PEDIATRIC DERMATOLOGY Series Editor: Camila K. Janniger, MD Management of Cutaneous Hemangiomas in Pediatric Patients Maria Letizia Musumeci, MD, PhD; Karina Schlecht, MD, PhD; Rosario Perrotta, MD; Robert A. Schwartz, MD, MPH; Giuseppe Micali, MD Cutaneous hemangiomas (CHs) are common benign during the first year of life and slow involution that vascular tumors of childhood. Clinically, they are usually is completed by 5 to 10 years of age.1 For characterized by a typical evolution profile, consist- this reason, no treatment is necessary in most cases. ing of a rapid proliferation during the first year of However, when CHs are located in areas at risk for life and slow involution that usually is completed functional complications; are of considerable size; or by 5 to 10 years of age. In most cases, no treat- repeatedly undergo bleeding, ulceration, or superin- ment is necessary. However, when CHs are located fection, a prompt and adequate treatment approach in areas at risk for functional complications; are of is required.2 considerable size; or repeatedly undergo bleeding, ulceration, or superinfection, a prompt and adequate Epidemiology treatment approach is required. First-line approaches CHs are present in 1.0% to 2.6% of neonates and in include topical, intralesional, and systemic corti- 10% to 12% of infants by 12 months of age.3 Thirty costeroids. Second-line options include interferon percent of CHs are first evident at birth; the remain- alfa-2a and -2b, laser therapy, and surgical therapy. der appear during the second month of life. The Third-line approaches include cytotoxins, emboliza- frequency of these benign tumors increases in pre- tion, and angiogenesis inhibitors. Other therapies term infants, and the female to male ratio is variable and procedural approaches including intermittent from 2:5 to 4:1.4,5 In a study of 578 infants exposed pneumatic and continuous compression; cryosurgery; to chorionic villus biopsy, the incidence of CHs was radiotherapy; implantation of copper needles; sclero- approximately 21%.6 therapy; electrocautery; electroacupuncture; imiqui- mod cream 5%; and prospective agents, such as Clinical Assessment OXi4503 (diphosphate prodrug of combretastatin A1) In general, CHs are solitary (80% of cases), mea- and cidofovir, are discussed. Treatment options for suring approximately a few millimeters to 5 cm in ulcerated CHs also are described. size; less frequently, multiple tumors are present or Cutis. 2008;81:315-322. larger in size.7 Although every part of the body may be affected, the head and neck are involved in utaneous hemangiomas (CHs) are common 60% of cases.8,9 benign vascular tumors of childhood. Clini- The appearance of CHs depends on their location C cally, they are characterized by a typical within the cutis (superficial, deep, or mixed [superfi- evolution profile, consisting of a rapid proliferation cial and deep]). CHs are classified into localized and segmental forms. Localized forms generally are small, Accepted for publication July 26, 2007. Drs. Musumeci, Schlecht, and Micali are from the Department of whereas segmental CHs display a linear distribution Dermatology and Dr. Perrotta is from the Department of Plastic and/or well-demarcated shapes resembling islands on Surgery, all from the University of Catania, Italy. Dr. Schwartz a map covering larger anatomic regions.10 is from Dermatology and Pediatrics, New Jersey Medical Medical history and physical examination are School, Newark. sufficient to diagnose CHs in 95% of cases.11 The authors report no conflict of interest. Correspondence: Giuseppe Micali, MD, Clinica Dermatologica, Normally, CHs are asymptomatic but can lead to Università di Catania, Piazza Sant’Agata La Vetere, 6, 95124, serious or even life-threatening complications in Catania, Italy ([email protected]). rare instances. VOLUME 81, APRIL 2008 315 Pediatric Dermatology Sites associated with complications include air- safe if used cautiously under medical supervision. ways, eyes, and the lumbosacral region.12 Infants The patient should be warned of adverse reac- with mandibular and neck CHs in a beard distribu- tions such as cutaneous atrophy and striae.25 tion and patients presenting with crouplike cough Betamethasone dipropionate ointment 0.05%, should be closely observed for respiratory distress clobetasol propionate 0.05% ointment or cream, and evaluated with direct laryngoscopy if needed.13 and halobetasol propionate 0.05% ointment or Periocular CHs may have an adverse impact on the cream have been successfully used.26 visual axis. Obstruction of the visual axis results in Intralesional corticosteroids, such as triamcin- stimulus deprivation–induced amblyopia.14 Pressure olone acetonide, can be employed for well-defined on the cornea can lead