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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 | | | | | | | | | | | Study | Cases | Location | Previous Therapy | Dose (mg/kg/d) | Duration | Response Rate | Measure of Regression | Complications (No. of Patients, %) | Level
of evidence | | Blei and Chianese | 30 | 22 facial
5 subglottic
3 extremities | none | 2-4 | NR | 25% | 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 ] | 60 | 20 orbital
6 subglottic
34 facial | none | 3-5 | 2-3 months | 93% | 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
] | 62 | 50 cervicofacial, 5 subglottic
3 thoracic
1 hepatic
1 perinieal
2 upper extremity | none | 2-3 | 2 weeks | NR | Questionnaire | Moon 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] | 1127 | 1058 head and neck
69 trunk | none | 1-2 | NR | 89% | 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] | 1 | Large gluteal Haemangioma | None | 1 | 3 weeks | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | NR | 5 | | Chen et al] | 155 | Head and neck | None | 0.1-3ml (10 mg/ml/ x4 injections) | 5 months | 60% | visual appearance of lesion. (decrease of at least 50% of volume) | cushingoid appearance (2,1.2%), cutaneous atrophy (5, | 3 | | Chowdri et al[37] | 74 | 48 head and neck, 11 trunk, 15 limbs | None | 0.5-6 ,l (10 mg/ml X 1-7 injections) | 3-4 months | 43% | Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% ) | cushingoid appearance (2, 2.7%) | 3 | | Iwanaka et al[38] | 5 | Eyelid and orbit | None | 2-3 mg/kg/d ( oral) , 40mg triamcinolon + 8 mg | oral steroids: 1 week, injections:2-3 months | 40% | visual appearance of lesion. (decrease of at least 75% of volume) | NR | 4 | | Kushner] | 25 | Periorbital | None | 40 mg traiamcinolone + 6 mg betamethasone X 2 injections | 3-4 weeks | 84% | Marked- >80% regression, Moderate- 20-80%, Minimal- <20% regression | NR | 3 | | Prasetyono et al] | 749 | Head and neck | unsuccessful systemic steroid or laser treatment | 1-2 ml triamcinolone 5% X 3 injections on average | 10-15 weeks | 71% | 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] | 16 | 14 head and neck, 2 upper extremity | None | 2.5 | 3 months | 50% | visual appearance of lesion. (decrease of at least 30% of volume) | lymphocyte decrease (16, 100%), growth retardation | 2 | | Zhou et al[40] | 23 | NA | NA | 3-5 | 3 months | 87% | Excellent (>75% regression ) Good (50-75% regression ) Fair (25-50%) Poor (<25% ) | cushingoid appearance (8, 34%), poor appetite (5, 21%) | 3 | | Chantharatanapiboon[8] | 160 | 19 upper extremity, 7 lower extremity, 134 head and neck | None | 1-2 mg/kg triamcinolone X 5 injections | 4-12 weeks | 90% | NA | NR | 3 | | Rossler et al[41] | 38 | 28 heard and neck, 3 upper extremity, 4 trunk, 1 perineal, 2 Visceral | previous laser therapy | 2 | 4 months | 86% | 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] | 67 | Parotid | None | 2-3 | 9 months | 83% | visual appearance of lesion. Regression, stabilization or no response. | NR | 3 | | Al-Sebeih et al] | 14 | Subglottic | None | 0.5-2 | 9 months | 90% | visual appearance of lesion by bronchoscope. (decrease of at least 50% of volume) | cushingoid face (1, 7%) | 3 | | Narcy et al] | 21 | Subglottic | None | 2 | 22 days | 33% | visual appearance of lesion by bronchoscope. (decrease of at least 50% of volume) | NR | 3 | | | | | | | | | | |
Table 2. Comparison of eleven studies using oral Propranolol for treatment of haemangiomas
| | | | | | | | | | | | | | Study | Cases | Location | Previous Therapy | Dose (mg/kg/d) | Duration of Therapy | Response Rate | Measure of Regression | Level of evidence | Complications
(No. of Patients, %) | | Leaute-Labreze [1] | 11 | 10 facial
