8 Treatment of Infantile Hemangiomas



10.1055/b-0034-101164

8 Treatment of Infantile Hemangiomas

Milton Waner, Teresa Min-Jung O, and Aaron Fay

8.1 Introduction


Given the natural history of an infantile hemangioma (hereafter, “hemangioma”, a cycle of proliferation and involution), one should always weigh the benefit of conservative management against active intervention. The discovery of propranolol as a medical treatment for hemangiomas radically changed our approach to these lesions 1 ,​ 2 ; this drug has become a first-line therapy in the management of hemangiomas. Nonetheless, the age-old question concerning whether or not to treat must first be considered. Traditional thinking dictated a conservative approach predicated on the belief that all hemangiomas will involute. Although it is true that all hemangiomas do involute, the definition of involution and its clinical significance must be explored. Involution is a process that affects all hemangiomas; however, the end point is not always acceptable ( Fig. 8.1 ). Any residual hemangioma of the head and neck is likely to permanently affect the psychosocial well-being of the patient. 3 ,​ 4

Fig. 8.1 An involuted infantile hemangioma (result is unacceptable).

Histologically, proliferating vascular endothelial cells undergo apoptosis and are replaced by hypovascular fibrofatty tissue. Concomitant clinical changes include a diminution in the size of the mass. The mass will “disappear” in about 50% of cases, and in the remainder, a fibrofatty mass will remain. 5 If the overlying skin was involved, then reduced vascularity brought about by involution will translate into a reduction in erythema. At times, all the erythema will disappear, but in about 50% of cases, erythema will persist, often in the form of telangiectasias.


Unfortunately, during proliferation, the papillary dermis is often replaced with hemangioma. This layer contains the adnexal structures (sweat glands, sebaceous glands, and hair follicles) that are essential to normal healing. In addition, the dermal layer is rich in collagen and elastin. During involution, the papillary dermis does not regenerate. 5 The skin becomes atrophic owing to an absence of normal dermal collagen ( Fig. 8.2 ). Therefore, in about half of the cases, an atrophic scar overlying a fibrofatty mass will persist, even though this lesion has “involuted.” Involution, therefore, does not necessarily mean the lesion will disappear; it means only that it will shrink.

Fig. 8.2 (a) Child with a paranasal hemangioma. (b) The hemangioma after involution. The residuum consists of fibrofatty tissue with overlying atrophic scarring.

What was once considered acceptable may not meet today’s standards as an acceptable end point. Furthermore, there is no way to predict a hemangioma’s behavior. It is generally accepted that early involuters (i.e., by age 6 years) are likely to yield the best results, whereas late involuters are likely to require intervention. 6



8.2 Indications for Treatment


Because hemangiomas vary greatly in their presentation, guidelines concerning the need for intervention are essential. As a rule, one should consider treating a lesion only when doing so will offer a distinct advantage to conservative management. Several factors must be considered: first, an infant’s healing environment differs greatly from that of an older child. Infants and very young children produce less transforming growth factor β1 (TGF-β1)-induced collagen and less scar tissue. In contrast, older children produce copious amounts of TGF-β1-induced collagen and hence more scar tissue. The ratio of TGF-β1 and TGF-β2 to TGF-β3 is lower. The collagen quality is fine and reticular with less crosslinking and is laid down more rapidly. An incised wound in an infant is therefore more likely to heal with little to no scar tissue than the same wound in an older child. This factor should also influence the timing of any planned surgery or laser treatment. Second, mesenchymal stem cells are more readily mobilized during the healing process of an infant than in an older child, translating to, once again, less scarring, and underscores the value of treating at a younger age. 7 ,​ 8 ,​ 9 Third, anatomical location and size play important roles in the decision to treat. A 2-cm hemangioma on the tip of a child’s nose will pose a different problem compared with the same size lesion at the base of the occiput or on the child’s back.



