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