1 Forearm | 4 out of 11 patients received | 2 | NR | Facial 100%
Forearm 100% | Visual appearance of lesion. (Significant decrease in pigmentation and size) | 4 | NR | | Theletsane ] | 1 | Facial
Oropharynx
Larynx
PHACES syndrome | High dose steroid response | 2 | NR | 100% | Visual appearance of lesion. (Significant decrease in pigmentation and size) | 5 | NR | | Itani and Fakih | 1 | Upper Eyelid | NR | 2 | NR | 100% | Visual appearance of lesion. (Significant decrease in pigmentation and size. Decreased ocular occlusion) | 5 | NR | | Bigorre ] | 4 | 3 facial (parotideal, hemifacial)
1 perineal | Steroids, no response | 10 (Acebutolo) | 2 Months | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size. Decreased ocular occlusion) | 4 | NR | Denoyelle
[19] | 2 | Subglottic | Vincristine and corticosteroid, no response | NR | NR | 100% | Endoscopy ( decreased subglottic stenosis) | 4 | NR | | Sanchez Perez] | 1 | Facial | NR | 2 | 9 Months | 100% | Visual appearance of lesion. (Significant decrease in pigmentation and size) | 5 | NR | | Buckmiller[11] | 32 | 22 Facial
10 Trunk/Extremity | failed response to: intralesional steroid, debulking with CO2 laser, and vincristine | 2 | NR | 50% | photograph analysis and parent questionnaire (16 excellent responders, no follow-up needed)(15 required follow up) (1 had no response) | 3 | Somnolence (6, 27.3%), Gastroesophageal reflux (2,9.1%), Allergic rash (1, 4.5%), Respiratory syncitial virus exacerbation (1, 4.5%) | Bonifazi
[47] | 11 | 5 Nose, Lip, Forehead, Oral cavity, Cheek
6 parotideal, nipple ankle, nose, parotideal, hand and forearm, metameric | NR | 2
1%topical | NR | 100% | Visual appearance of lesion. (Significant decrease in pigmentation and size) | 4 | NR | | Zimmerman[10] | 1 | Parotideal | Steroid, No response | 2 | 4 Months | 100% | visual appearance of lesion. "nearby complete regression" | 5 | NR | | Sans] | 32 | face, forearm, thorax, neck, parotideal | 13 out of 32 patients received and failed to respond to steroids | 2 | NR | 100% | visual appearance of lesion (Significant decrease in pigmentation, size, and hardness) Ultrasound (thickness), resistivity index | 3 | NR | | Lawley ] | 2 | Eyelid, Hemangiomatosis | steroids and propranolol | 2 | NR | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | 4 | lethargy, hypoglycemia (1, 50%) | | Mahadevan] | 10 | Subglottic | Steroid, no response | 2 | 9-12 months | 100% | Endoscopic (decreased subglottic stenosis) | 3 | NR | | Leboulanger[18] | 14 | Subglottic | Steroid, no response | 2-3 | 6 months | 100% | Endoscopic (decreased subglottic stenosis) | 3 | Asthma (1,7%) | | Mistry] | 1 | Supraglottic | Concurrent Steroid Therapy | 1 | 13 weeks | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | 5 | NR | | Cushung] | 49 | Head and neck | No pervious steroid therapy | 2 | 3-4 months | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | 3 | NR | | Breur] | 1 | Periorbital | Concurrent steroid therapy | 2 | 6 months | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | 5 | Hypoglycemia | | Pavlakovic[15] | 1 | Chest wall | No pervious steroid therapy | 2 | 5 months | 100% | visual appearance of lesion. (Significant decrease in pigmentation and size) | 5 | Hyperkalemia | | Holland[16] | 3 | Eyelid (1), Nasal tip (2) | No pervious steroid therapy | 1-2 | 3 weeks-4 months | NR | NR | 4 | Hypoglycemia | | Sans] | 32 | Face, Forearm, thorax, neck, Parotid | 13 out of 32 patients received and failed to respond to steroids | 2 | NR | 100% | visual appearance of lesion (Significant decrease in pigmentation, size, and hardness) Ultrasound (thickness), resistivity index | 3 | NR |
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