Management of Infantile Hemangioma
Ambika Hariharasubramony*, Sujatha Chankramath**
Department of Dermatology* and Paediatrics**, M V J Medical College and Research Hospital, Bangalore, Karnataka, India
Address for Correspondence
Dr. H Ambika, B601, Sriram Shrishti Apartments, Sumangali Sevashram Road, Anand Nagar, Hebbal, Bangalore 560032, India.
Email
ambs120269@yahoo.com
Keywords
hemangioma, vascular, therapy
Introduction

Infantile hemangiomas are the most common cutaneous tumors of childhood. (1) Infantile hemangiomas are vascular tumors which are present at birth as telangiectasic macule followed by rapid growth phase and a slow involution, leading to complete regression. (1) They have to be differentiated from congenital hemangiomas and malformations that are usually fully grown at birth and do not involute completely. (2) International society for study of vascular anomalies in 1996 classified vascular birth marks into vascular tumors and vascular malformations. (3) Infantile hemangiomas are more common in females than in males with ratio of 3:1. There is an increased incidence in premature and low birth weight infants and Caucasian ethnicity. (2) They are also more common after chorionic villous sampling. (4,5) Exact aetiology is not known. Since infantile hemangioma cells are positive for markers like GLUT-1, Lewis-Y, merosin, CCR6 similar to that of human placenta it is postulated that they are due to placental embolisation. There is decreased expression of vascular endothelial growth factor receptor (VEGFR 1) resulting in VEGF induced activation of VEGFR2 pathway leading to angiogenesis. Tissue hypoxia induces angiogenesis. (6)

Management of Small Uncomplicated Infantile Hemangioma

Management of infantile hemangioma varies according to site, size, complications, and stage of hemangioma and socioeconomic status of the patient and should be tailored to individual patient. Majority of them are smaller lesions and regress spontaneously. For smaller uncomplicated lesion of cosmetically less prominent area, active non-intervention is the policy adopted. Serial photographs are taken and consistent reassurance is given to parents and school going children regarding benign nature and spontaneous involution after a period of growth. Gentle massage, compression therapy with pressure dressing, application of ice can be done for proliferative phase. (7) Even smaller uncomplicated lesion if present in visibly prominent area can be emotionally disturbing to parents. They are often not ready to wait for years for regression and are worried about the subsequent scarring. Therapeutic option in such situation would be one which can cause involution without much side-effects. Topical and intralesional steroids are often used. Periorbital hemangioma is treated with 10mg/ml of triamcinolone acetonide at monthly intervals. (7) Two to 3 sittings are needed. (7). A study reported 85% of patients responded with 50% reduction in volume. (8) Complications include atrophy, depigmentation, eyelid necrosis, retinal artery embolism. (8). 5% imiquimod cream has been found useful. (9) The action is mediated through natural killer cells and interferon gamma which has antiangiogenic action. Side effects are minimal erythema and crusting can occur. (9) Topical 0.5% timolol eye drops, a non-selective beta blocker has shown excellent results. (10) It acts by vasoconstriction, decreases the growth factors and aids in apoptosis leading to involution. (10,11) No serious side effects reported except pruritus. (10) One study showed average regression in 3.3 months. (11) Systemic absorption is minimal after topical use of timolol. Prolonged use of timolol eye drops for glaucoma has reported side effects like Cheyne-Stokes breathing and exacerbations of asthma. (12,13) So caution is needed for large hemangioma and in children with cardiorespiratory abnormalities. Becaplermin (platelet derived growth factor) has been found useful in ulcerated infantile hemangioma of diaper area. Plermin increases mitogenesis of fibroblasts and helps in re-epithelization. (14) Local delivery of biphosphonates in treatment of hemangioma is under research. (15)

