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Infantile hemangiomas (IHs) are the most benign vascular tumors of infancy. IHs occur in 10–12% of infants. They often appear within 1–4 weeks of life. Superficial lesions are bright red or “strawberry” in color, sharply demarcated papules, nodules or plaques. Deep lesions are of bluish hue and dome-shaped. IHs are described as localized or focal, segmental, indeterminate or multifocal pattern, depending on the anatomic appearance. Segmental lesions are often associated with complications. High-risk IH groups which have severe complications can be observed in IHs with disfigurement, life-threatening complications, functional impairment, ulceration and associated structural anomalies; PHACE syndrome (Posterior fossa brain malformations and large facial hemangiomas, Hemangiomas of the cervicofacial region, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, Sternal cleft and supraumbilical raphe) and LUMBAR syndrome (Lower body hemangioma often extending onto a unilateral lower extremity, Urogenital anomalies, ulceration, Myelopathy, Bony deformities, Anorectal malformations, arterial anomalies and Renal anomalies). Early treatment is vital to avoid complications in high-risk IHs. The presence of segmental IH larger than 5 cm on face, scalp or cervical region is the major sign of PHACE syndrome, whereas segmental IHs affecting the lower body are the significant signs of LUMBAR syndrome.
Department of Hematology and Oncology, Ankara University Medical School, Ankara, Turkey
*Address all correspondence to: sgozdasoglu@hotmail.com
1. Introduction
Infantile hemangiomas (IHs) are vascular birthmarks and represent the most common benign vascular tumors of infancy. Virchow used the term “angioma” to describe all vascular anomalies. The word “hemangioma” is derived from the ancient Greek word “haima” meaning blood [1]. In 1982, the first biological classification of vascular birthmarks was proposed by Mulliken and Glowacki who divided these lesions into two groups: hemangiomas and vascular malformations [2]. The new classification by the International Society for the Study of Vascular Anomalies (ISSVA) was published in 2018, according to which vascular anomalies are separated into two major categories: the first is vascular tumors and the second is vascular malformations. Vascular tumors are associated with proliferative changes of endothelial cells (ECs) and vascular malformations primarily consisted of structural vascular abnormalities [3]. Infantile hemangiomas are the most common benign vascular tumors, rapidly growing during the first year of life and subsequently involuting. In the literature, the articles on the clinical characteristics of IHs, advancement in treatment approaches and the studies on pathogenesis increased remarkably. Frieden published an article detailing the increase of the articles on the issue between 1960 and 2009 in a chronological order (Figure 1) [4]. Leung et al. reviewed meta-analyses, randomized controlled trials, clinical trials, observational studies and reviews by PubMed search which were published in the past 20 years and reported the clinical evaluation of IHs, risk factors and congenital abnormalities which are seen with IHs, diagnostic and differential diagnosis criteria and treatment approaches [5]. Lin et al. recently evaluated for the first time the bibliometric analyses specifically focusing on IHs publications. A total of 4333 articles and reviews on IHs were collected from Web of Science (WoS) database from 2000 to 2022. The United States has the highest number of publications, the highest total number of citations and the largest number of scientific research institutions and IH researchers, leading most of the cross-country collaborations. The top five countries with the most publications on IHs are given as follows: USA, China, Italy, United Kingdom and Japan. Although China is ranked as the second country regarding published articles on this issue, the number of citations is low. The top three most influential authors were Frieden, Mulliken and Drolet. The articles published by Léauté-Lebrèze in 2008 had the highest number of citations. A certain research foundation for this field was laid by the articles published by North PE in 2000 and Boye E in 2001 [6].
Figure 1.
Results of a PubMed search on August 1, 2011 (used with permission of Frieden).
In this chapter, my main objective is twofold: to review the pathogenesis of IHs and to analyze clinical presentations, risk factors, complications of IHs and hemangioma-related syndromes. The treatment of infantile hemangiomas is excluded in this chapter.