8.2.1 Lesions to Consider for Treatment




  • Any facial or clearly exposed hemangioma



  • Any lesion that is unlikely to involute completely and in whom intervention will result in a more favorable outcome



  • Any complication warrants treatment. Complications include ulceration, functional impairment, cardiac failure, and disfigurement.



  • Airway lesions



  • Periocular lesions warrant special attention due to their propensity to cause amblyobia.


Once a decision to intervene has been made, the choice of modality will then be made. Three factors are important in this determination:




  • The lesion subtype: focal or segmental (see Chapter 4’s Fig. 4.1)



  • The stage of the disease: proliferating or involuting



  • The depth of the lesion: superficial, deep, or compound


The chosen treatment is best undertaken by a multidisciplinary team, which should include the following specialties: pediatric otolaryngology–head and neck surgery, pediatric dermatology, hematology, oncology, interventional radiology, plastic surgery, and ophthalmic plastic surgery.



8.3 Medical Treatment



8.3.1 Propranolol


Since it was first introduced in 2008, 1 propranolol has become an extremely popular drug, rapidly surpassing all other modalities. In fact, in most centers that frequently treat hemangiomas, propranolol has become the first-line therapy. 10 ,​ 11 Propranolol is a nonselective β1, β2 antagonist. Its exact mechanism of action is still unknown. The medication is taken 2 to 3 times a day and is well tolerated. Side effects of particular concern include bronchospasm and hypoglycemia. 12 ,​ 13 ,​ 14 ,​ 15 Currently, healthy patients do not need hospital admission for initiation of therapy. Patients require a pretreatment electrocardiogram while a full cardiac evaluation is nonessential. On the other hand, children with preexisting medical conditions, cardiac anomalies, or prematurity should be monitored during an inhospital admission.


Topical β-blockers have also been reported to be effective in treating very superficial hemangiomas and are an alternative treatment. 16 Several case reports have been published, all reporting encouraging results; however, concerns regarding the bioavailability of the drug in neonates and infants are valid. Timolol gel-forming solution (Timolol GFS), the more popular form, appears to be up to 10 times more potent than propranolol. 17 ,​ 18 Although precise correlates are unknown, each drop of topical timolol may represent between 2 and 8 mg of oral propranolol. When applied near a mucous membrane or to an ulcerated surface, significant amounts may be systemically absorbed. 19


Studies are now exploring the use and efficacy of selective B1 antagonists, although some physicians still advocate the use of oral corticosteroids. 20 The role of oral corticosteroids has been significantly displaced by the advent of propranolol. Steroids are now rarely prescribed and are only used when propranolol is contraindicated, or for adjuvant use in airway disease.


Refer to Chapter 7 for further information regarding propranolol as a medical treatment for infantile hemangioma (IH).



8.3.2 Vincristine


Systemic vincristine is a microtubule-disrupting agent that inhibits angiogenesis. 21 This drug became popular in cases of steroid failure or as an adjuvant to steroids where their long-term use was becoming problematic. Vincristine was also useful in treating kaposiform hemangioendotheliomas. 22 ,​ 23 Nowadays, vincristine is rarely used. Propranolol contraindication or failure warrants the consideration of systemic vincristine use.



8.4 Laser Treatment


Laser treatment became popular in the early 1990s and remains useful for the treatment of superficial hemangiomas or the superficial component of a deep lesion. 24 ,​ 25 ,​ 26 The laser most widely used is a pulsed dye laser. Unfortunately, light at this wavelength (585 nm) is rapidly attenuated in human skin and has an effective therapeutic depth of only 1 to 2 mm. 24 ,​ 27 Neodymium: yttrium aluminum garnet (Nd:Yag) lasers are in the near-infrared spectrum and are more effective for the deeper component because of their ability to penetrate deeper, 28 but the higher risk of scarring with these lasers has precluded them from widespread use.