Management of Large Complicated Infantile Hemangioma

Larger hemangiomas develop complications especially during proliferative phase, most common being ulceration and bleeding. If they are near orifices, it can cause obstruction and impairment with vital functions like vision, feeding, excretion, respiration depending on the site of hemangioma. Such situations need immediate intervention. Besides these, hemangioma of tip of the nose, ear and lip are notorious for disfigurement. They also necessitate early intervention. (7) Systemic steroids can be used to cause faster reduction in size and are the drug of choice especially in life threatening situation. (7) Recommended starting dose is 2 mg per kg body weight as single morning dose and gradually tapered. Steroids have direct inhibitory effect on angiogenesis and they cause enhanced expression of genes coding for markers of apoptosis. They also act by increasing the sensitivity of vessels to vasoconstrictor substances by decreasing 17 beta oestrodiol. (16) High dose of steroids has its own side effect which has to be weighed against benefits. Caution is needed in children regarding growth retardation and in giving live vaccines. (17) Forty percent of hemangioma show rebound after stopping steroid. (1) Thirty percent of hemangioma do not respond to systemic steroids. (7) Recently promising results are reported with systemic propranolol, a non-selective beta blocker. (18) started as 2mg per kg bodyweight orally. Mechanism of action is similar to that mentioned with timolol. Results are excellent. Reduction in size of hemangioma is faster and involution occurs completely. (18) But extreme caution is needed in administering propranolol. Vigilant monitoring of blood glucose, cardiac and respiratory system is to be done during treatment. (19) Life threatening hemangiomas that fail to respond to systemic steroids can be treated with interferon alpha given subcutaneously.1-3 million units/m2. It acts by inhibiting angiogenesis. (20) Flu like syndrome, spastic diplegia, neutropenia, renal failure are some of the side effects. (19) Other immunosuppressive agents like cyclophosphamide, vincristine and intralesional bleomycin are also used for hemangiomas that are refractory to conventional treatments. (21-26) Cidofovir, an antiretroviral drug has antiangiogenic activity, further studies are needed about its use in life-threatening hemangioma. (2) Surgical treatment in hemangioma has narrowed its role to pedunculated hemangiomas and redundant scar following involution. (27) Moreover scar following surgery may be worse than that of spontaneous regression. Circular excision followed by purse string suture has shown minimum scar. (27) Cryotherapy can be used to hasten involution but its use is limited due to scarring. (28,29) Sclerotherapy with hypertonic saline and sodium citrate are no longer used. Sclerotherapy with polidocanol has shown convincing results. (30) Superficial hemangiomas can be treated effectively with Flash lamp pulsed dye laser. It is also useful in persistent telangiectasia after involution. Pulsed Nd YAG has greater penetration and can be used for deeper lesions but scarring is unavoidable. Carbon dioxide laser can be used in surgical intervention. (6)

Complications need special care. Large segmental facial hemangioma may be associated with PHACES syndrome and needs special care before starting treatment with beta blockers. One study has reported effective clearance with topical timolol. (9) Beard area hemangioma may be associated with subglotic hemangiomas and may require tracheotomy. (6) Multiple hemangiomas may be associated with hepatic hemangiomas and are treated with arterial embolisation. (6) Thalidomide inhibits angiogenesis and is found useful in case of life-threatening intracranial haemangiomas. (31)

