REVIEW ARTICLES

Vascular Skin Lesions in Children: A Review of Laser Surgical and Medical Treatments
LAUREN M. CRAIG, BA,
AND

TINA S. ALSTER, MD*

Vascular anomalies are a common nding in children. Although most of these lesions are benign, they can be a severe cosmetic problem and cause structural and functional damage to nearby tissues. As a result, physicians are tasked with developing effective treatment options with superior safety proles. Vascular anomalies may be divided into tumors and malformations. Vascular tumors, such as infantile hemangiomas, typically appear a few months after birth, whereas the majority of vascular malformations, such as port-wine stains, are present at birth. Although these lesions vary in appearance, etiology, and disease course, many are treated in a similar fashion. In this review, we focus on treatment modalities for some of the more-prevalent childhood vascular lesions, including port-wine stains, primary telangiectasias, infantile hemangiomas, pyogenic granulomas, and angiomas. The authors have indicated no signicant interest with commercial supporters.

ascular anomalies are a common nding in children. Although most of these lesions are benign, they can be of severe cosmetic concern and can cause structural and functional damage to nearby tissues. As a result, physicians are tasked with developing effective treatment options with superior safety proles. Vascular anomalies may be divided into tumors and malformations. Vascular tumors, such as infantile hemangiomas, typically appear a few weeks after birth, whereas the majority of vascular malformations, such as port-wine stains, are present at birth. Although these lesions vary in appearance, etiology, and disease course, many are treated in a similar fashion. In this review, we focus on treatment modalities for some of the more-prevalent childhood vascular lesions, including port-wine stains (PWS), primary telangiectasias, infantile hemangiomas, pyogenic granulomas (PGs), and angiomas.

Vascular Malformations Port-Wine Stains Characteristics PWS, also known as nevus ammeus, are the most common childhood vascular malformation,

occurring in 0.3% of newborns.1 A PWS is a slowowing capillary malformation, described as a cluster of pink to purple, sharply demarcated patches. They are typically located in a unilateral distribution on the head and neck and may involve the mucous membranes. Like most vascular malformations, PWS are present at birth and do not involute spontaneously. Over time, these lesions darken, with 11% thickening and 24% developing nodules.2 PWS can be isolated malformations, or they may be associated with conditions that have systemic involvement. When PWS are located in a trigeminal distribution, Sturge-Weber syndrome, characterized by glaucoma, leptomeningeal venous angiomas, seizures, hemiparesis contralateral to the facial lesion, and intracranial calcications, must be considered. PWS may also be associated with other syndromes such as Proteus (with an overgrowth of the skeleton; skin, adipose, and central nervous system tissue; severe disgurement; tumors; pulmonary complications; deep vein thrombosis; and pulmonary embolism), BeckwithWiedemann (with exomphalos, macroglossia, and gigantism), and BonnetDechumeBlanc (with unilateral arteriovenous malformations involving the retinas, brain, and skin of the face).36 For this reason, children

*Both authors are afliated with Washington Institute of Dermatologic Laser Surgery, Washington, District of Columbia
2013 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc.  ISSN: 1076-0512  Dermatol Surg 2013;39:11371146  DOI: 10.1111/dsu.12129
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born with PWS should receive a complete diagnostic evaluation. Treatment Treatment is usually recommended for PWS even when they are not associated with an underlying systemic condition. These lesions can cause signicant morbidity, bleeding, and psychological and cosmetic concerns. The most effective treatment is vascular-specic laser therapy, most notably pulsed dye laser (PDL).7 Despite signicant technologic advances, many PWS cannot be completely eliminated with PDL treatment alone. As a result, physicians have become interested in combining existing therapies to maximize results. Laser PDLs emit wavelengths that specically target oxyhemoglobin, treating the vascular abnormality with minimal damage to the surrounding tissue. Effective treatment protocols include wavelengths of 585 to 600 nm, uences of 6 to 12 J/cm2, and pulse durations of 0.45 to 10 ms with concomitant epidermal cooling. Sequential treatment sessions every 4 to 8 weeks are recommended.8 Common side effects include transient erythema, edema, and mild purpura that spontaneously resolve in a few days. Progressive lesional fading is seen after each treatment, with multiple (  9) treatments typically necessary to achieve >75% improvement (Figure 1A,B).9 Studies have suggested that laser treatment is most effective when initiated in the rst year of life, in part because infant skin is thinner, thus enhancing laser penetration.10,11 As mentioned above, PWS become thick and nodular with advancing age, so treating early allows the malformation to be treated at its smallest. In addition to determining optimal laser parameters and appropriate patient treatment age, varying laser techniques have been investigated. A double-pass technique using a PDL produces better blanching