The incidence of IHs is estimated to be 1.1–2.6% in neonates and 10–12% in infants by the first year of life [5, 7]. IHs develop more commonly in female infants. The female-to-male ratio is approximately 3:1–5:1 [5, 8]. Ding et al. reported the results of the meta-analysis of the published studies of potential risk factors for IHs. According to this meta-analysis, risk factors, such as preterm birth, low birth weight, female gender, multiple gestation, progesterone therapy and family history, may affect the appearance of IHs [9]. Additionally, twins, white ethnicity, increased maternal age, preeclampsia, placental anomalies (such as placenta previa, placental abruption and abnormal insertion of the umbilical cord), in vitro fertilization, maternal vaginal bleeding during the first trimester, gestational diabetes mellitus, gestational hypertension, invasive antepartum procedures (such as amniocentesis and chorionic villus sampling), perinatal hypoxia and mechanical stress during delivery may also have an effect on the occurrence of these lesions [5, 8]. On the other hand, Blei et al. identified six kindreds where hemangiomas appear to segregate as an autosomal dominant trait with high penetrance. A linkage to a locus on chromosome 5q31-33 has been identified in genetic mapping of a novel familial form of infantile hemangioma based on recombination breakpoint analyses by the same researchers [10, 11].
The International Society for the Study of Vascular Anomalies (ISSVA) classification has provided a better understanding of the terminologies, biology and clinical characteristics of vascular tumors and vascular malformations. The ISSVA classification is shown in Table 1. Vascular anomalies were classified into two large categories: vascular tumors and vascular malformations [3]. Vascular malformations, which include capillary, lymphatic, venous and arterial vessel formation, are described as congenital developmental disorders [12, 13]. Whereas vascular tumors are characterized by endothelial cell hyperproliferation, typically lesions grow rapidly and most of them are not present at birth [13]. Vascular tumors are classified as benign, locally aggressive or borderline and malignant [3].
The pathogenesis of IHs is complex and poorly understood. There are many researches that aim to have a better understanding of the pathogenesis of IHs in the literature and several hypotheses have been proposed. Scientists have suggested that IHs are a result of dysregulated vasculogenesis and angiogenesis. Angiogenesis and vasculogenesis are regulated by many important signaling pathways, such as vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) pathway, Notch pathway, β-adrenergic signaling, hypoxia-inducible growth factor-α (HIF-α)-mediated pathway, etc. These pathways have been linked to each other by several interactions in the development of angiogenesis and vasculogenesis [14, 15].
Placental growth factor (PIGF), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B), vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D) are members of the human vascular endothelial growth factor (VEGF) family that plays pivotal roles in embryonic development and angiogenesis-dependent disease [15]. The functions of the VEGF family members are defined by their receptors’ specificity. Two receptors for VEGF (VEGFR-1 and VEGFR-2) which play the regulation of angiogenesis are located on endothelial cells, bone marrow-derived hematopoietic cells and tumor cells. They are also members of the tyrosine-kinase family. The expression of these receptors is low in normal tissues [15]. Boscolo et al. reported VEGF-A levels in serum samples were found to be significantly higher in proliferating compared to involuting phases [16].
The first hypothesis is the somatic mutation of hemangioma stem cells and upregulation of vascular endothelial growth factor receptor (VEGFR) signaling pathway. Hemangioma stem cells (HemSCs) and hemangioma endothelial cells (HemECs) are the two most important cells in the pathogenesis of IHs. Hemangioma stem cells have the ability to undergo self-renewal and can differentiate into HemECs, pericytes and adipocytes (Figure 2).
Figure 2.
Multipotent hemangioma-derived stem cells (HemSCs) differentiate into HemECs, pericytes and adipocytes. HemSCs play an important role in the pathogenesis of IHs (adapted from Ref. [16]. Used with permission of Boscolo).
