Infantile Hemangiomas: Medicine, Surgery or Laser
Ilona Frieden M.D. Professor of Dermatology and Pediatrics University of California San Francisco
Consultant for Pierre Fabre Dermatology
Why do we treat a condition that will go away on its own?
Benign and “Go Away” BUT…
Spontaneous involution Most IH need no Rx
but… Minority leave
permanent skin changes Smaller minority cause
medical morbidities How to pick out the
“bad actors”
Game Changer Beta-Blockers for IH
Léauté-Labrèze C et al
June 12, 2008
Retrospective Paired Comparison Propranolol vs Steroid
12 patients matched Rx propranolol vs Steroid “controls” for site, age, subtype
Response graded via photographs At 6 months, 12/12 in propranolol group
showed G to E response vs. 9/12 in the prednisone group with S to M response.
Propranolol superior to steroid in inducing more-rapid and greater response
Bertrand J et al. Pediatr Dermatol. 2011;28:649-54.
Rest of Talk
When do you need Medicine Surgery or Laser?
Beta-blockers –systemic and topical
Lasers – early vs late Surgery – early vs late
Clinically Heterogeneous When do we need to worry?
How to tell a worrisome IH from a banal one?
If treatment is needed…Which Rx?
Most common reason for Rx: IH living in “bad neighborhood”
LOCATION: High-Risk for Disfigurement
Nasal tip Perioral Glabella Eyebrow Central face
Haggstrom A et al. Arch Dermatol. 2012 ;148:197-202.
Medically Threatening: Location and Number
Periocular Beard area: Risk of airway Multiple (>5): higher risk of liver
hemangiomas Extracutaneous structural anomalies
Large facial: Risk of PHACE syndrome Lumbosacral: Risk of spinal dysraphism,
genitourinary anomalies
Most common sequella: Permanent Skin changes
Residual skin changes
Residual lesions in referral setting are common
Superficial IH more likely to leave residual skin changes than deep IH
Permanent skin changes in ~ one-third in untreated referral cohort
Bauland CG et al. Plast Reconstr Surg 2011;127:1643
Treatment Options
Serial observation Systemic therapies (propranolol,
steroids) Topical/local therapies (laser; timolol) Surgery – early or late
Propranolol 5 years later More than 275 articles published including 1
RCT, 2 systematic reviews >1000 patient patients reported 90+% response rate AEs: Cold hands/feet, sleep disturbances Most serious side effect: hypoglycemia Cardiovascular effects not major limitation Hogeling et al. Pediatrics 2011;128:e259 Izadpanah A et al. Plast Reconstr Surg. 2013;131:601-13 Marqueling A et al. Pediatr Dermatol 2013;30:182-91
Multicenter RCT (Pierre Fabre) 460 infants Placebo vs 1mg/k vs 3 mg/K 3 months versus 6 months of treatment Primary endpoint: Complete or Near-
Complete Resolution
Safety data • No unexpected safety signal related to
propranolol
• No obvious dose dependence for adverse effects except for wheezing and diarrhea - without severe consequences for the patients
• Very few cardiovascular effects with no obvious dose dependence in the tested range
What to Tell Parents
Martin K et.al. Pediatr Dermatol. 2013;30:155-9.
Does Propranolol Always Work?
Multicenter observational study in France 2011
1130 patients treated with propranolol for infantile hemangioma, 10 (0.9%) had propranolol-resistant IHs.
Hemangioma propranolol-resistance was rare but observed at all ages during early childhood and at any proliferation stage.
Causse et al. Br J Dermatol. 2013 May 9. [Epub ahead]
Rebound/Relapse Retrospective study of 158 infants 118 no relapse 40 had relapse (25%)
Minor relapse in 21/40 Major relapse in 19/40 (12%)
Risk factors with multivariate analysis were segmental morphology (10 x risk) and deeper lesions
Ahogo et al. Br J Dermatol 2013 Online
Timolol (and potentially other topical Beta-blockers) for IH
Timolol: The Evidence July 2013
17 original studies (case reports or series) ~250 patients Minimal to no toxicity reported Results (with pre-selection) good to
excellent “Enthusiastic tone” not just “worth a try”
Occasionally results are better than expected (thin skin sites)
Before and after 4 mos Fernández-Ballesteros et al. Actas Dermosifiliogr. 2012 ;103:444-6
Ni et al Arch Ophthalmol. 2011;129:373-379
Timolol RCT
41 infants randomized to Timolol 0.5 gel or placebo gel for 24 weeks: 1 gtt BID
15 in Rx group and 17 in placebo group completed study.
Significant color change at W 24 in Rx group (p=0.003) and smaller proportionate volume change
No difference HR in 2 groups Chan et al. Pediatrics 2013;131:1–9
Timolol: Note of Caution
Systemic absorption possible ~10x more potent than propranolol Caution for ulcerated or large areas Seems very safe if limited to 1 gtt BID-TID Can measure HR; look for “by-stander”
effect on other hemangiomas McMahon P et al. Pediatr Dermatol 2012;29:127-30
Other Options: Pulsed Dye Laser Multimodal Rx Early Surgery
Laser – When and Which
Early - ? Can you decrease propranolol use Later to “mop up” – could be >6 mos or later Fractionated laser for textural changes
Reddy KK et al. Dermatol Surg. 2013;39:923-33. Brightman LA et al. Arch Dermatol. 2012;148:1294-8
Copyright © 2012 American Medical Association. All rights reserved."
From: Ablative Fractional Resurfacing for Involuted Hemangioma Residuum!
Arch Dermatol. 2012;148(11):1294-1298. doi:10.1001/archdermatol.2012.2346"
."
What about timing of involution? 81 patients - 88%
needed reconstive surgery for residual deformity.
Involution ceased at a median age of 36 months
92% of IH completed involution by 4 years
Couto et al. Plast Reconstr Surg. Online early 5/9/12
Reevaluation at age 3 to 4 years
“If there is a problem, we’ll take care of it before Kindergarten”
Can gauge whether permanent skin changes more easily
This timing also fits with knowledge of cognitive development
Two Pearls
You have seen a child and diagnosed a low-risk hemangioma…
Parents may still be worried
Second Pearl: Timing
If you need to treat, early is better!
The hemangioma time clock: Growth is the “4th dimension” of IH
80% completed by 5 months
Chang et al. Pediatrics 2008;122:360-7
Looking at very early growth Birth 10 days 5 weeks
7 weeks 8weeks 3 months
Early Growth: Most rapid between 5 and 7 weeks
Tollefson MM, Frieden IJ Pediatrics. 2012 ;130:e314-20.
Need for Paradigm Shift Triage and Follow-up