(A)

(B)

Figure 1. Port-wine stain before (A) and after (B) 12 laser treatments (six pulsed-dye laser (PDL) followed by six combination PDL and neodymium-doped yttrium aluminum garnet laser). Topical imiquimod may be helpful in further lesional lightening.

than the typical single pass technique.12 Treated areas are generally lighter, without evidence of scarring after a series of laser treatments, but residual PWS can darken over time because of progressive vessel ectasia.13 Longer wavelengths and pulse durations (along with more epidermal cooling to prevent excess tissue damage) can be applied to lesions that initially respond to PDL treatment but reach a treatment plateau.14 The long-pulse alexandrite (755 nm),15 long-pulse 1,064-nm neodymiumdoped yttrium aluminum garnet (Nd:YAG),16 and dual 595-nm PDL and 1,064-nm Nd:YAG17 lasers have proven useful in these latter cases, particularly when lesions have developed nodularity, because of the ability of these systems to achieve deeper dermal penetration.18

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Laser and Topical Therapy Although lasers continue to be used as the primary treatment for PWS, preliminary studies have evaluated the use of adjunctive anti-angiogenic therapy. Daily or three times weekly application of topical imiquimod 5% between laser treatment sessions has been shown to reduce PWS color reduction more than PDL treatment alone.19 Side effects of imiquimod treatment include minor skin irritation in a minority of patients.20 Other investigators have demonstrated in rodents that PDL treatment followed by a 14 day course of rapamycin prevented reformation and reperfusion of blood vessels more than PDL alone.21 Other Intense pulsed light (IPL) has also been advocated for PWS treatment. Although vascular-specic lasers remain a more-effective treatment option, IPL should be considered in PDL-resistant patients.22 A randomized side-by-side study showed that PDL was generally more effective in inducing clearance, but in PDL-resistant lesions, six of 15 patients had more than 75% clearance with IPL.23 Primary Telangiectasias Characteristics Telangiectasias appear as dilated blood vessels on the skin and mucus membranes. Primary (or essential) telangiectasias have no causative or coexisting cutaneous or systemic diseases. Although primary telangiectasias are usually a sporadic nding, a benign hereditary form has also been described. This condition, known as generalized essential telangiectasia, consists of patchy reticular telangiectasias that may progress to involve large body surface areas. Generalized essential telangiectasia can present at any age and has no known etiology, although familial cases have been described with an autosomal-dominant inheritance pattern.3 Children with telangiectasias should be fully evaluated to exclude causes of secondary telangiectasias such as connective tissue diseases, xeroderma pigmentosum, poikiloderma, and ataxia-telangiectasia.3

Treatment 3 As with PWS, PDL is the most commonly applied treatment for primary telangiectasias. Complete resolution of linear and spider facial telangiectasias is typically achieved after two to three sequential 595-nm PDL treatments using a 7- to 10-mm spot and uences from 6 to 10 J/cm2.7,24 Post-treatment purpura can be avoided using longer pulse durations (>6 ms), but lack of purpura after treatment generally yields less-favorable clinical results.25 Pulse stacking and use of multiple sequential passes have also been cited as techniques that may yield better clinical responses.26,27 Lasers with longer wavelengths, such as the long-pulse alexandrite (755 nm) and long-pulse Nd:YAG (1,064 nm) systems may be used for deeper lesions but may increase the risk of scarring and ulceration.

