Abstract NEW ENGLAND JOURNAL OF MEDICINE Hemangiomas in Children Beth A. Drolet, MD; Nancy B. Esterly, MD; Ilona J. Frieden, MD Hemangiomas are the most common soft-tissue tumors of infancy, occurring in approximately 5 to 10 percent of one-year-old children. Despite the frequency of these tumors, their pathogenesis is not completely understood, and the best approach to their management remains controversial. Research on angiogenesis, an improved knowledge of the classification of the vascular anomalies of infancy, advances in imaging techniques, recently identified complications, and new therapeutic approaches, such as treatment with interferon and lasers, have altered our understanding of this common childhood problem and the way we approach it. N Engl J Med. 1999;341:173-181.Reprints: Beth A. Drolet, MD, Pediatric Dermatology, Medical College of Wisconsin, Froedert East, 9200 W Wisconsin Ave, Milwaukee, WI 53226 (e-mail: firstname.lastname@example.org). Commentary HEMANGIOMAS ARE one of the most common tumors of infancy.1,2 Approximately 55% are present at birth, with the remainder appearing shortly thereafter. After a period of rapid growth and a plateau phase, they start to involute between the ages of 6 months and 2 years. When they occur in the adnexa or orbit, they are associated with a high incidence of anisometropia, amblyopia, and/or strabismus.1,3,4 Consequently, the ophthalmologist must be knowledgeable about the treatment of periorbital hemangiomas. Because of this, the excellent review of hemangiomas in infants by Drolet and coworkers2 that appeared recently in the New England Journal of Medicine was chosen for commentary in the ARCHIVES. These authors point out that, despite the prevalence of hemangiomas in infants, there is still controversy about their treatment. There is no single treatment that is ideal for all cases, and the treatment decision needs to take the size and location of the tumor into account. Based on the classification by Mulliken and Glowacki,5 many lesions that had previously been referred to as hemangiomas are in fact structural vascular malformations. Mulliken and Glowacki5 suggested limiting the use of the term hemangioma to vascular tumors that have a growth phase marked by hypercellularity, and endothelial proliferation followed by an involutional phase. The etiology of hemangiomas is unclear; however, it is known that there is an increased incidence in premature infants, and a substantial increase (approximately 10-fold) in infants born to women who had undergone chorionic-villous sampling during pregnancy. Hemangiomas occur 3 times as frequently in girls than in boys; at times they can be familial. Drolet and coworkers2 point out that all infants with a hemangioma in the periorbital region need to be evaluated by an ophthalmologist, citing the high incidence of deleterious effects of these lesions on the visual system. I would carry their admonition one step further by suggesting that the ophthalmologic examination of an infant who has a periorbital hemangioma must include cycloplegic retinoscopy and determination of whether amblyopia is present. If means are not available to assess visual acuity in a preverbal child, and if strabismus is not present to allow for assessment of fixation preference, the induced-tropia test to check for amblyopia should be included as part of the evaluation. Often the decision to treat or not treat a periorbital hemangioma in an infant is based on anisometropia that is increasing in amount or the development of amblyopia. Merely observing that the tumor does not occlude the visual axis is insufficient justification for conservative treatment, as the most common cause of vision loss in infants with periorbital hemangiomas is anisometropic amblyopia.3,4 Drolet and coworkers2 point out some important associations that ophthalmologists should be aware of. The presence of multiple cutaneous hemangiomas has a high association with visceral hemangiomas, which can often be hard to diagnose and frequently require abdominal ultrasound. When there is visceral involvement, Drolet and coworkers report that the morbidity and mortality can range from 40% to 80%. Thus ophthalmologists must be aware of this association when seeing a child with periorbital plus multiple other cutaneous hemangiomas, and should seek appropriate consultation. The authors also point out that hemangiomas have a predilection for occurring in the subglottic region, and involvement in that area can rapidly cause respiratory failure. Sixty percent of infants with multiple hemangiomas of the head and neck (particularly in the beard distribution) get respiratory involvement from a subglottic hemangioma. The ophthalmologist caring for an infant with hemangiomas in this area should look for signs of hoarseness and stridor. The authors also point out that extensive hemangiomas of the head and neck can be associated with multiple anomalies. The PHACES syndrome (posterior fossa malformations, hemangiomas of the cervicofacial region, arterial anomalies, cardiac anomalies, eye anomalies, and sternal or abdominal clefting or ectopia cordis) affects girls 9 times as frequently as boys. Infants with this syndrome are at risk for cerebrovascular occlusive disease. Drolet and coworkers2 point out that, despite the availability of newer treatment options in recent years, there is still controversy about the treatment of infantile hemangiomas. They suggest that there should not be a uniform approach and that the treatment should be individually tailored to the size and location of the lesion. During the 1940s and 1950s, hemangiomas were treated primarily with radiation or excision. A high frequency of complications from those treatments led to an era of "benign