia
Sans]32Face, Forearm, thorax, neck, Parotid13 out of 32 patients received and failed to respond to steroids2NR100%visual appearance of lesion (Significant decrease in pigmentation, size, and hardness) Ultrasound (thickness), resistivity index3NR


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