Vascular Tumors Infantile Hemangiomas Characteristics Hemangiomas are the most common tumor in infancy (12% incidence of all live births and  10% at 1 year of age), with a greater incidence in premature infants. These vascular tumors characteristically increase in size, stabilize, and then spontaneously involute over several months.28 Frieden and colleagues29 recently discovered that the most rapid hemangioma growth occurs before 8 weeks of age, especially between 5.5 and 7.5 weeks. In addition to prematurity, other risk factors include Caucasian race, female sex, chorionic villous sampling, and multiple-gestation pregnancy.1 Hemangiomas are typically classied as supercial, deep, or mixed.7 Supercial hemangiomas are the most common (5060% of cases), appearing bright red and sometimes protuberant. In contrast, deep hemangiomas are rare (15% of cases), less well dened, rm, cystic, or compressible and may exhibit a bluish hue underneath normal-appearing skin. Mixed hemangiomas combine characteristics of supercial and deep lesions and account for 25% to 30% of cases.28 Hemangiomas can also be

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classied as focal or segmental. Focal hemangiomas tend to grow in a tumor-like fashion, whereas segmental hemangiomas are larger and plaque-like. Segmental hemangiomas are more aggressive, with greater ulceration and local destruction.30 Left untreated, 60% of infantile hemangiomas will involute by 5 years, and 90% to 95% will maximally involute by 9 years. It was established in 2000 that glucose transporter-1 stains positive in hemangiomas, making this marker useful in distinguishing hemangiomas from other vascular tumors.31 Location does not appear to affect resolution in most situations, although lip lesions are the most persistent. Size does not appear to affect involution.1 Treatment 3 The majority of hemangiomas are treated with simple observation, because 70% resolve spontaneously without severe complications. The other 30% of hemangiomas may result in hemorrhage, ulceration, and disgurement of the underlying tissue.1 Depending on location, a hemangioma may cause airway or orbital obstruction, hearing loss, or spinal abnormalities. Early treatment is advised for hemangiomas that interfere with the function of a vital organ, involve large portions of the face or inguinal area, risk ulceration, or cause psychological suffering.32 Hemangiomas requiring treatment are most effectively managed early to affect the proliferation phase directly.33 A variety of treatments are available, including topical, intralesional, oral, and laser therapies. Oral 2 Oral corticosteroids have been the rst-line treatment for hemangiomas since the 1960s. A course of prednisone is generally effective in decreasing the size and severity of hemangiomas but can cause numerous side effects, including impaired immunity, hypertension, and hyperglycemia.3436 An effective dosing regimen consists of 1.5 to 2 mg/kg per day of prednisone for 4 to 8 weeks.32 One meta-analysis showed that 3 mg/kg might be a more effective dose, stabilizing growth in 90% of patients.34 Although

corticosteroids may still be prescribed, other therapies are currently advocated because of the risk of side effects associated with corticosteroid use. Recent studies favor the use of propranolol, a nonselective beta-adrenergic blocker, as rst-line treatment for infantile hemangiomas. Leaute-Labreze and colleagues37 rst discussed its use at a dose of 2 mg/kg per day. Other beta-blockers, such as acebutolol, have also been found to be effective, but propranolol use is generally favored.38 Price and colleagues39 found that propranolol therapy was more cost effective and had fewer surgical complications than oral steroids. Koay and colleagues40 reported that propranolol and oral steroids could be combined at lower doses, reducing the adverse side effects of both drugs. Young infants are commonly started on a course of propranolol while hospitalized to monitor for any adverse reactions, most commonly hypotension. Older children often start treatment as outpatients, with appropriate counseling and monitoring. Hypoglycemia has been cited as a rare and dangerous side effect of propranolol.41 Diarrhea and hyperkalemia have also been described.42,43 The appropriate course of propranolol has not been standardized, but physicians should be aware that hemangiomas can have rebound growth if treatment is not continued through the growth phasegenerally 1 year. Recombinant interferon-alpha (3 million U/m2 per day) and vincristine, a vinca alkaloid chemotherapy agent (0.05 mg/kg per day), have been used successfully to treat proliferative hemangiomas.1 These treatments are reserved as third-line therapy because of the risk of immunosuppressive side effects with vincristine and irreversible spastic diplegia with interferon-alpha.44

Intralesional and Topical Agents 2 Ophthalmologists rst used intralesional and topical steroids to treat periorbital hemangiomas.45 Because of concerns regarding ocular damage, intralesional therapies are more commonly applied on the lip and