neglect" in treating hemangiomas in infants, based on the premise that they ultimately will involute. In addition to the previously stated effect that an untreated periorbital hemangioma can have on the visual system, there is increasing evidence that lesions of this type anywhere on the face can have serious adverse psychosocial consequences. Drolet and coworkers consider systemic steroids to be the mainstay in treating infantile hemangiomas, with a recommended dose of 2 to 3 mg/kg per day of prednisone or prednisolone. The use of interferon alfa-2a or interferon alfa-2b has been shown to be effective in treating hemangiomas; however, Drolet and coworkers point out that up to 20% of treated infants develop spastic diplegia that is potentially irreversible, and recommend reserving that treatment for life-threatening tumors that fail to respond to systemic steroids. In some cases, depending on the size and nature of the lesion, local excision may be a wise choice. Pulsed-dye lasers may be effective in treating port-wine stains or very thin superficial hemangiomas; however, because their depth of penetration is limited to approximately 1 mm, they are less effective for larger lesions. They can be useful in treating residual telangiectasia that can persist after involution of a hemangioma, or for treating ulceration of a hemangioma. During the past 20 years, intralesional injection of periorbital hemangiomas has been a popular treatment option.1,3,4 It tends to have the benefit of delivering the most medication where it is most needed, and thus results in fewer systemic complications than oral prednisone. I have the impression that intralesional steroids are the treatment of choice for a large number of pediatric ophthalmologists and oculoplastic surgeons. Therefore, it is of concern that in their otherwise thoughtful article, Drolet and coauthors summarily dismiss intralesional steroid injection of periocular hemangiomas as " . . . contraindicated, since it is fraught with complications."2(p179) I find the statement "fraught with complications" to be misleading, as it implies a high frequency of complications. In fact, no serious complications were found in an aggregate of more than 200 cases of infantile periocular hemangiomas treated with intralesional steroids.3 Drolet and coworkers based their statement on 2 isolated cases of serious vision-related complications with periocular intralesional steroid injection. These cases involved retinal vascular occlusion after injection of a periocular hemangiomas. I believe the choice of treatment of a periocular hemangioma needs to come from a balanced assessment of relative risks and benefits. I am unaware of reports of any other treatments that have been as successful as intralesional steroids in decreasing the incidence of amblyopia that can result from infantile hemangiomas. Although rare vision-related complications have been reported from this treatment, there is convincing evidence that these complications may relate to dosage, volume of injection, choice of steroid (particle size), or injection technique (pressure of injection). For example, the case cited by Drolet and coworkers of "blindness" after injection, received more than 6 times the maximum dosage that Drolet et al recommends. It was the equivalent of giving a 67.5-kg person approximately 2625 mg of prednisone.3,6 Subsequently, in a reply to a letter to the editor, Drolet and coworkers agreed that their initial recommendation regarding intralesional injection of corticiosteroids for periocular hemangiomas should be modified in light of the information summarized earlier.7 They agreed the risk of the rare complication of vision loss must be weighed against the possibility of vision loss from the hemangioma, as well as the risks of other treatment choices. Unfortunately, individuals reading the original article in the New England Journal of Medicine may not be aware of this modified recommendation. As physicians, our role should be to give parents all the information necessary to make informed decisions, especially in situations which there is no clear-cut best treatment option. It is the parents of the infants who must assume the risk. In my own experience, most parents choose intralesional injection when presented with the available data regarding efficacy and complications. Accepted for publication January 11, 2000. Corresponding author: Burton J. Kushner, MD, Department of Ophthalmology, University of Wisconsin Hospital and Clinics, 2870 University Ave, Suite 206, Madison WI 53705 (e-mail: email@example.com). References 1. Haik BKarcioglu ZGordon RAPechous BP Capillary hemangioma (infantile periocular hemangioma). Surv Ophthalmol. 1994;38399- 426Google ScholarCrossref 2. Drolet BAEsterly NBFrieden IJ Hemangiomas in children. N Engl J Med. 1999;341173- 179Google ScholarCrossref 3. Kushner BJ Hemangiomas in children [letter]. N Engl J Med. 1999;3412018Google ScholarCrossref 4. Kushner BJ Infantile orbital hemangiomas. Int Pediatr. 1990;5249- 257Google Scholar 5. Mulliken JBGlowacki J Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg. 1982;69412- 420Google ScholarCrossref 6. Kushner BJ Bilateral retinal embolization associated with intralesional corticosteroid injection for capillary hemangioma of infancy [letter]. J Pediatr Ophthalmol Strabismus. 1993;30397- 398Google Scholar 7. Drolet BAEsterly NBFrieden IJ Hemangiomas in children [letter]. N Engl J Med. 1999;3412018- 2019Google ScholarCrossref
Archives of Ophthalmology – American Medical Association
Published: Jun 1, 2000
Keywords: hemangioma,neoplasms,infant,vascular anomalies,human leukocyte interferon,interferons,lasers,soft tissue neoplasms,diagnostic imaging
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