Central Journal of Dermatology and Clinical Research

Review Article *Corresponding author Marcia Hogeling, Department of Dermatology, UCLA Medical Center, USA, Tel: 310-917-3376; Fax: 310-582- Infantile Hemangioma: A Brief 6302; Email: Submitted: 17 May 2016 Review of Clinical Manifestations, Accepted: 20 July 2016 Published: 22 July 2016 Copyright Associations and Treatment © 2016 Hogeling et al.

Laura Obler and Marcia Hogeling* OPEN ACCESS Department of Dermatology, UCLA Medical Center, USA Keywords • Infantile hemangioma Abstract • Vascular tumor Infantile hemangiomas (IH) are the most common vascular tumors in children, occurring • PHACE syndrome in 4-5% of infants. They are benign and usually require no treatment because they regress • LUMBAR syndrome spontaneously in the first few years of life. Infants with large segmental IH or those with • Intrahepatic infantile hemangioma multifocal presentations should have further imaging to rule out structural anomalies or • Propranolol hepatic involvement. In recent years, oral propranolol has become the first line treatment for complicated IH, supplanting the need for corticosteroids, lasers, and excision in many cases. It can be used to halt growth and cause regression in IH that are at high risk for developing complications, including ulceration, disfigurement, or impairment of essential functions (e.g. vision or breathing). Early referral to a Pediatric Dermatologist is imperative since treatment is most effective when started before complications develop.

INTRODUCTION weight, prematurity, and placental anomalies (which are often Infantile hemangiomas (IH) are the mostcommon vascular non-Hispanics are more likely to develop IH [3], and low birth tumors in children, occurring in 4-10% of infants [1]. They Drolet et al., showed that for every 500 gram decrease in birth are benign growths of endothelial cells that are often easily associated with one another) are additional risk factors [4]. diagnosable by history and physical examination and usually require no treatment because they regress spontaneously in the weight, there is a 40% chance increased risk of IH [5]. which appears as a patch of ecchymosis, pallor or telangiectasias, mayIH be are present not fully [6]. formed IH typically at birth, proliferate but a premonitory rapidly during mark, the orfirst impairment few years of of life. essential In some functions cases, however, (e.g. vision the or location breathing). and Certainmorphology types of of the IH lesion are associated can cause with ulceration, congenital disfigurement, structural first 2 to 3 months, with one study demonstrating that the most developing complications or associated with structural defects is growth, especially for superficial IH, occurs between 5.5 and 7.5 weeks of life [6]. IH reach 80% of their maximum size on average abnormalities. Early identification of lesions that are high risk The for pathogenesis of IH is still under investigation, but angiogenesis by 3 months; however, the mean age of visit with a specialist andimportant vasculogenesis for determining are two proposed further workup mechanisms. and treatment. Hemangioma aroundis not until one 5 year months of age of age and [7]. begins Deep to IH spontaneously may have a prolonged involute, stem cells, which are primitive mesenchymal cells that can be growth phase [8]. After rapid proliferation the tumor stabilizes isolated from proliferating IH, are one cell type implicated in [9]. vasculogenesis. These cells show self-renewal properties and in with maximum involution usually occurring by 3.5 years of age DIAGNOSIS AND CLINICAL MANIFESTATIONS cultures can differentiate into cell types found in IH, including endothelium, adipocytes, and pericytes. Furthermore, when Most IH can be diagnosed with a complete history and physical transplanted into mice, they cause de novo vessel formation examination. The differential diagnosis includes vascular tumors, [2]. Infantile hemangiomas are positive for GLUT 1(Glucose vascular malformations, and other neoplasms (Table 1) [10]. Congenital hemangioma, a rare vascular tumor that is included in distinguish it from other vascular tumours and is also found on the differential of IH, is distinguishable from IH in that it is fully placentalTransporter cells. 1), Hypoxia an immunohistochemical may play a role in IH development, marker that which helps formed at birth. These lesions often present as exophytic masses or plaques, often with a halo of pallor, and have two major weight and prematurity. subtypes: non-involuting and rapidly involuting. IH can be single may explain risk factors associated with IH, such as low birth or multiple and are found anywhere on the body but are most RISK FACTORS AND NATURAL HISTORY

commonly on the head and neck [11]. IH can be subdivided into Several risk factors have been identified. Females and white, superficial, deep or mixed presentations [12]. Superficial IH are Cite this article: Obler L, Hogeling M (2016) Infantile Hemangioma: A Brief Review of Clinical Manifestations, Associations and Treatment. J Dermatolog Clin Res 4(3): 1076. Hogeling et al. (2016) Email: Central