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nose. Triamcinolone acetonide (10 mg/mL) injections are administered every 4 weeks at doses not exceeding 3 to 5 mg/kg per treatment.28 Class 1 topical corticosteroids are applied twice daily with monitoring every 2 weeks.46,47 Topical beta-blockers, specically timolol maleate 0.5% gel, have also been shown to be effective in treating supercial hemangiomas.48 Lastly, the use of 5% imiquimod, an immune modulator and upregulator of interferon-alpha, has been used as successful therapy alone or in combination with laser.49 Laser Vascular-specic PDL therapy is particularly useful in treating ulcerated hemangiomas, supercial hemangiomas, and postinvolution hemangiomas (Figure 2A,B). Laser treatment parameters are less aggressive (47 J/cm2, 0.451.5-ms pulse duration) than those used for other vascular abnormalities to reduce such side effects as ulceration, scarring, and hypopigmentation in these delicate lesions.5052 Multiple treatments are needed at 4- to 6-week intervals during the proliferative phase.53 PDL is less effective in the treatment of mixed and deep hemangiomas than in ulcerated, supercial or postinvolution lesions because it has limited dermal penetration. A recent study by Admani and colleagues54 found that early PDL treatment is a safe and effective option for selected patients with infantile hemangiomas alone or in combination with systemic therapy. In addition, involuted hemangiomas that display a variable array of cosmetic defects can be treated later with PDL, fractional laser skin resurfacing.55 or plastic surgery. Brightman and colleagues56 reported ve cases in which patients experienced 50% to 75% improvement in residual hemangioma textural skin irregularities with minimal side effects after ablative fractional laser skin resurfacing. Other Hemangiomas can be surgically excised, but the risk of postoperative scarring is high. Scarring is of particular concern when treating young children with lesions located in cosmetically sensitive areas

(A)

(B)

Figure 2. Infantile hemangioma before (A) and after (B) ve pulsed-dye laser (PDL) treatments. Concomitant use of oral propanol would have been anticipated to result in earlier lesional resolution.

such as the face and neck. Embolization is another treatment option for high-output lesions when there is the potential for cardiac failure.1 Pyogenic Granulomas Characteristics PGs, also referred to as lobular capillary hemangiomas, occur at any age but are more common in children and pregnant women. In children, these lesions typically present between the ages of 6 to 10 years and appear most commonly on the face and upper extremities.57 Congenital PGs exist but are rare. These small, red, glistening papules grow rapidly and bleed easily with trauma. Glucose transporter (GLUT)-1 staining can be used to

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distinguish them from infantile hemangiomas; PGs stain negative for GLUT-1, and infantile hemangiomas stain positive.58 PGs are thought to arise because of an unregulated angiogenic stimulus, but the exact pathogenesis is unknown. Trauma is commonly elicited as an inciting event, but other causes are being shown to contribute, including the use of certain systemic and topical drugs such as retinoids, 5-uoracil, granulocyte colony-stimulating factor, and some human immunodeciency virus protease inhibitors.59 PGs may also occur within a vascular malformation, such as a PWS, spontaneously or after laser treatment.60,61 If left untreated, these lesions will most likely persist and continue to cause bothersome bleeding. Treatment PGs, although benign, are often treated because they bleed easily and cause cosmetic concerns. They may mimic basal cell carcinomas and nodular melanoma, so it is essential to obtain biopsies for pathologic examination if malignancy is suspected. In children, skin cancer is a rare occurrence, so the prescribed treatment depends primarily on location, risk of scarring, and likelihood of recurrence. Surgical Surgical excision is the most common treatment prescribed because of the high recurrence rate of PGs. Full-thickness excision, shave excision, and curettage with or without cautery can effectively remove these lesions, but scarring, infection, and blood loss can occur. Full-thickness excision has been shown to result in a lower recurrence rate (2.9%) than other surgical methods such as curettage and electrocautery (715%).62 Laser Treatment with PDL or carbon dioxide (CO2) lasers is advocated in children with small PGs in cosmetically sensitive areas because of the low risk of scarring with lasers.57 Lee and colleagues62 reported recurrence rates of 0.43% after PDL treatment of PGs and 0.49% after CO2 laser vaporization.