8.4.1 Superficial Hemangiomas


Although not all early superficial lesions warrant treatment, there are advantages to early treatment, especially where there has been replacement of the dermis with hemangioma. Early treatment can reduce or eradicate a superficial dermal hemangioma ( Fig. 8.3 ). If treated early enough, it will allow the return of normal dermis and prevent atrophic scarring so commonly seen after involution. Laser treatment is effective, and with repeated treatment every 4 to 6 weeks, excellent results can be expected.

Fig. 8.3 (a,b) Pulsed dye laser treatments of segmental facial hemangioma.

Oral propranolol is also effective in these cases, but it may not be warranted (a small lesion) or the parents of the child may object to a systemic therapy. Topical β-blockers have also been reported to be effective in treating very superficial hemangiomas and are an alternative. 16 Again, the bioavailability of the drug is unknown in neonates and infants, and care must therefore be taken near the mucous membranes or ulcerated lesions. Laser treatment remains a viable alternative when treating superficial proliferating hemangiomas.


Repeated laser treatments can be effective in treating superficial hemangiomas. 29 During the proliferative phase, treatments every 4 weeks are recommended. Parameters vary from center to center but the end point of a successful treatment is a purpuric color change to the lesion, which will dissipate over the course of 10 to 12 days. Treatment with a pulsed dye laser is painful, and so for smaller lesions, treatment can be administered as an office procedure with topical anesthesia. For larger lesions and in older children, general anesthesia will be necessary.



8.4.2 Superficial Component of a Compound Hemangioma


Lasers can be effectively used to treat the superficial component of a compound lesion, especially if the deep component has been or will be surgically removed. Once again, a purpuric end point is indicative of a successful treatment. Several treatments spaced at six-week intervals are usually necessary to achieve an acceptable end point.


Occasionally, after several treatments, a telangiectatic pattern of larger vessels persists. These vessels can be seen as discrete vessels, and because of their larger size, they require a greater thermal load to obliterate them, which can be done with either a diode laser or an Nd:YAG laser (in conjunction with dynamic skin cooling). Intense pulsed light–emitting devices can also be used.



8.4.3 Quiescent or Involuting Hemangiomas


Once systemic treatment has commenced or is completed, superficial vascular ectasias frequently remain. The precise incidence of this has not been published, but it is frequent enough to warrant discussion. The most effective treatment is with a pulsed dye laser. Occasionally some of the telangiectasias that persist are larger vessels in the range of 200 µm or greater ( Fig. 8.4 ). In these cases, far more thermal energy is needed to destroy these vessels, and a diode laser with a smaller spot size (1 mm) or a Nd:YAG laser with cooling may be effective.

Fig. 8.4 Cutaneous telangiectasias remaining after treatment with propranolol only. These lesions respond well to a diode laser.


8.5 Surgical Treatment



8.5.1 Indications for Surgery


The indications for surgery are not uniform and vary from center to center. In general, indications for surgery include the following.



Failed Conservative Therapy

This category includes lesions that have, for whatever reason, been allowed to proliferate and then involute without any form of treatment. At some point, it becomes obvious that the lesion is unlikely to involute adequately. Alternatively, the child has reached a level of maturity where it is obvious that he or she is aware of the lesion and is psychologically affected by it.



Failed Medical Therapy

In our experience, propranolol is more efficacious with segmental hemangiomas than with focal lesions. In many instances, propranolol will fail to shrink a hemangioma completely. Surgery is therefore indicated.



Surgery Is Likely to Provide the Best Outcome

In some instances, especially when dealing with focal hemangiomas, treatment with propranolol will, at best, result in a mere shrinkage of the hemangioma. In these instances, surgery may provide a better outcome ( Fig. 8.5 ).

Fig. 8.5 (a) Focal lip infantile hemangioma before treatment with propranolol. (b) Three months on propranolol. Nonresponder.

