++
++
A baby girl is brought to the office because her mother is concerned over the growing strawberry hemangioma on her face. Her mother is reassured that most of these childhood hemangiomas regress over time and that there is no need for immediate treatment (Figure 115-1).
++
++
Hemangiomas are the most common benign tumors of infancy, affecting approximately 5% to 10% of children with Caucasian ethnicity.1
++
Up to 70% of hemangiomas are small and of cosmetic concern only and will resolve at the predictive rate of 10% per year, that is, 50% will have involuted by age 5; 90% by age 9.2
++
Segmental morphology, large size, and location on the face are predictive of poorer outcomes as measured by complication rates and suggest the need for further investigative study.3
++
Infantile hemangiomas, angiomas. Strawberry hemangiomas are also called superficial hemangiomas of infancy. Cavernous hemangiomas are also called deep hemangiomas of infancy.
++
Approximately 30% of hemangiomas are present at birth; the other 70% appear within the first few weeks of life.
Although the most predictive condition involving infantile hemangioma is low birth weight, other factors to be considered are prematurity, fair-skinned infants, female sex (2.4:1), and even in some cases family history.1,4
In one study, the mothers of children with hemangiomas are of higher maternal age, have a higher incidence of preeclampsia and placenta previa, and are more likely to have had multiple-gestation pregnancies.5
+++
ETIOLOGY AND PATHOPHYSIOLOGY
++
Hemangiomas consist of an abnormally dense group of dilated blood vessels.
Hemangiomas are characterized by an initial phase of rapid proliferation, followed by spontaneous and slow involution, often leading to complete regression.
Vascular malformations do not exhibit rapid proliferation but rather grow in proportion to the child and are considered a separate and distinct diagnosis with differing treatment regimens.
Most childhood hemangiomas are small and innocuous, but some grow to threaten a particular function or even life.
Rapid growth during the first month of life is the historical hallmark of hemangiomas, when rapidly dividing endothelial cells are responsible for the enlargement of these lesions. The hemangiomas become elevated and may take on numerous morphologies (dome-shaped, lobulated, plaque-like, and/or tumoral). The proliferation phase occurs during the first year, with most growth taking place during the first 6 months of life. Proliferation then slows and the hemangioma begins to involute.
The involutional phase may be rapid or prolonged. No specific feature has been identified in explaining the rate or completeness of involution. However, in one type of hemangioma, the rapidly involuting congenital hemangioma, the proliferation phase occurs entirely in utero such that the lesion is fully developed at birth, followed by complete involution during the second year of life.
Of the lesions that have involuted by age 6 years, 38% will leave residual evidence of the hemangioma in the form of a scar, telangiectasia, or redundant, "bag-like" skin. The chance of a permanent scar increases the longer it takes to involute. For example, of the lesions that involute after age 6 years, 80% may exhibit a cosmetic deformity requiring surgical intervention. Surgical intervention should only be performed by trained specialists because of the propensity for excessive bleeding from these vascular lesions.6
++
Early lesions may be subtle, resembling a scratch or bruise, or alternatively may look like a small patch of telangiectasias or an area of hypopigmentation. A hemangioma can start off as a flat red mark, but as proliferation ensues, it grows to become a spongy mass protruding from the skin. The earliest sign of a hemangioma is blanching of the involved skin with a few fine telangiectasias followed by a red macule. Rarely, a shallow ulceration may be the first sign of an incipient hemangioma. Hemangiomas are typically diagnosed based on appearance, rarely warranting further diagnostic tests.7
++
Hemangiomas may be superficial, deep, or a combination of both. Superficial hemangiomas are well defined, are bright red, and appear as nodules or plaques located above clinically normal skin (see Figure 115-1). Deep hemangiomas are raised flesh-colored nodules, which often have a bluish hue and feel firm and rubbery (Figure 115-2).
++
++
Most are clinically insignificant unless they impinge on vital structures, ulcerate, bleed, incite a consumptive coagulopathy, or cause high-output cardiac failure or structural abnormalities. Blocking vision is a common reason needed for treatment (Figures 115-3 and 115-4).
++
++
++
Anywhere on the body, most often on the face, scalp, back, or chest.
++
Most hemangiomas of infancy do not need imaging. If the hemangioma is very large, deep, or undefined, MRI with and without IV gadolinium helps delineate the location and extent of hemangiomas while also differentiating them from high-flow vascular lesions, such as arteriovenous malformations.7 Ultrasound is a useful tool to differentiate hemangiomas from other subcutaneous structures such as cysts and lymph nodes as well as from other soft-tissue masses but is limited in determining the depth or extent of the hemangioma.8
++
Plain radiography may be useful for evaluating hemangiomas that impinge on an airway.7
++
Biopsies are rarely needed and can be risky because vascular lesions may bleed profusely. If a biopsy is being considered, referral is recommended.
