I. Landells, MD, FRCPC
Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
Although hemangiomas are frequently encountered in pediatric practice, their management has been controversial because they are notoriously unpredictable, especially in early infancy. In the past, clinicians believed that infant and childhood hemangiomas were best left untreated, due to spontaneous involution and the adverse effects of treatments such as radiotherapy and surgery.1 However, today there is an increased awareness of both the physical and psychological sequelae associated with hemangiomas, a small percentage of which can be life threatening and this has resulted in a renewed push to treat them. Furthermore, therapeutic advances have been made, and new therapies are on the horizon.
active non-intervention, hemangiomas, PHACES Syndrome
Hemangiomas, benign tumors of infancy, occur in 1-2% of newborns and up to 10% of children aged ≥ 1 year.2 Fifty five percent present at birth, while the rest develop within the first few weeks of life. They are more commonly found in premature infants weighing less than 1500gm,2 and a female’s chance of being affected is three times greater than a male’s.3
Typically, hemangiomas begin as pale blue-red macules with superficial telangiectases. Over the next 8-14 months they proliferate rapidly into bright red elevated plaques if they are superficial. If they lie deeper within the skin they appear as a bluish nodule. They are most commonly a combination of both.3,4 The proliferative phase is followed by slow involution, and almost all hemangiomas resolve spontaneously over time. By 5 years of age, 50% of hemangiomas involute, 70% by age 7, and 90% by age 9.2,3 Approximately 20-40% leave residual changes in the skin, which can have a lasting psychological effect. Approximately 10% require treatment, and less than 1% are life threatening. Hemangiomas are usually solitary, but up to 20% of affected children have multiple lesions.3
Past and Current Therapies
Historically, the treatment of hemangiomas usually involved surgical excision or radiation. Today, while it is recognized that most hemangiomas do not need treatment, ‘active nonintervention’, rather than ‘benign neglect’ is advised.1 Before and after photographs are extremely helpful in reassuring parents of the natural involution of this phenomenon.3
Hemangiomas that threaten life or an important bodily function, such as vision or the airway, do require intervention. Recognizing high risk hemangiomas and being aware of all possible associated malformations, e.g., PHACES syndrome (Posterior fossa malformations, Hemangiomas of the cervicofacial region, Arterial anomalies, Cardiac anomalies, Eye anomalies and Sternal or abdominal clefting or ectopia cordis), is essential to ensure the patient receives the most appropriate treatment and to reduce sequelae. For example, midline hemangiomas can be markers for occult spinal malformations, and anomalies of the anorectal and urogenital regions. Consequently, spinal imaging should be done.3
For management, a multidisciplinary approach is best, including dermatology, pediatrics, plastics and radiology.2 In the more severe cases, psychological and social support services can also be helpful. Essentially, the type and location of hemangioma, the associated complications, as well as the patient’s age should guide the treatment.
Hemangiomas That Require Treatment
Lesions that require treatment include:
- life and function threatening hemangiomas, e.g., those causing impairment of vision, Kasabach-Merritt coagulopathy, respiratory compromise, congestive heart failure, hepatic involvemen
- hemangiomas in certain anatomic locations that often leave permanent scars or deformity, especially the nose, lip, ear, and glabellar area
- large facial hemangiomas, especially those with a prominent dermal component (more likely to leave permanent scarring)
- smaller visible hemangiomas, (e.g., the face and hands) may be considered for treatment with modalities unlikely to cause scarring or significant side effects
- ulcerated hemangiomas
- pedunculated hemangiomas (likely to leave significant fibrofatty tissue after involution)
- hemangiomas that are psychologically disturbing, such as lesions on the face, hands and feet.2
While the mechanism of action for corticosteroids is unknown, there are data to suggest that vasoconstriction of arterioles and precapillaries may be responsible, and it has been suggested that steroid therapy works by increasing the sensitivity of arterioles and precapillaries to other, physiologically occurring vasoconstrictive agents.5 Certain steroids inhibit angiogenesis in the presence of a fragment of heparin. Triamcinolone reduced the transcription of the growth factors, PDGF-A and -B, IL-6, TGF- β1 and – β3. Furthermore, there was up-regulation of the mitochondrial cytochrome b gene expression.6
