1. 1. 28 May 20151
2. 2. F Thoumazet, CLeaute-Labre`ze, J Colin, B Mortemousque Br J Ophthalmol 2012
3. 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. 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. 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. 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. 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. 8. Diagnosis was made by : Clinical examination, Colour Doppler ultrasound and MRI in cases where intraorbital extension was suspected. 28 May 20158
9. 9. The children were followed at each examination visit by: 28 May 20159 general pediatrician, pediatric dermatologist, ophthalmologist radiologist
10. 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. 11. At each visit were performed Fundoscopy, Retinoscopy Photography Visual acuity 28 May 201511
12. 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. 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. 14. 28 May 201514
15. 15. We observed a 100% response to treatment, as follows: Clinical regression Ultrasonographic regression Regression on MRI 28 May 201515
16. 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. 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. 18. Flattening infantile haemangioma after 24 h of systemic propranolol.28 May 201518
19. 19. Ultrasonographic regression: with a decrease in lesion thickness , increase in resistance index of blood vessels on Doppler imaging. 28 May 201519
20. 20. Regression on MRI : in certain infants, with minimal residual lesion of the intraorbital haemangioma after 3months of treatment. 28 May 201520
21. 21. Intra-orbital haemangioma on MRI: total regression following 3.5 months of systemic propranolol. 28 May 201521
22. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 34. THANKS 28 May 201534
35. 35. NEXT Lecture Dr Abdul Aziz (Dry eye Disorder) Journal club 28 May 201535