+++
DIFFERENTIAL DIAGNOSIS
++
Superficial capillary malformations that are frequently seen in infants include those above the eyelids and nape of the neck. These are called salmon patches and are not dangerous. The "angel's kisses" on the eyelids (Figure 115-5) usually disappear by age 2 years. The "stork bites" may last into adulthood but are rarely an issue because they are often covered by hair (Figure 115-6). These capillary malformations are a variant of nevus flammeus or port-wine stain. They are macular, sharply circumscribed, pink to purple, and varied in size (see Chapter 211, Hereditary and Congenital Vascular Skin Lesions).
Blue rubber bleb nevus syndrome—Bluish cutaneous vascular malformations that empty with pressure; texture resembles rubbery nodules, similar to deep hemangiomas.9
Maffucci syndrome—Rare congenital nonhereditary mesodermal dysplasia characterized by multiple enchondromata, cutaneous hemangiomas, and more recently spindle cell hemangiomas.10 It is important to identify Maffucci syndrome early because it is associated with an increased risk of malignancy. May appear as multiple vascular malformations of the skin with a "grape-like" appearance (see Chapter 211, Hereditary and Congenital Vascular Skin Lesions).
Angiosarcoma—Rare, malignant endothelial tumor characterized as ill-defined red patches, plaques, or nodules (see Chapter 210, Acquired Vascular Skin Lesions).11
Arteriovenous malformation—Benign, single red papules on head or neck; may be cutaneous or mucosal.11
Infantile fibrosarcoma—A rare and highly malignant tumor of childhood that may take on the form of a highly vascularized mass, resembling a hemangioma, especially after a hemangioma has ulcerated as a result of rapid proliferation.12
++
++
++
The majority of hemangiomas will eventually involute without complications and require no treatment, but approximately 20% cause complications such as ulcerations or irreversible cutaneous expansion, or threaten vital structures such as the eyes, nose, or airways.13
Hemangiomas in trauma-prone areas are the most likely to ulcerate. These include the diaper area (Figure 115-7) and the back of the head. Small ulcerations can be treated with topical mupirocin in morning and metronidazole gel in the evening. SORⒸ
Any lower face or beard area hemangioma can be a marker for laryngeal hemangiomatosis (Figure 115-8). Snoring or frequent cough in such a child should prompt a referral to a head and neck surgeon.
Any large segmental hemangioma on the face could be part of the PHACE syndrome:
P—Posterior fossa malformations
H—Hemangiomas, usually large, segmental, "plaque-like" lesions (Figure 115-9)
A—Arterial anomalies
C—Cardiac anomalies and coarctation of the aorta
E—Eye abnormalities, that is, microphthalmos, exophthalmos, colobomas, retinal vascular abnormalities, optic nerve atrophy, or iris hypertrophy or hypoplasia. A coloboma is a hole in one of the structures of the eye that can cause blindness (Figure 115-10).
++
++
++
++
++
Beta blockers are now the first-line therapy for cosmetically significant or function-impairing and rapidly proliferating infantile hemangiomas. Propranolol (FDA approved, 20 mg/5 mL) 1 mg/kg to 3 mg/kg dosages were used in the largest randomized controlled trial to date for treatment durations of 3 to 13 months, with the median length of treatment being 6 months (see Figure 115-10). The benefit of continuing treatment beyond 12 months is not clear.14,15 SORⒷ
++
Propranolol treatment can cause side effects such as diarrhea, sleep disturbance, electrolyte abnormalities, and/or cold extremities. Watch for the major side effects (which would warrant cessation of therapy), hypotension and hypoglycemia. Bronchial hyper-reactivity has also been reported. Monitoring the patient in the office after the first dose is advisable, although the treatment has been found to be safe in a number of studies.14,15
Combined treatment with propranolol and 940-nm diode laser for particularly severe hemangiomas was shown to be more effective for cosmesis in one study.16 Other studies have had differing results, with combined laser/propranolol treatment showing little to no advantage from the added laser therapy over propranolol alone.17
For patients who cannot tolerate beta blocker therapy, prednisone 3 to 5 mg/kg per day had been shown to provide an effective and rapid way of treating hemangiomas, and in fact, was the treatment of choice prior to the discovery of beta blocker treatment for this condition.18 SORⒷ In a study, 68% of patients receiving systemic corticosteroid treatment with oral prednisone experienced rapid and virtually complete involution of hemangiomas.18 Another 25% experienced significant regression, and treatment demonstrated no effect in 7% of patients. The authors recommended treating with oral prednisone for 6 to 8 weeks, and in more severe cases, for 12 weeks.