Infantile hemangiomas have three characteristic phases:
Proliferating phase, it is characterized by the proliferation of a large number of HemECs. Hemangioma stem cells mainly differentiate into HemECs and pericytes to promote angiogenesis.
Involuting phase, HemSCs mainly differentiate into adipocytes, inhibiting the proliferation of HemECs.
Involuted phase, the tumor is replaced by fat and/or connective tissues in this phase [14, 15, 16].
Khan et al. investigated to determine whether HemSCs would form hemangiomas in immunodeficient nu/nu mice. When implanted subcutaneously into nude mice, HemSCs can produce the erythrocyte-type glucose transporter 1 protein (GLUT-1) positive microvessels at 7–14 days. Hemangioma stem cells form hemangioma-like GLUT-1 positive blood vessels in nude mice [17]. This study identified a stem cell as the cellular origin of IHs.
Boscolo and Bischoff recognize that IHs may not only be a disorder of angiogenesis (i.e., the formation of new blood vessels from existing vessels) but also—at least in part—a disorder of vasculogenesis (i.e., the de novo formation of new blood vessels from cells) [16].
The second hypothesis is the placental theory which proposes that a fetal placental progenitor cell is the cell type of origin for IHs. North et al. published an article that identified the marker GLUT-1 as a specific feature of IHs during all phases of these lesions. The GLUT-1 is highly expressed in human brain and placenta but not in normal skin or subcutaneous tissue. GLUT-1 immunoreactivity, which is a highly selective and diagnostically useful maker for IHs, was not found in any of the vascular malformations in this research [18]. Placenta-associated antigens, which are Fc gamma receptor II (Fc-gamma-RII), Lewis Y antigen (LeY), merosin and GLUT-1, are expressed in an infantile hemangioma (IH). Infantile hemangioma might also originate from embolized placental tissue [18, 19]. Mihm Jr. et al. suggested that the hemangioma precursor cell comes from the placenta as a “benign metastasis” [20].
The third hypothesis is the tissue hypoxia-induced vascular proliferation theory. Hypoxia is one of the most powerful inducers of angiogenesis and vasculogenesis by stimulating the expression of angiogenic factors, such as VEGF-A and basic fibroblast growth factor (bFGF), on endothelial progenitor cells. Many of the conditions such as preterm birth, low birth weight, preeclampsia and placental anomalies, which predispose an infant to development of IHs, are associated with hypoxia. It is believed that hypoxia stimulates the release of hypoxia-inducible factor-1α (HIF-1α) which promotes the production of VEGF [15, 16].
Hypoxia-inducible factor-1α (HIF-1α) is expressed significantly high in HemECs than normal in endothelial cells (ECs). It is also a significant contributor to the elevated VEGF levels produced in HemECs when it is upregulated. The decreased expression of HIF-1α reduces the proliferation of these cells [15].
MicroRNA (miRNA) and long noncoding RNAs (IncRNAs) also affect the profileration, migration and apoptosis of HemECs. The chromosome 19 miRNA cluster (C19MC) are expressed both in the placenta and in IH endothelial cells, but are not in other vascular anomalies and in the control group of healthy infants. A correlation with the tumor size and clinical response to treatment is demonstrated by circulating C19MC microRNA levels. This is the first potential biomarker for IHs [14].
The fourth hypothesis is the renin-angiotensin system theory. Itinteang et al. reported that IH endothelial cells in the proliferative phase express angiotensin-converting enzyme (ACE) and angiotensin II-receptor-2 (ATII-receptor-2), both integral components of the renin-angiotensin system. According to their hypothesis, the high serum levels of renin lead to a high concentration of angiotensin II [21]. Both angiotensin II and angiotensin II-receptor-2 upregulate VEGF that activates the proliferation of IHs-derived blast cells. The expression of ACE and ATII-receptor-2 on the endothelium of proliferating IH supports this theory [21]. Tan et al. reported that β-adrenergic blockers may be associated with the blocking of β1-adrenergic receptors in the kidney, leading to the inhibition of renin release in the accelerated involution of IH [21, 22]. The spontaneous involution that occurs in IH may be related to decreasing serum renin levels with age and/or depletion of the endothelial progenitor cells with time [23]. Interactions between proposed theories of infantile hemangioma pathogenesis are shown in Figure 3.