Multiple (26) sequential PDL treatments are typically required for clearance, compared with a single CO2 laser vaporization procedure, but PDL treatments are easier for children to undergo because they are painless and have nominal postoperative recovery.63 Cryotherapy Although cryotherapy is an effective treatment with an acceptable side-effect prole and minimal scarring and dyspigmentation risk, it is not rst-line therapy for PGs because of its high lesional recurrence rates and number of treatments necessary. Lee and colleagues62 found a recurrence rate of 1.6% after cryotherapy, including patients treated multiple times. In a study by Mirshams and colleagues,64 18% of patients experienced resolution after one to four cryotherapy sessions. Topical Topical therapies are associated with high recurrence rates and are thus typically reserved for patients who refuse surgical and laser options. Silver nitrate cauterization can be used, but burning of unaffected skin is a common hazard.65 Use of topical phenol has also been reported, particularly in the treatment of periungual PGs, but multiple applications of a 98% solution are usually needed for clearance.66 A study reporting the use of imiquimod 5% cream demonstrated varied responses, including no lesional recurrence in some of the cases.67 Intralesional Sclerotherapy using intralesional injections of ethanolamine oleate, sodium tetradecyl sulfate, or polidocanol can lead to resolution of PGs but can cause cutaneous necrosis of the surrounding tissue.6870 Spider Angiomas Characteristics Spider angiomas, or nevus araneus, are commonly associated with high levels of estrogen, but they also appear in 15% of healthy preschool-aged children

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and 45% of school-aged children.3 Lesions are often seen on the dorsum of the hands, forearms, face, and ears, appearing as bright red papules or dilated vessels radiating from a central artery. Spider angiomas vary in size and often have surrounding erythema that can be blanched upon compression. Treatment Although spider angiomas are benign, they can be of cosmetic concern if they are present in a prominent location or are unusually large or numerous. Treatment with a PDL is the criterion standard, with only one or two laser sessions typically needed to remove them.71 (Figure 3A,B)

(A)

(B)

Other Vascular Lesions Venous Malformations Characteristics Venous malformations are present at birth and, instead of regressing over time, often become more noticeable. They appear clinically as soft blue nodules containing a mass of venules or as large, widespread abnormalities. Venous malformations may be supercial, resembling varicose veins, or deep.3 Blue rubber bleb nevus syndrome is a rare condition in which a person will have numerous venous malformations, most commonly involving the skin and the gastrointestinal (GI) tract. Although cutaneous venous malformations pose a cosmetic concern, GI venous malformations can lead to death due to GI hemorrhage.72 Treatment Venous malformations have traditionally been treated using surgical resection, sclerotherapy, and compression, but Nd:YAG laser treatment is now commonly used. Multiple laser sessions at 8- to 12-week intervals have been shown to reduce lesional color and bulk while improving dermal contour with minimal side effects. Small lesions are typically eradicated, whereas large venous malformations are reduced in size after multiple treatments.73 In addition to laser therapy, larger

Figure 3. Angioma before (A) and after (B) one neodymiumdoped yttrium aluminum garnet laser treatment.

malformations can be treated using percutaneous sclerotherapy with polidocanol microfoam and color Doppler ultrasonographic guidance.24 In blue rubber bleb nevus syndrome, cutaneous and mucocutaneous venous malformations have been similarly treated using Nd:YAG lasers.74 Yuksekkaya and colleagues75 successfully used sirolimus to shrink venous malformations in patients with multiple, potentially life-threatening lesions. Angiokeratomas Characteristics Angiokeratomas are characterized histologically by dilations of supercial dermal vessels and hyperkeratosis of the overlying epidermis.3 Angiokeratoma circumscriptum is a rare disorder, often presenting at

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birth, consisting of solitary or multiple angiokeratomas, usually occurring unilaterally on the lower extremities.76 Angiokeratoma corporis diffusum, or Fabry disease, is an X-linked inherited disorder caused by a deciency of the lysosomal enzyme alpha-galactosidase. This disease is characterized by angiokeratomas; irregularities in sweating; edema; scant body hair; painful sensations; and cardiovascular, gastrointestinal, renal, ophthalmologic, phlebologic, and respiratory involvement.77 Treatment Isolated angiokeratomas can be surgically excised, but this option may not be practical for conditions resulting in numerous lesions, such as angiokeratoma circumscriptum and Fabry disease. In these situations, laser therapy is commonly used. A variety of vascular-specic lasers have been used, including 532-nm Nd:YAG, 578-nm copper vapor, and 595nm PDL.77 Conclusion Physicians who evaluate and treat childhood vascular lesions should be familiar with the risks and benets associated with all available therapies. Treatment should be individualized for each patient based on known lesional response rates and available treatment options. The management of childhood vascular anomalies has advanced with the use of combination medical and surgical treatments, leading to greater clearance and minimal side effects. Additional studies are necessary to further enhance clinical outcomes.