Superficial hemangiomas requiring treatment, with the exception of those affecting vision or causing respiratory distress, are generally treated with either localized use of corticosteroids (potent topical or intralesional) or with pulsed dye laser.1
The use of triamcinolone, 20mg/ml, can be used as intralesional corticosteroid therapy for any small, bossed, facial hemangioma. The drug should be injected at low pressure, using a 3ml syringe and 25-gauge needle.7 The dose should not exceed 3-5mg/kg per procedure. Treatment in the periocular region is contraindicated except by an experienced ophthalmologist, as there is a risk of embolic occlusion of the retinal artery or oculomotor nerve palsy.3
During the injection of any facial lesion, the surrounding tissue should be compressed, either digitally or with the finger ring of an instrument. Usually three to five injections are needed, given at 6-8 week intervals. The response rate is similar to that for systemic corticosteroids. If there is necrotic tissue and/or secondary infection, the injections should not be undertaken.7
Resulting complications have been few, although serious consequences may result. Shorr and Seiff8 reported a case of central retinal artery occlusion due to retrograde blood flow. This resulted from the force of injection or digital pressure, which in turn propelled steroid suspension particles into the central retinal artery. Full thickness eyelid necrosis may be related to spontaneous thrombosis within the lesion. Linear subcutaneous fat atrophy following lymphatic channels has been reported, but remits spontaneously.9
As a mainstay of treatment for serious cases, the most common choice is oral prednisone, at a dosage of 2-4mg/kg/day given either in a single morning dose or divided doses in emergent cases. Within days approximately 1/3 of affected infants exhibit dramatic shrinkage of the hemangioma. Stabilization of growth without measurable shrinkage can be seen in another third, and minimal or no effect in the final third. Increasing the dosage does not enhance results in situations where there is poor response. If effective, corticosteroids must be continued for the entire anticipated proliferative phase or regrowth will occur.1,3,4
Infants treated with systemic corticosteroids need to be observed for adverse effects such as growth retardation, blood pressure elevation, insulin resistance, and immunosuppression. Moon facies have been recorded as a side effect of prednisone. However, they disappear shortly after treatment is completed.5
at periorbital and periocular regions
Otitis; decrease in auditory conduction
when involving the ear, may obstruct the external auditory canal
may delay speech development
may be associated with diffuse or multiple cutaneous hemangiomas, and large facial hemangiomas
Airway obstruction or associated airway involvement
cutaneous hemangiomas that involve the chin, lips, mandibular region, “beard distribution” area and neck at greatest risk for this complication
Hoarseness and stridor
may progress rapidly to respiratory failure
Kasabach-Merrit phenomenon (KMS)
kaposiform hemangioendotheliomas or tufted angiomas
does not have typical hemangiomas. KMS can lead to significant morbidity and bleeding, but this is not a complication of true hemangiomas, as was previously believed.
Table 1: Possible complications caused by hemangiomas.3
Although interferon alpha has shown very promising results, there have been reports of neurotoxicity,4 and it should be reserved for use only in life threatening cases where high-dose corticosteroid treatment has failed.3 It has a limited role in treating subglottic hemangiomas.
Both interferon alpha-2a and alpha-2b are usually administered as a subcutaneous (SC) injection of 3 million U/m2 of body-surface area per day.3 Regular neurological monitoring before and during treatment is mandatory.4 For high-risk hemangiomas SC interferon alpha-2a should be given, at an initial dose of 1 million U/m2/day, which is then increased to 3 million U/m2/day if tolerated.2
Common side effects, including irritability, neutropenia, liver enzyme abnormalities, and spastic diplegia, were recently reported in 20% of patients.3
Pulsed Dyed Laser
Flash-lamp-pumped pulsed dye laser works well for small, superficial lesions and for some large, plaque-like lesions. However, there is only a brief window of opportunity during infancy when hemangiomas are thin enough to be effectively treated with this laser, because its penetration is limited to approximately 1.2mm. It can improve residual telangiectases after involution. Though it has not been proven reliable in eliminating ulcerated hemangiomas, this treatment can result in reduced pain and prompt reepithelialization.1
Rarely, laser treatments can induce ulceration, and shallow scars may develop, even at relatively low fluences. For unknown reasons, this type of scarring seems to occur more commonly in infants with hemangiomas than in infants with port wine stains.1