Conclusion

Majority of hemangiomas are smaller lesions which undergo spontaneous resolution without much sequel. Cosmetically disfiguring and emotionally disturbing lesions even if small has to be treated with modalities which have minimum side effects. Complicated and life-threatening lesions needs immediate attention with agents that cause faster regression. Treatment option should be individualized and carefully chosen to give maximum benefit to the patients.
References :
  1. Miller T, Freidan IJ. Vascular tumours. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ (eds). Fitzpatrick's Dermatology in General Medicine. 7 Th ed. New York
  2. Frieden IJ. Infantile hemangioma research: looking backward and forward. J Invest Dermatol. 2011; 131: 2345-2348  [Google Scholar]  [Pubmed]  [CrossRef]
  3. Enjolras O, Mulliken JB. Vascular tumors and vascular malformations (new issues). Adv Dermatol. 1997; 13: 375-423  [Google Scholar]  [Pubmed]
  4. Amir J, Metzker A, Krikler R, Reisner SH. Strawberry hemangioma in preterm infants. Pediatr Dermatol. 1986; 3: 331-332.  [Google Scholar]  [Pubmed]  [CrossRef]
  5. Burton BK, Schulz CJ, Angle B, Burd LI. An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS). Prenat Diagn. 1995; 15: 209-214.  [Google Scholar]  [Pubmed]  [CrossRef]
  6. Boscolo E, Bischoff J. Vasculogenesis in infantile hemangioma. Angiogenesis. 2009;12: 197-207.  [Google Scholar]  [Pubmed]  [CrossRef]
  7. Mendiratta V, Jabeen M. Infantile hemangioma: an update. Indian J Dermatol Venereol Leprol. 2010; 76: 469-475.  [Google Scholar]  [Pubmed]  [CrossRef]
  8. Chen MT, Yeong EK, Horng SY. Intralesional corticosteroid therapy in proliferating head and neck hemangiomas: a review of 155 cases. J Pediatr Surg. 2000; 35: 420-423.  [Google Scholar]  [Pubmed]  [CrossRef]
  9. Martinez MI, Sanchez-Carpintero I, North PE, Mihm MC Jr. Infantile hemangioma: clinical resolution with 5% imiquimod cream. Arch Dermatol. 2002; 138: 881-884  [Google Scholar]  [Pubmed]  [CrossRef]
  10. Khunger N, Pahwa M. Dramatic response to topical timolol lotion of a large hemifacial infantile haemangioma associated with PHACE syndrome. Br J Dermatol. 2011; 164: 886-888  [Google Scholar]  [Pubmed]  [CrossRef]
  11. Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a pilot study. Arch Dermatol. 2010; 146: 564-565.  [Google Scholar]  [Pubmed]  [CrossRef]
  12. Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 2010; 128: 255-256.  [Google Scholar]  [Pubmed]
  13. Ni N, Langer P, Wagner R, Guo S. Topical timolol for periocular hemangioma: report of further study. Arch Ophthalmol. 2011; 129: 377-379.  [Google Scholar]  [Pubmed]  [CrossRef]
  14. Metz BJ, Rubenstein MC, Levy ML, Metry DW. Response of ulcerated perineal hemangiomas of infancy to becaplermin gel, a recombinant human platelet-derived growth factor. Arch Dermatol. 2004; 140: 867-870.  [Google Scholar]  [Pubmed]  [CrossRef]
  15. Yu H, Qin A. Could local delivery of biphosphonates be a new therapeutic choice for hemangiomas? Med Hypotheses. 2009; 73: 495-497  [Google Scholar]  [Pubmed]  [CrossRef]
  16. Hasan Q, Tan ST, Gush J, Peters SG, Davis PF. Steroid therapy of a proliferating hemangioma: histochemical and molecular changes. Pediatrics. 2000; 105: 117-120.  [Google Scholar]  [Pubmed]
  17. Hasan Q, Tan ST, Xu B, Davis PF. Effects of five commonly used glucocorticoids on haemangioma in vitro. Clin Exp Pharmacol Physiol. 2003; 30: 140-144.  [Google Scholar]  [Pubmed]
  18. Blei F, Chianese J. Corticosteroid toxicity in infants treated for endangering hemangiomas: Experience and guidelines for monitoring. Int Pediatr 1999; 14: 146-153.
  19. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008; 358: 2649-2651.  [Google Scholar]  [Pubmed]  [CrossRef]
  20. Ricketts RR, Hatley RM, Corden BJ, Sabio H, Howell CG. Interferon-alpha-2a for the treatment of complex hemangiomas of infancy and childhood. Ann Surg. 1994; 219: 605-612  [Google Scholar]  [Pubmed]  [CrossRef]
  21. Chang E, Boyd A, Nelson CC, Crowley D, Law T, Keough KM, et al. Successful treatment of infantile hemangiomas with interferon-alpha-2b. J Pediatr Hematol Oncol. 1997; 19: 237-244.  [Google Scholar]  [Pubmed]  [CrossRef]
  22. Fawcett SL, Grant I, Hall PN, Kelsall AW, Nicholson JC. Vincristine as a treatment for a large haemangioma threatening vital functions. Br J Plast Surg. 2004; 57: 168-171.  [Google Scholar]  [Pubmed]  [CrossRef]
  23. Moore J, Lee M, Garzon M, Soffer S, Kim E, Saouaf R, Effective therapy of a vascular tumor of infancy with vincristine. J Pediatr Surg. 2001; 36: 1273-1276.  [Google Scholar]  [Pubmed]  [CrossRef]
  24. Hurvitz SA, Hurvitz CH, Sloninsky L, Sanford MC. Successful treatment with cyclophosphamide of life-threatening diffuse hemangiomatosis involving the liver. J Pediatr Hematol Oncol. 2000; 22: 527-532.  [Google Scholar]  [Pubmed]  [CrossRef]
  25. Kullendorff CM. Efficacy of bleomycin treatment for symptomatic hemangiomas in children. Pediatr Surg Int. 1997; 12: 526-528.  [Google Scholar]  [Pubmed]  [CrossRef]
  26. Muir T, Kirsten M, Fourie P, Dippenaar N, Ionescu GO. Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int. 2004; 19: 766-773  [Google Scholar]  [Pubmed]  [CrossRef]
  27. Mulliken JB, Rogers GF, Marler JJ. Circular excision of hemangioma and purse-string closure: the smallest possible scar. Plast Reconstr Surg. 2002; 109: 1544-1554;  [Google Scholar]  [Pubmed]  [CrossRef]
  28. Cremer H. Cryosurgery for hemangiomas. Pediatr Dermatol. 1998; 15: 410-411  [Google Scholar]  [Pubmed]  [CrossRef]
  29. Reischle S, Schuller-Petrovic S. Treatment of capillary hemangiomas of early childhood with a new method of cryosurgery. J Am Acad Dermatol. 2000; 42: 809-813.  [Google Scholar]  [Pubmed]  [CrossRef]
  30. Winter H, Drager E, Sterry W. Sclerotherapy for treatment of hemangiomas. Dermatol Surg. 2000; 26: 105-108.  [Google Scholar]  [Pubmed]  [CrossRef]
  31. Frei-Jones M, McKinstry RC, Perry A, Leonard JR, Park TS, Rubin JB. Use of thalidomide to diminish growth velocity in a life-threatening congenital intracranial hemangioma. J Neurosurg Pediatr. 2008; 2: 125-129.  [Google Scholar]  [Pubmed]  [CrossRef]
Last Updated : Saturday, December 01, 2007 Vol 4 Issue 12 Art #
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