For the purpose of simplicity, surgical management is discussed by anatomical sites:




  • Lip



  • Orbital/periorbital



  • Nasal



  • Cheek



  • Forehead and scalp



  • Parotid



  • Airway



8.5.2 Hemangiomas of the Lip


Infantile hemangiomas of the lip often impede function (speech and feeding) and lead to disfigurement. Additionally, there is a high incidence of ulceration. When ulceration occurs, treatment should be administered as soon as possible, as this condition can be very painful, bleed, and become a site of infection.


As with all anatomical sites, lip hemangiomas can be classified into focal and segmental patterns of tissue involvement. There are distinct sites of occurrence of focal as well as segmental IHs. Segmental IHs may involve the maxillary, frontonasal, or mandibular segments. The lower lip is the most common site of both focal and segmental lip IHs. 30


Because of these sites of predilection, the anatomical extent and distortion can be predicted. With this in mind, we have developed surgical guidelines for their management. 30 Regarding the upper and lower lips, apart from skin staining, the lip may be elongated in its vertical or its horizontal dimension ( Fig. 8.6 ), and inversion or eversion of the lip with oral incompetence may be present. These dimensions can be corrected, and the surgical approach will depend on the site of the hemangioma.

Fig. 8.6 (a,b) Lip infantile hemangioma causes elongation of the lip in the horizontal and/or vertical dimensions.

Oftentimes, the lip has been expanded (especially in focal lesions), and thus more than 30% of the lip can be excised without causing microstomia. Incisions are placed along boundaries of facial subunits (alar groove, philtrum, vermiliocutaneous junction [VCJ], wet-dry mucosal margin): access to the lesion is easy, and any redundant tissue can then be removed with an acceptable cosmetic result.


Lower-lip focal hemangiomas are the most common focal lesions and tend to involve the lateral aspect of the lower lip ( Fig. 8.7 ). These lesions frequently lengthen and evert the lower lip. The lip can be lengthened by as much as 50%, depending on the size of the hemangioma. These lesions can almost always be resected via a wedge excision.

Fig. 8.7 (a,b) Focal hemangioma treated with primary surgical excision. Residual skin staining is treated with a pulsed dye laser, which will afford a better outcome compared with medical therapy or laser treatment.

Propranolol has made the most impact on the treatment of segmental hemangiomas. With early treatment, most of the deformities can be prevented. Too often, however, this is not done, and devastating functional as well as aesthetic abnormalities will result.


Frontonasal segmental lesions are the most difficult because they distort the philtrum ( Fig. 8.8 ). The vertical height of the upper lip is usually lengthened. These lesions can be approached via the VCJ or the inferior border of the columella and the nasal sill.

Fig. 8.8 (a,b,c) Frontonasal lip infantile hemangioma. Note distortion of the philtrum. Surgical approach: incisions placed along boundaries of facial subunits. (Used with permission from O TM, MD, Scheuermann-Poley, Tan M, Waner M. Distribution, clinical characteristics, and surgical treatment of lip infantile hemangiomas. JAMA Facial Plast Surg. 2013;15(4):292-304.)

Maxillary or V2 segmental lesions elongate the hemilip and invert the VCJ. They are usually approached along the VCJ, extending up the philtrum and across the nasal sill and ala.


The most common segmental hemangioma involves the entire lower lip (mandibular segment). Because ulceration is frequent, the VCJ is usually distorted and the concavity between the VCJ and the labiomental crease is obliterated. These lesions also lengthen the lower lip. A wedge resection of the lower lip will correct the horizontal lengthening. An incision along the VCJ will correct the inversion as well as the convexity below the VCJ. A specially modified suture technique will help to re-create the natural sulcus of the lower lip.


Each of the preceding procedures may require a staged approach to prevent overresection and may also require postoperative pulsed dye laser therapy for superficial erythema or CO2 Fraxel treatment or dermabrasion of atrophic scarring from involuted hemangioma.

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Jun 15, 2020 | Posted by in HEAD AND NECK SURGERY | Comments Off on 8 Treatment of Infantile Hemangiomas
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