Intralesional Laser Therapy
In one study the ND:YAG laser was reported to be useful for treating large capillary/cavernous hemangiomas, often rendering an inoperable lesion safely resectable, or markedly decreasing the size and functional impact of the lesion.10
The benefits and risks of surgery must be weighed carefully, since the scar may be worse than the results of spontaneous regression.3 Generally, it is recommended that a re-evaluation be done when the child is 4 years old, in order to assess the potential benefit of excision. Factors such as the extent of residual hemangiomas must be considered if:
- the involution is slow
- there is post ulcerative scarring, unalterably expanded skin, or a high probability of fibrofatty residuum
- surgery is likely to have a good result.1
Surgery is especially good for small, pedunculated hemangiomas and occasionally, in cases where there may be functional impairment. It is usually used to repair residual cosmetic deformities.3 Nasal and labial hemangiomas seem to involute more slowly. In the case of nasal tip hemangioma, the tumor can be debulked using unilateral/bilateral rim incisions, which allow the skin to contract by whatever elasticity remains.7 General anesthesia is usually required for children younger than 10 years of age, but older patients can sometimes be managed with local anesthesia.7
Other treatment modalities
In exceptional cases, when earlier therapies have failed cyclophosphamide, embolization, radiotherapy, and sclerotherapy may be considered. A recent study evaluated the use of sclerotherapy for treating hemangiomas over a period of 20 years (1975-1995). A total of 157 patients found it to be a relatively simple, inexpensive, and effective form of therapy. In the study, sclerotherapy with polidocanol was carried out on monstrous or rapidly growing cavernous hemangiomas that were mainly localized on the face. The results showed that one to three injections were sufficient to maintain the sclerosis effect and long-term aesthetic results were encouraging. No severe complications were observed.11 Evolving therapies include leuprolide acetate, a GnRH agonist with antiproliferative effects, ketotifen (Zaditor®, Zaditen®, Ciba Visions/Novartis), new selective lasers, and new angiogenesis inhibitors. 2
Major goals of treatment
When treating a hemangioma, the major goals should include:
- prevention or reversal of any life-threatening or functionthreatening complications
- prevention of permanent disfigurement left by residual skin changes after involution
- minimization of psychosocial distress from the presence of hemangiomas for the patient and his/her family
- avoidance of aggressive, potentially scarring procedures for treatment of those hemangiomas likely to have an excellent prognosis without therapy
- prevention or adequate treatment of ulcerated hemangiomas to minimize scarring, infection, and pain.2
Most hemangiomas require no treatment. However, active nonintervention is recommended in order to recognize those that may require treatment quickly. When treatment is undertaken, it is important that it be customized to the individual patient, and that the possible physical, and psychological complications be discussed in advance. Often, a multidisciplinary approach is recommended. In cases where treatment must be undertaken, it is important that it not be delayed. Rapid tapering or discontinuation of treatment in the proliferative phase should be avoided.
- Frieden IJ. Which hemangiomas to treat – and how? Arch Dermatol 133:1593-5 (1997 Dec).
- Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines of care for hemangiomas in infancy. AAD Guidelines/Outcomes Committee. J Am Acad Dermatol 37(4):631-7 (1997 Oct).
- Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med 341(3):173-81 (1999 Jul).
- Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med 341(3):173-81 (1999 Jul).
- Sadan N, Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. J Pediatr 128(1):141-6 (1996 Jan).
- Hasan Q, Tan ST, Gush J, Peters SG, Davis PF. Steroid therapy of a proliferating hemangioma: histochemical and molecular changes. Pediatrics 105(1 Pt 1):117-20 (2000 Jan).
- Roberts LJ. Management of hemangiomas. Pediatr Dermatol 14(1):57-83 (1997).
- Shorr N, Seiff SR. Central retinal artery occlusion associated with periocular corticosteroid injection for juvenile hemangioma. Ophthalmic Surg 17(4):229-31 (1986 Apr).
- Reyes BA, Vazquez-Botet M, Capo H. Intralesional steroids in cutaneous hemangioma. J Dermatol Surg Oncol 15(8):828-32 (1989 Aug).
- Burstein FD, Simms C, Cohen SR, Williams JK, Paschal M. Intralesional laser therapy of extensive hemangiomas in 100 consecutive pediatric patients. Ann Plast Surg 44(2):188-94 (2000 Feb).
- Winter H, Drager E, Wolfram S. Sclerotherapy for treatment of hemangiomas. Dermatol Surg 26(2):105-8 (2000 Feb).