to astigmatism, which can and low-risk CHs during the proliferative phase to cause permanent amblyopia. Other ophthalmic com- restrict growth and hasten involution. They may be plications associated with periocular CHs include injected for small lesions (1–2 cm in diameter) on tear duct obstruction, proptosis, ptosis, strabismus, the lips, nasal tip, cheeks, or ears (2–5 intralesional and myopia.14 Infants with periocular lesions should injections at 4–8-week intervals with concentra- undergo immediate ophthalmologic evaluation. tion of 10–20 mg/mL, administered in doses of up to Patients with lumbosacral CHs should be evalu- 3–5 mg/kg per treatment session).20,25 One injection on ated for spinal dysraphism, tethered cord syndrome, each visit is administered as needed. They should be used and genitourinary anomalies. Initially, infants with caution for periocular CHs because of rare compli- may be asymptomatic, but progressive neuro- cations, such as retinal artery occlusion, eyelid necrosis, logic damage will occur if the tethered spinal temporary eyelid dyspigmentation, and subcutaneous cord is not released. Spinal dysraphism includes fat atrophy.25,27 The suggested treatment regimen is a anomalies such as abnormal genitalia, rectal 50:50 mix of triamcinolone acetonide (40 mg/mL) and fistulas, and anorectal and renal abnormalities.15,16 betamethasone acetate (6 mg/mL) per treatment every CHs in association with other anomalies include 4 to 6 weeks,27-29 and reported side effects include cuta- PHACE syndrome (posterior fossa malformations, neous atrophy and pain during injection. The response hemangiomas, arterial anomalies, coarctation of the rate for administration of intralesional corticosteroids aorta and cardiac defects, and eye abnormalities) may be similar to systemic therapy. and hemangiomatosis.17-19 Benign and disseminated Systemic corticosteroids are the mainstay of neonatal hemangiomatosis are 2 distinct categories of therapy for larger, deforming and endangering, or disease characterized by multiple CHs. life-threatening lesions, and usually are indicated Ulceration is the most frequent complication of during their proliferative phase (Figure 1).30,31 CHs and can lead to infection, bleeding, pain, and Oral prednisone or prednisolone can be con- scarring. Infants with CHs should be followed closely, sidered and should be tailored to the patient’s especially during the proliferative phase when prob- response at dosages from 2 to 4 mg/kg daily for lematic ulceration is most likely to occur.20 2 to 3 months and then gradually tapered over several months.30 This dosage must be main- Management and Treatment tained until the functional risks determined by The goals of managing patients with CHs are preven- the CHs subside. Stopping treatment before ade- tion of life- or function-threatening complications quate therapeutic response may result in rebound (eg, obstructed airways, impaired vision) or perma- growth. If no response is noted within 3 to nent disfigurement because of residual postinvolution 6 weeks, the therapy should be discontinued.30 skin changes (eg, nasal hemangioma, large facial Considerably large CHs, with fast growth and lesions); prevention or treatment of ulceration to atypical behavior, may require higher dosages (up minimize infection, bleeding, pain, or scarring; and to 8 mg/kg daily).32 In some cases, the simulta- avoidance of aggressive or scarring treatments.21,22 neous injection of intralesional corticosteroids CHs of infancy can have a great psychological may be particularly advantageous. Approximately impact on patients and their parents23,24; therefore, 35% of patients will develop complications from education plays an important role in the manage- prolonged use, including irritability, delayed skel- ment of this condition. Regular follow-up visits etal growth, hypertension, immunosuppression, are needed to provide continuous reassurance and cushingoid appearance, and adrenal suppres- monitor the course of the lesion. sion.33,34 The use of prophylactic oral ranitidine First-Line Therapy—First-line therapies for CHs hydrochloride (2–4 mg/kg once daily to a maximum include topical, intralesional, and systemic corti- of 150 mg/d) or cimetidine hydrochloride (20 mg/kg costeroids. Topical corticosteroids can be used for per day) to prevent gastritis from systemic cortico- low-risk CHs and are efficacious and relatively steroids is recommended.25,31,34 316 CUTIS® Pediatric Dermatology A B Figure 1. Mixed-type (superficial and deep) cutaneous hemangioma of the upper eyelid before (A) and after 10 weeks of systemic corticosteroid therapy (B). Reprinted with permission from Musumeci et al.31 Upon completion of treatment with cortico- recommendations suggest the treatment of an steroids,