Table 1: Differential Diagnosis of IH [10]. Vascular Tumors and Malformations Other benign tumors Malignant Tumors Congenital Hemangioma Juvenile xanthogranuloma - rapidlyinvoluting Pilomatricoma Neuroblastoma - partiallyinvoluting Rhabdomyosarcoma - non-involuting Infantile hemangiopericytoma Tufted angioma SolitaryInfantile reticulohistiocytoma myofibroma DermatofibromaLymphoblastic sarcoma lymphoma protuberans Pyogenic granuloma Lipoblastoma Giant cell fibrosarcoma Kaposiformhemangioendothelioma Sacral lipoma Peripheral primitive neuroectodermal tumor Spindle cell hemangioma Encephalocele/meningocele Congenital leukemia cutis Congenital eccrineangiomatoushamartoma Heterotopic brain tissue Capillary malformation Dermoid cyst Adrenocortical carcinoma Venous malformation Angiosarcoma Glomuvenous malformation Lymphatic malformation LangerhansPlexiformneurofibroma cell histiocytosis Combined vascular malformation (Klippel-Tre- Spitz nevus naunay syndrome)

VerrucousHereditary “hemangioma” hemorrhagic and telangiectasia angiokeratoma MultifocalArteriovenous lymphangioendotheliomatosis malformation

(Figure 1). Deep IH are paler, blue-tinged nodules that are often larger.bright pinkDeep or IH red, tend minimally to present raised at later papules, ages plaques, and involute or nodules more slowly than superficial IH [7] .Mixed presentations are common andIn have addition both superficial to depth of and tumor, deep IH components can be described [12] (Figure as focalor 2). papule, or plaque and appear to arise from an isolated point. Segmentalsegmental IH (a.k.a. are often regional).Focal plaques and occupy IH form a larger a solitary subunit nodule, of the body, such as part of the face or extremity. Segmental IH are more Figure 2 Deep infantile hemangioma. found on the head or lumbosacral areas, they may be associated likely than focal IH to develop complications [13] (Figure 3). If with underlying extracutaneous structural anomalies (PHACE syndromePHACE AND and LUMBAR LUMBAR syndrome, SYNDROMES respectively) [14,15]. includes large segmental IH of the face and associated structural PHACE syndrome is a neurocutaneous syndrome that fossa brain malformations, hemangioma, arterial anomalies, cardiovascular/aorticanomalies. PHACE is anomalies, an acronym and thateye abnormalities. stands for posterior Ventral midline defects, such as sternal defects, are also associated. Figure 3 Segmental infantile hemangioma.

Definite diagnosis of the syndrome requires a segmental facial or scalp IH (at least 5cm wide) and one major anomaly. In one study,

20% of patients with segmental facial hemangiomas had PHACE echocardiography,syndrome [14]. Work-up and ophthalmology for infants with assessments segmental IH to of evaluate the face foror scalpthe presence should includeof associated MRI brain,anomalies. MRA of the head and neck,

large segmental IH of the lower body and associated structural Similar to PHACE syndrome, LUMBAR syndrome includes other cutaneous defects, urogenital anomalies, ulceration, myelopathy,anomalies. LUMBAR bony stands deformities, for lower anorectal body hemangioma malformations, and