Figure 3.
Interactions between proposed theories of infantile hemangioma pathogenesis. * IGF-2, insulin-like growth factor (adapted from Ref. [23]. Used with permission of Forbess Smith).
Most of the lesions are developed in the skin and subcutaneous tissues. These are hypervascular, multinodular patterns that are composed of hyperplastic endothelial cells, pericytes and prominent basement membranes (Figures 4 and 5) [24, 25].
Figure 4.
The image shows lobular growth pattern of infantile hemangioma -a common form of capillary hemangioma (from WebPathology.com).
Figure 5.
Plump endothelial cells line with and without lumens in the early phases of the lesions (from WebPathology.com).
Glowacki et al. reported that hemangiomas in the proliferative phase contained large numbers of mast cells in comparison with hemangiomas in the involution phase. Mast cells may have an important role in the development of IHs [26]. Dilated vascular lumens and flattened endothelial cells are observed in the involution stage [24]. Placenta-associated antigens staining, including FcRII, Lewis Y antigen (LeY), merosin and GLUT-1, is expressed in an IH [19, 20]. Infantile hemangiomas express GLUT-1 during all phases of their development (Figure 6).
Figure 6.
The endothelial cells of infantile hemangiomas consistently express GLUT-1+, which is a brown colored protein in the endothelial cells, a glucose transport receptor (image courtesy of: Marta Garrido, MD, Barcelona, Spain; from WebPathalogy.com).
GLUT-1 immunoreactivity is a highly selective useful marker for diagnosis [18].
Infantile hemangiomas are clinically heterogeneous by their appearance in regard to superficially, depth, location and stage of evaluation. Infantile hemangiomas have a triphasic evaluation.
Proliferative phase: infantile hemangiomas (IHs) grow rapidly in the first 3 months of life but occasionally the proliferative phase may continue up to 12 months of age. The lesion is stable between 6 and 12 months in plateau period.
Involution phase: this phase begins around 1 year of age and continues for 3–5 years. Approximately 50% of IHs will show complete involution by the time a child reaches age 5.
Involuted phase: this phase is reached by 5–8 years of age but sometimes up to 10 years of age. The tumor sometimes is replaced by fat and/or connective tissues [14].
In the newborn, hemangiomas may originate as a pale macule with thread-like telangiectases [7]. They often appear within 1–4 weeks of life [8, 27]. Two types of skin lesions, namely “superficial” and “deeper,” can be seen in IHs. Bright red or “strawberry” in color, raised, sharply demarcated, firm papules, nodules or plaques are observed as superficial lesions. Deeper lesions may appear as a skin-colored nodule or can have more of a bluish hue [7, 23]. Mixed lesions in which both epidermis and deeper subcutaneous tissues are involved were also reported in some cases [23].
On the other hand, depending on the anatomic appearance IHs are described as localized or focal, segmental, indeterminate or multifocal pattern. Localized or focal IHs are the most common pattern, well-circumscribed focal lesions appearing to rise from a point while segmental IHs are plaque-like extensive IHs measuring 5 cm in diameter. Segmental IHs may be associated with extracutaneous manifestations. Indeterminate IHs are not clearly localized or segmental and are often called partial segmental, whereas multifocal IHs are multiple discrete IHs located at multiple distant sites [28].
Hemangiomas are usually solitary with a size range from a few millimeters to several centimeters in diameter. Approximately 20% of cases have multiple lesions [7]. Approximately 60% of IHs are superficial, 15% deep and 25% mixed—superficial and deep (Figures 7 and 8) [29, 30].
Figure 7.
A 4-month-old girl with a superficial infantile hemangioma on the face.
Figure 8.
Infantile hemangioma on the mandibular segment and cardiac failure in a 1-month-old girl.
Head and neck are primary regions where IHs are most frequently located. These are followed by the trunk 25% and the extremities 15%. IHs rarely develop in the intestinal organs, such as the liver, gastrointestinal tract, respiratory tract, urinary tract and central nervous system [8]. Hepatic hemangiomas can be identified as focal, multifocal or diffuse types. Kulungowski et al. investigated that cutaneous hemangiomas are associated with multifocal hepatic hemangioma, diffuse hepatic hemangioma and focal hepatic hemangioma. Hypothyroidism was determined in all the patients with diffuse hepatic hemangioma, 21.4% with multifocal hepatic hemangioma but it was not recognized in any of the patients with focal hepatic hemangioma [31]. Hypothyroidism can be observed due to inactivation of the thyroid hormones by type 3 iodothyronine deiodinase (D3) in the tumor tissue [32].
Infantile hemangioma can be linked to particular congenital organ malformations. Blei et al. reported an infant girl with cutaneous facial and upper trunk hemangioma accompanied supraumbilical midabdominal raphe and sternal atresia. This association is the first report in the dermatologic literature [33]. In 1996, Frieden et al. reported two patients who had large facial hemangioma, congenital cataracts, and structural arterial abnormalities, particularly of the central nervous system vasculature. The authors thought that large >5 cm particularly facial hemangiomas associated with these anomalies are a distinct group and referred to as the “PHACE syndrome” for this association [34].
A 1-month-old infant (Figure 8) was admitted to our intensive care unit (ICU) with difficulty in breathing, cyanosis and the large infantile hemangiomas on the mandibular segment. Her eyes were closed and she was unresponsive to painful stimulus. She had all signs of heart failure and massive hepatomegaly. The patient expired due to cardiac failure, despite rapid digitalization. Although the postmortem examination could not be realized to make the correct diagnosis, we thought that this patient might have had a PHACE syndrome.
Infantile hemangioma can be linked to particular congenital organ malformations. These dysmorphic features in PHACES syndrome include; Posterior fossa brain malformations, Hemangiomas of the cervicofacial region, Arterial anomalies, Coarctation of the aorta and cardiac defects, Eye abnormalities, Sternal cleft and supraumbilical raphe. Sternal defects were added later. Drolet et al. referred to the abnormalities as the PHACES syndrome [7].
Large lumbosacral hemangioma associated with congenital anomalies is LUMBAR syndrome. The LUMBAR syndrome includes: Lower body hemangioma often extending onto a unilateral lower extremity, Urogenital anomalies, Ulceration, Myelopathy, Bony deformities, Anorectal malformations, Arterial anomalies and Renal anomalies [7, 32, 35].
The PHACE syndrome is observed in 2–3% of IHs and in these patients cerebrovascular abnormalities 83–91% and cardiac abnormalities 41–67% are the most common manifestations. Higher risk of ocular and central nervous system involvement can be seen when IHs are on the frontotemporal and frontonasal segments, whereas a greater risk of midline and cardiovascular defects is higher when IHs develop on the mandibular segment. Additionally endocrine abnormalities, such as thyroid dysfunction, hypopituitarism with growth hormone deficiency, adrenal insufficiency and neonatal hypoglycemia, have been described [36]. The presence of a large facial segmental often superficial IH is the major sign of PHACE syndrome. In the literature, over 300 patients were reported and it is considered one of the most common neurocutaneous vascular disorders in childhood [36].
6.1 Complications of infantile hemangiomas
Important complications may occur in the patients with IHs according to the size, the anatomic localization, the superficiality and the depth of tumors. High-risk groups of IHs identified by The American Academy of Pediatrics (AAP) published its first clinical practice guideline (CPG) for the management of IHs in 2018.
Segmental lesions are often associated with complications. Pediatricians should identify the high-risk IH group before 3 months of age, ideally at 1 month of age [3]. Risk stratification in these patients is principal for diagnosis and early treatment. Ulceration, infection and bleeding are the most common complications in superficial IHs [32, 37]. Chamlin et al. reported that ulceration occurred in 15.8% of 1096 total patients with IHs and located on the lower lip, neck or anogenital region. Ulceration occurred at a median age of 4 months and bleeding developed in 41%. IHs with ulcerations were large, mixed clinical type and segmental morphologic type [37, 38]. In addition, skin ulceration is causing pain, scarring and unesthetic sequelae [37, 38]. Recurrence occurred in 16% of the treated cases [38]. Infantile hemangiomas with life-threatening complications include obstructive airway hemangiomas and hepatic hemangiomas, heart failure and hypothyroidism. These complications may develop when the IHs localize in the beard area and the patient has multiple >5 cutaneous lesions, respectively [32].
Functional impairment, such as visual disturbances, astigmatism, anisometropia, retrobulbar involvement (Figures 9 and 10), tear duct obstruction, proptosis, amblyopia, may occur in periocular IHs, especially in patients of upper eyelid IHs larger than 1 cm.
Figure 9.
T2-weighted axial magnetic resonance imaging (MRI) showing retro-orbital infantile hemangioma in a 2-month-old girl.
Figure 10.
Significant decrease of the tumor after 11 months of therapy with prednisone + IFN-α-2a.
On the other hand, feeding problems may occur in cases with nasal or lip, oral cavity IHs [3]. Disfigurement develops in IHs localized on noise, ears and perioral area, or large facial area. Segmental and facial IHs show a high risk of unesthetic sequelae, complications and recurrence [38].
Glucocorticosteroids, interferon-alpha-2a and interferon-alpha-2b therapy for high-risk hemangiomas were effective, well-tolerated treatments before 2008 [39, 40, 41]. Léaute-Labrèze et al. discovered the beneficial effects of propranolol for severe IHs and since 2008, propranolol has become the first line of treatment [42].
6.2 Diagnosis and differential diagnosis
The diagnosis is mainly based on clinical appearance. Several factors provide clues for accurate diagnosis, such as the timing of appearance of the lesion, changes in size, color over time and tactile qualities [43]. Dermoscopy, which is useful for evaluating the precise vascular structure, typically shows a polymorphous vascular structure with or without obvious red linear vessels and red dilated vessels in IHs [44, 45]. Biopsy and pathological diagnosis are rarely required when IH is differentiated from congenital hemangiomas (CHs) and vascular abnormalities. Ultrasonography is generally the preferred modality, especially in infants younger than 4 months of age. Doppler ultrasonography and MRI may be helpful in differential diagnosis [46]. Imaging may also be useful in evaluating the extent of complicated hemangioma, evaluating for other potential anomalies such as PHACES syndrome and LUMBAR syndrome or following response to therapy, particularly in the case of hepatic hemangiomas. MRI is the most sensitive technique used for definitive diagnosis of LUMBAR syndrome. In infants with >5 cutaneous lesions, abdominal ultrasonography is recommended [32]. Computed tomography (CT) should be avoided because of the increased susceptibility of children to ionizing radiation [47].
Infantile hemangiomas must be differentiated from other vascular tumors, particularly CHs and vascular malformations. Congenital hemangiomas are fully formed at birth and differ from IHs in their histological and immunohistochemical findings. GLUT-1 immunoreactivity is a diagnostically useful marker that is positive in all the development phases of IHs and negative in CHs and other vascular tumors [18, 25].
Rapidly Involuting Congenital Hemangiomas (RICH) and Non-Involuting Congenital Hemangiomas (NICH) that form in utero have no sex predilection, are pink or violet in color and do not grow postnatally (Figure 11).
Figure 11.
A 2-month-old boy has congenital hemangioma on the preauricular area.
Lesions are usually noted around the elbows and knees and along the mandibular border [44, 47]. