2. F Thoumazet, CLeaute-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 rst 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 Disguring lesion, many do not need to be treated.
About 20% of haemangiomas are extremely disguring 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 28 May
20154
5. Treatment options Corticosteroids are considered to be
rst-line therapy for problematic infantile capillary haemangiomas*
Other therapeutic options include vincristine and interferon-a** In
2008, Laut Labrze 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. ***Leaute-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 28 May 20155
6. METHODS An experimental clinical trial was launched in
November 2007 that included children with severe disguring
infantile capillary haemangiomas involving the periocular region.
28 May 20156
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 28 May
20157
8. Diagnosis was made by : Clinical examination, Colour Doppler
ultrasound and MRI in cases where intraorbital extension was
suspected. 28 May 20158
9. The children were followed at each examination visit by: 28
May 20159 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. 28 May 201510
11. At each visit were performed Fundoscopy, Retinoscopy
Photography Visual acuity 28 May 201511
12. The side-effects of beta-blockers were carefully monitored
: acrocyanosis, pulmonary functions drowsiness, blood pressure
monitoring, irritability, echocardiography gastric acid backward
ow. rhythm cardiac monitoring 28 May 201512
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 28 May
201513
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: attening 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 rst 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. 28 May 201519
20. Regression on MRI : in certain infants, with minimal
residual lesion of the intraorbital haemangioma after 3months of
treatment. 28 May 201520
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 28 May 201522
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. 28 May 201523
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 rst 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, ONeil JW, DElia VJ, et al.
SubTenons 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 supercial strawberry haemangioma in 25
patients, and a strawberry haemangioma without deep lid orbital
swelling in one patient. Proptosis and ocular displacement were
common ndings 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 supercial lesions, but remains problematic and
harmful for deep, extensive forms such as intraorbital locations.
Although systemic corticosteroids may be efcacious and are most
commonly prescribed, they are often associated with major adverse
reactions in both the short- and long-term. 28 May 201529
30. It was in a case of hypertrophic cardiomyopathy treated
with corticosteroids that Laut-Labrze 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. .
Leaute-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. 28 May 201531
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. 28 May 201532
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 haemangiomas
supposed growth period, that is, up to 1year of age for the serious
forms with a skin component. 28 May 201533
34. THANKS 28 May 201534
35. NEXT Lecture Dr Abdul Aziz (Dry eye Disorder) Journal club
28 May 201535