5. Kawafuji A, Suda N, Ichikawa N, Kakara S, et al. Systemic and maxillofacial characteristics of patients with BeckwithWiedemann syndrome not treated with glossectomy. Am J Orthod Dentofacial Orthoped 2011;139:51725. 6. Schmidt D, Pache M, Schumacher M. The congenital unilateral retinocephalic vascular malformation syndrome (BonnetDechaume-Blanc syndrome or Wyburn-Mason syndrome): review of the literature. Surv Ophthalmol 2008;53:22749. 7. Alster TS, Tan OT. Laser treatment of benign cutaneous vascular lesions. Am Fam Phys 1991;44:54754. 8. Stier MF, Glick SA, Hirsch RJ. Laser treatment of pediatric vascular lesions: port-wine stains and hemangiomas. J Am Acad Dermatol 2008;58:26185. 9. Alster TS, Wilson F. Treatment of port-wine stains with the ashlamp-pumped pulsed dye laser: extended clinical experience in children and adults. Ann Plast Surg 1994;32:47884. 10. Nguyen CM, Yohn JJ, Huff C, Weston WL, et al. Facial portwine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser. Br J Dermatol 1998;138:8215. 11. Chapas A, Eickhorst K, Geronemus R. Efcacy of early treatment of facial port wine stains in newborns: a review of 49 cases. Laser Surg Med 2007;7:5638. 12. Rajaratnam R, Laughlin SA, Dudley D. Pulsed dye laser doublepass treatment of patients with resistant capillary malformations. Lasers Med Sci 2011;26:48792. 13. Huikeshoven M, Koster PH, De Borgie CA, Beek JF, et al. Redarkening of port-wine stains 10 years after pulsed-dye-laser treatment. N Engl J Med 2007;356:123540. 14. Kelly KM, Choi B, McFarlane S, Motosue A, et al. Description and analysis of treatments for port-wine stain birthmarks. Arch Facial Plast Surg 2005;7:28794. 15. Li L, Kono T, Groff WF, Chan HH, et al. Comparison study of a long-pulse pulsed dye laser and a long-pulse pulsed alexandrite laser in the treatment of port-wine stains. J Cosmet Laser Ther 2008;10:125. 16. Yang MU, Yaroslavsky AN, Farinelli WA, Flotte TJ, et al. Longpulsed neodymium:yttrium-aluminum-garnet laser treatment for port-wine stains. J Am Acad Dermatol 2005;52:48090. 17. Alster TS, Tanzi EL. Combined 595-nm and 1,064-nm laser irradiation of recalcitrant and hypertrophic port-wine stains in children and adults. Dermatol Surg 2009;35:9148. 18. Jasim ZF, Handley JM. Treatment of pulsed dye laser-resistant port-wine stain birthmarks. J Am Acad Dermatol 2007;57:67782. 19. Chang CJ, Hsiao YC, Mihm MC Jr, Nelson JS. Pilot study examining the combined use of pulsed dye laser and topical imiquimod versus laser alone for treatment of port wine stain birthmarks. Lasers Surg Med 2008;40:60510. 20. Tremaine AM, Armstrong J, Huang YC, Elkeeb L, et al. Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod. J Am Acad Dermatol 2012;66:63441. 21. Phung TL, Oble DA, Jia W, Benjamin LE, et al. Can the wound healing response of human skin be modulated after laser

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Address correspondence and reprint requests to: Tina S. Alster, MD, Washington Institute of Dermatologic Laser Surgery, 1430 K Street, NW Suite 200, Washington, DC 20005, or e-mail: talster@skinlaser.com

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