Side effects of oral steroid therapy include Cushingoid facies, mood changes/irritability, hypertension and increased susceptibility to infection, and short-term growth retardation, all of which seem to be transient and resolve after cessation of the therapy.18
Ultrapotent topical corticosteroids have been found especially helpful in the treatment of small hemangiomas, especially periocular hemangiomas and those at sites prone to ulceration and disfigurement. Seventy-four percent of patients demonstrated good or at least partial response to treatment, with the majority experiencing cessation of growth before what would have been expected for their age. Thinner, more superficial hemangiomas demonstrated better improvement than thicker, deeper lesions.19 SORⒷ
Intralesional corticosteroid injections, composed of a mixture containing triamcinolone acetonide (20 mg average dose) and betamethasone acetate (3 mg average dose) with varying number of injections, have been found to successfully treat head and neck childhood hemangiomas in properly selected infants. In a research study, 13% of the hemangiomas treated with intralesional injections almost completely involuted, 32% showed greater than 50% reduction in volume, 32% showed definite but less than 50% reduction in volume, and 23% showed little to no decrease in size.20 SORⒷ Avoid intralesional steroids around the eye.
Treatment with flashlamp-pumped pulsed-dye laser has been found to be an effective treatment method for superficial cutaneous hemangiomas at sites of potential functional impairment and on the face. In a study, 85% of patients were found to have excellent or good results with the flashlamp-pumped pulsed-dye laser. Hemangiomas with a deep component do not seem to benefit from flashlamp-pumped pulsed-dye laser therapy to the same degree as a truly superficial hemangioma, as the laser is limited by its depth of vascular injury.21-23 SORⒷ The pulsed-dye laser seems especially promising with its ability to selectively damage blood vessels with minimal damage to surrounding tissues. This procedure is also associated with decreased pain and increased healing.24 SORⒷ
Facial hemangiomas causing severe functional disturbance and serious psychological distress are strong reasons to consider surgical excision before the child reaches the expected age of spontaneous regression. SORⒸ
Large periocular hemangiomas demand prompt treatment to prevent debilitating consequences such as amblyopia (see Figure 115-2). Early treatment is also recommended for proliferative labial tumors because they not only have a tendency to bleed, but they also make eating difficult. Additionally, early treatment with a consideration for surgery is advised for hemangiomas located on the nasal tip, as they regress slowly and may ultimately result in distortion of the nasal framework.23
Surgical excision of involuted hemangiomas is not uncommon to remove residual tissue that may be causing cosmetic or functional impairment. Excision is performed in late involution to reduce the risk of hemorrhage.
Depending on the location and how complex the hemangioma is, consultations with pediatric dermatologists, ophthalmologists, otolaryngologists, plastic surgeons, and pediatric neurosurgeons may be necessary to ensure proper care.
++
Topical timolol ophthalmic gel or solution has been shown in a number of studies to effectively treat infantile hemangiomas (Figure 115-8).25-27 SORⒷ One of the studies noted that predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04).16 SORⒷ Another study using 0.5% ophthalmic solution 3–4 times daily in patients with small superficial hemangiomas found that treatment was most effective in the early proliferative stage.25 SORⒷ
++
Watchful waiting and serial observations during well-child examinations are recommended for uncomplicated hemangiomas of infancy. Hemangiomas with complicating factors need close follow-up on an individual basis.
++
Hemangiomas are benign and are not cancer. They are common, and up to 10% of lighter skinned infants will have one. Most hemangiomas will go away spontaneously and not need treatment. For those needing treatment, there are treatments that are safe and effective (oral propranolol and topical timolol). Feel free to show the great results of therapy of some of the largest and most worrisome hemangiomas in this chapter to the parents in your office (Figures 115-9, 115-10, 115-11).
++
++
++
+
Acknowledgment
++
We thank Mary Alice for the photographs of her daughter with PHACE syndrome. One can learn more about their family story at http://angelphace.com/. Also visit www.PHACEsyndromecommunity.org, the site for the organization that supports individuals with PHACE and their families.
1. +
Munden
A, Butschek
R, Tom
WL,
et al. Prospective study of infantile hemangiomas: incidence, clinical characteristics and association with placental abnormalities.
Br J Dermatol. 2014:170:907.
[PubMed: 24641194]
3. +
Haggstrom
AN, Drolet
BA, Baselga
E,
et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treatment.
Pediatrics. 2006;118:882.
[PubMed: 16950977]
5. +
Haggstrom
AN, Drolet
BA, Baselga
E,
et al. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics.
J Pediatr. 2007;150(3):291–294.
[PubMed: 17307549]
6. +
Achauer
BM, Chang
CJ, Vander Kam
VM. Management of hemangioma of infancy: review of 245 patients.
Plast Reconstr Surg. 1997;99(5):1301–1308.
[PubMed: 9105356]
8. +
Dubois
J, Patriquin
HB, Garel
L,
et al. Soft-tissue hemangioma in infants and children: diagnosis using Doppler sonography.
AJR Am J Roentgenol. 1998;171(1):247–252.
[PubMed: 9648798]
9. +
Elewski
BE, Hughey
LC, Parsons
ME. Differential Diagnosis in Dermatology. St. Louis, MO: Elsevier; 2005:545.
10. +
McDermott
AL, Dutt
SN, Shavda
SV, Morgan
DW. Maffucci's syndrome: clinical and radiological features of a rare condition.
J Laryngol Otol. 2001;115(10):845–847.
[PubMed: 11668006]
11. +
Barnhill
RL. Vascular tumors. In: Hunt
SJ, Santa Cruz
DJ, Barnhill
RL, eds. Textbook of Dermatopathology. New York: McGraw-Hill; 1998:821.
12. +
Yan
AC, Chamlin
SL, Liang
MG,
et al. Fibrosarcoma: a masquerader of ulcerated hemangioma.
Pediatr Dermatol. 2006;23(4):330–334.
[PubMed: 16918626]
13. +
Anjolras
O, Wassef
M, Mazoyer
E,
et al. Infants with Kasabach-Merritt syndrome do not have "true" hemangiomas.
J Pediatr. 1997;130(4):631–640.
[PubMed: 9108863]
14. +
Leaute-Labreze
C, Hoeger
P, Mazereeuw-Hautier
J,
et al. A randomized, controlled trial of oral
propranolol in infantile hemangioma.
N Engl J Med. 2015;372(8):735–746.
[PubMed: 25693013]
15. +
Drolet
BA, Frommelt
PC, Chamlin
SL,
et al. Initiation and use of
propranolol for infantile hemangioma: report of a consensus conference.
Pediatrics. 2013;131(1):128–140.
[PubMed: 23266923]
16. +
Deme
T, Jones
S. The treatment of problematic hemangiomas in children with
propranolol and 940nm diode laser.
J Pediatr Surg. 2016;51(5) 863–868.
[PubMed: 26970851]
17. +
Bin
Y, Li
L, Li-xin
Z,
et al. Clinical characteristics and treatment options of infantile vascular anomalies. Medicine. 2015;94:40.
18. +
Sadan
N, Wolach
B. Treatment of hemangiomas of infants with high doses of
prednisone.
J Pediatr. 1996;128(1):141–146.
[PubMed: 8551406]
19. +
Garzon
MC, Lucky
AW, Hawrot
A, Frieden
IJ. Ultrapotent topical corticosteroid treatment of hemangiomas of infancy.
J Am Acad Dermatol. 2005;52:281–286.
[PubMed: 15692474]
20. +
Sloan
G, Reinisch
J, Nichter
L,
et al. Intralesional corticosteroid therapy for infantile hemangiomas.
Plast Reconstr Surg. 1989;83:459–466.
[PubMed: 2919200]
21. +
Rizzo
C, Brightman
L, Chapas
AM,
et al. Outcomes of childhood hemangiomas treated with the pulsed-dye laser with dynamic cooling: a retrospective chart analysis.
Dermatol Surg. 2009;35:1947.
[PubMed: 19889007]
23. +
Demiri
EC, Pelissier
P, Genin-Etcheberry
T,
et al. Treatment of facial haemangiomas: the present status of surgery.
Br J Plast Surg. 2001;54(8):665–674.
[PubMed: 11728108]
24. +
Eedy
DJ, Breathnach
SM, Walker
NPJ. Surgical Dermatology. Oxford, UK: Blackwell Science; 1996:245.
25. +
Oranje
AP, Janmohamed
SR, Madern
GC, de Laat
PC. Treatment of small superficial haemangioma with
timolol 0.5% ophthalmic solution: a series of 20 cases.
Dermatology. 2011;223:330–334.
[PubMed: 22179543]
26. +
Chakkittakandiyil
A, Phillips
R, Frieden
IJ,
et al.
Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study.
Pediatr Dermatol. 2012;29:28–31.
[PubMed: 22150436]
27. +
Semkova
K, Kazandjieva
J. Topical
timolol maleate for treatment of infantile haemangiomas: preliminary results of a prospective study.
Clin Exp Dermatol. 2013;38(2):143–146.
[PubMed: 22731954]