Propranolol, hemangioma

1. 28 May 20151

2. F Thoumazet, CLe´aute´-Labre`ze, J Colin, B Mortemousque
Br J Ophthalmol 2012

3. Introduction
 Most common tumours of infancy.
 They follow a predictable clinical course, beginning
in the first 2weeks of life
 Phases
 proliferative phase ….. lasting for up to 1 year.
 involuting phase ….. Over the next 7 to 10 years
28 May 20153

4.  Outcome
 Disfiguring lesion,
 many do not need to be treated.
 About 20% of haemangiomas are extremely
disfiguring and destructive to normal tissue, and
may even be life-threatening. Such haemangiomas
must be treated.*
*. Frieden IJ. Guidelines of care for hemangiomas of infancy. J Am Acad Dermatol
1997;37:631e7
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5. Treatment options
 Corticosteroids are considered to be first-line therapy
for problematic infantile capillary haemangiomas*
 Other therapeutic options include vincristine and
interferon-a**
 In 2008, Léauté Labrèze et al reported on the
spectacular effect of propranolol therapy on
haemangiomas***
* Bennett ML, Fleischer AB Jr, Chamlin SL, et al. Oral corticosteroid use is effective for cutaneous hemangiomas: an evidence based evaluation. Arch Dermatol
2001;137:120813.
** Ezekowitz RA, Mulliken JB, Folkman J. Interferon alfa2a therapy for life-threatening hemangiomas of infancy. N Engl J Med 1992;326:1456e63.
***Le´aute´-Labre`ze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. New Engl J Med 2008;358:2650e1
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6. METHODS
 An experimental clinical trial was launched in
November 2007 that included children with severe
disfiguring infantile capillary haemangiomas
involving the periocular region.
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7.  All children were given propranolol at a dose of
2mg/kg body weight per day.
 after excluding contra-indications to beta-blocker
therapy (congestive cardiac failure, asthma,
obstructive pulmonary disease).
 3 received both steroids and propranolol
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8. Diagnosis was made by :
 Clinical examination,
 Colour Doppler ultrasound and
 MRI in cases where intraorbital extension was
suspected.
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9. The children were followed at each
examination visit by:
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 general pediatrician,
 pediatric dermatologist,
 ophthalmologist
 radiologist

10. Follow-ups:
 1 week after starting beta-blocker treatment,
 1 month,
 monthly intervals until total regression and after
therapy ended
In some cases with life-threatening haemangiomas,
examination was undertaken every day.
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11. At each visit were performed……
 Fundoscopy,
 Retinoscopy
 Photography
 Visual acuity
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12. The side-effects of beta-blockers were
carefully monitored :
acrocyanosis, pulmonary functions
drowsiness, blood pressure monitoring,
irritability, echocardiography
gastric acid backward flow. rhythm cardiac monitoring
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13. RESULTS:
 Treatment was initiated at ages 1 to 36 (mean 4.9)
months, for a total duration of 3 to 10 (mean 6.8)
months.
 Follow-up was staggered over 6 to 30 months, with
a follow-up period after treatment had been
stopped of up to 25 (mean 14) months.
 Initial follow-up after stopping treatment was
conducted monthly, then every 2 months, and
eventually every 3 months
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14. 28 May 201514

15. We observed a 100% response to
treatment, as follows:
 Clinical regression
 Ultrasonographic regression
 Regression on MRI
28 May 201515

16. Clinical regression:
 flattening of the lesion was noted, with a decrease
in astigmatism for the compressive forms.
 The difference in corneal astigmatism in relation to
the healthy eye after 3 months of treatment
decreased from 3.5 to 0.75 D, which is a reduction of
almost 80% in astigmatism during the first 3months
 A slower regression, more or less complete, leaving
a residual telangiectatic aspect to the skin for
certain deep and extensive forms.
28 May 201516

17. clinical regression after 3.5 months of
systemic propranolol.
photographs of intra-orbital haemangioma: (A) At age 2 months: day 0
propranolol; (B) propranolol only (2 mg/kg per day) at 1 month of treatment
.reduction of astigmatism by 2.75 D; (C) propranolol only at 3.5 months of
treatment- complete regression of astigmatism 28 May 201517

18. Flattening infantile haemangioma after 24 h of systemic propranolol.28 May 201518

19. Ultrasonographic regression:
 with a decrease in lesion thickness ,
 increase in resistance index of blood vessels on
Doppler imaging.
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20. Regression on MRI :
 in certain infants, with minimal residual lesion of the
intraorbital haemangioma after 3months of
treatment.
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21. Intra-orbital haemangioma on MRI: total regression following 3.5
months of systemic propranolol. 28 May 201521

22.  One case was excluded because asthma occurred
during beta-blocker therapy.
 Authors observed some expected side effects such
as acrocyanosis , nightmares, drowsiness, minor
bronchospasm , and a small drop in blood pressure,
which had no clinical repercussions
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23.  Tolerance to treatment was generally good in most
patients, with a slight re-colouring of the
haemangioma upon cessation of therapy in the
deeper forms.
 No recurrence was observed following propranolol
discontinuation , with a follow-up of 14months on
average, and 25months for the longest follow-up.
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24. DISCUSSION
 Infantile haemangiomas are common childhood
vascular tumours, occurring in 1% to 3% of newborns,
even more frequently in premature infants, and in
10% of children by 1 year of age.*
 Infant haemangiomas usually appear in the first
weeks of life, while being occasionally present at
birth, with a preferred location on the head and
neck.
*. Shields CL, Shields JA, Minzter R, et al. Cutaneous capillary hemangiomas of the eyelid, scalp, and digits in
premature triplets. Am J Ophthalmol 2000;129:528e31. 28 May 201524

25.  In the periocular region, these lesions may cause
functional and cosmetic deformities*
 Haemangiomas are clinically diverse, depending on
the location, depth and stage of evolution.
 Beginning as a pale macula in the newborn, the
tumour tends to proliferate, assuming the form of a
bright red, elevated and non-compressible
plaque.**
*. Coats DK, O’Neil JW, D’Elia VJ, et al. SubTenon’s infusion of steroids for treatment of orbital hemangiomas. Ophthalmology 2003;110:1255e9
**. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med 1999;341:173e81 28 May 201525

26.  Haik et al analysed the clinical records of 101 patients
with haemangiomas of the orbit and eyelids. *
 The main signs noted were a subcutaneous or anterior
orbital fullness in 67 patients, a periocular swelling with
superficial strawberry haemangioma in 25 patients, and a
strawberry haemangioma without deep lid orbital
swelling in one patient.
 Proptosis and ocular displacement were common
findings among all patient
*. Haik BG, Jakobiec FA, Ellsworth RM, Jones IS. Capillary hemangioma of the lids and orbit: an analysis of the clinical features
and therapeutic results in 101 cases. 28 May 201526

27.  Reported ocular complications of orbital
haemangioma include amblyopia, optic neuropathy,
exposure keratopathy and strabismus.
 Thus, children with haemangiomas of the eyelid and
orbit often present ocular complications, with a
reported incidence in the range of 53% to 80%.*,**
*Haik BG, Jakobiec FA, Ellsworth RM, Jones IS. Capillary hemangioma of the lids and orbit: an analysis of the clinical features and therapeutic results in
101 cases. Ophthalmology 1979;86:760e92 (ISSN: 0161-6420).
**. Stigmar G, Crawford JS, Ward CM, et al. Ophthalmic sequelae of infantile hemangiomas of the eyelids and orbit. Am J Ophthalmol 1978;85:806.28 May 201527

28.  The high rates of amblyopia reported by Stigmar et
al (44%) * and Haik et al (50%) ** support the
relevance of early treatment in children with eyelid
or orbit haemangiomas in order to prevent
complications.
11. Stigmar G, Crawford JS, Ward CM, et al. Ophthalmic sequelae of infantile hemangiomas of the eyelids and orbit. Am J Ophthalmol
1978;85:806.
12. Haik BG, Karcioglu ZA, Gordon RA, et al. Capillary hemangioma (infantile periocular hemangioma). Surv Ophthalmol 1994;38:399e426.28 May 201528

29.  Direct intervention on the haemangioma using local
corticosteroids, laser treatment, embolisation or
surgery may be effective for superficial lesions, but
remains problematic and harmful for deep,
extensive forms such as intraorbital locations.
 Although systemic corticosteroids may be
efficacious and are most commonly prescribed, they
are often associated with major adverse reactions in
both the short- and long-term.
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30.  It was in a case of hypertrophic cardiomyopathy
treated with corticosteroids that Léauté-Labrèze
etal discovered the effectiveness of propranolol.
 Despite high doses of corticosteroids, that is,2-
5mg/kg per day of a prednisone equivalent, a
response (decrease or stabilisation of the
haemangioma) was obtained in only two-thirds of
cases.
. Le´aute´-Labre`ze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. New Engl J Med 2008;358:2650e
28 May 201530

31.  The effectiveness of propranolol no longer needs to
be demonstrated for eyelid and orbit forms,
subglottic locations or disseminated forms with
multi-organ damage.*,**,***
 The good overall tolerance of propranolol has also
been well established: propranolol is a non-cardio
selective beta-blocking agent that has been used for
many years in neonates for cardiovascular
indications such as hypertrophic myocardiopathies
or certain forms of tachycardia. *****
*. Fay A, Nguyen J, Jakobiec FA, et al. Propranolol for isolated orbital infantile hemangioma. Arch Ophthalmol 2010;128:256e8.
**. Taban M, Goldberg RA. Propranolol for orbital hemangioma. Ophthalmology 2010;117:195e195.e4.
*** Truong MT, Chang KW, Berk DR, et al. Propranolol for the treatment of a life-threatening subglottic and mediastinal infantile hemangioma. J
Pediatr 2010;156:335e8.
**** Fritz KI, Bhat AM. Effect of beta-blockade on symptomatic dexamethasone-induced hypertrophic obstructive cardiomyopathyin premature
infants: three case reports and literature review. J Perinatol 1998;18:38e44.
*****Kilian K. Hypertension in neonates causes and treatments. J Perinat Neonatal Nurs 2003;17:65e74.
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32.  At a dose of 0.5-4mg/kg per day, its tolerance in
neonates is excellent.
 The principle reported side effect, which is a rare
occurrence in infants treated for a haemangioma, is
hypoglycaemia in the Neonatal period or during
periods of fasting.
 Fainting with pallor , and episodes of cyanosis and
hypotension have also been described.
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33.  Treatment should be initiated in a paediatric facility
with monitoring of heart rate and blood pressure;
 drug administration can thereafter be continued
under ambulatory conditions in the form of capsules
prepared by a pharmacist according to body weight.
 Treatment should be continued until the end of the
haemangioma’s supposed growth period, that is, up
to 1year of age for the serious forms with a skin
component.
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34. THANKS
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35. NEXT
 Lecture
 Dr Abdul Aziz (Dry eye Disorder)
 Journal club
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