Figure 1 syndrome may require extensive diagnostic imaging to detect arterial anomalies, and renal anomalies. Children with LUMBAR Superficial infantile hemangioma. J Dermatolog Clin Res 4(3): 1076 (2016) 2/4 Hogeling et al. (2016) Email: Central age with lower body segmental IH should have ultrasound of the proliferation of stem cells and promotes apoptosis [25]. Side and monitor anomalies, but all children less than 3 months of effectscAMP levels of oral and propranolol increased are MAPK rare signaling, butinclude which bradycardia, reduces such as spinal dysraphism [15]. hypoglycemia, hypotension, acrocyanosis, and diarrhea [24,26]. spine, abdomen, and pelvis to look for common malformations, MULTIFOCAL IH it a viable option for treating IH that are not just functionally IH can have a multifocal presentation, in which there are many The relative efficacy and safety of using propranolol has made small, local IH. The tumors can be similar in appearance or vary threateningPropranolol but also appears pose his to risk be effective for disfigurement throughout or ulceration. all stages visceral involvement, and a common site for extracutaneous IH is in size and shape. Multifocal presentations can be associated with the liver. Intrahepatic IH follow a similar course as cutaneous IH, reduceof tumor complications development, of unlikeIH, propranolol corticosteroids, should whichbe started are early most with proliferation and involution growth phases. They are benign effective during the proliferative stage [23]. However in order to failure, hypothyroidism, and abdominal compartment syndrome for IH that are high risk. Doses are usually between 1 and 3 mg/ tumors; however, if there are extensive intrahepatic IH, heart are possible complications. One prospective study showed that age,kg/day pre-existing divided over concern two doses, for hypoglycemia, and initiation cardiovascular may occur as an or 16% of children with 5 or more IH had hepatic hemangiomas [16]. respiratoryinpatient for comorbidities, infants with less or inadequate than 8 weeks social corrected support. gestational Inpatient Therefore, screening abdominal ultrasonography is indicated in infants younger than 6 months of age with 5 or more cutaneous syndrome and cerebrovascular anomalies, due to the theoretical IH to evaluate for hepatic involvement. initiation is recommended for high risk patients with PHACE COMPLICATIONS for patients with bradycardia. Other therapies for IH include risk of stroke [27]. Pretreatment electrocardiograms can be done steroids, and excision. These are less commonly used than oral treatment, 24% of IH seen at tertiary centers may develop topical timolol, pulsed-dye laser, [28] intralesional or topical Although most IH regress spontaneously without requiring IH [29]. Fully formed pedunculated IH that will ultimately leave propranolol. Topical timolol may be effective for small superficial complications [13]. Ulceration is the most frequent complication regions.and is more Ulcerations likely to can occur lead on to segmental pain, super IH infection, and areas and with scarring high prominent residual fibro fatty tissue or persistently ulcerated IH friction or moisture, commonly the neck, lips, and anogential maySUMMARY be treated by excision [10,30]. andOther are more complications often treated include than non-ulcerating functional impairment IH [17]. and/or IH are common tumors in children that often require no treatment. Infants with large segmental facial or lower extremity visual complications, such as astigmatism or amblyopia, due to IH or those with multifocal presentations should have further disfigurement due to location of the IH. Periorbital IH can cause imaging to rule out structural anomalies or hepatic involvement. involvement can cause airway obstruction and require systemic Indications for treatment include tumors that are threatening and/orpressure surgical on the globe treatment.IH or visual field on obstruction. the central IH face, with nasallaryngeal tip, vital functions (vision or breathing), located in places at high pinna, or eyelids can involute leaving destruction of anatomical Dermatologist is imperative since treatment is most effective telangiectasia [9]. whenrisk for started disfigurement, before complications or ulcerating. develop. Early referral Oral propranolol to a Pediatric is structures, residual fibrofatty tissue, scars, anetoderma, or TREATMENT now considered first line for treating IH, with several recent trials indicating its safety and efficacy. More research needs to be done oral corticosteroids, with interferon alpha and vincristine used comparing safety and efficacy of different topical and systemic for Prior refractory to 2008, cases, treatment and intralesional options for steroids IH were and limited surgical to betaREFERENCES blockers. of the adverse effects of corticosteroids, [21] treatment was 1. Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? reservedexcision performedfor tumors that in certain threatened situations vital functions [9,18-20]. (e.g. Because vision et al., discovered the A systematic review of the medical literature. Pediatr Dermatol. 2008; effectiveness of oral propranolol in treatment of severe IH 2. 25:Greenberger 168-173. S, Bischoff J. 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Cite this article Obler L, Hogeling M (2016) Infantile Hemangioma: A Brief Review of Clinical Manifestations, Associations and Treatment. J Dermatolog Clin Res 4(3): 1076.

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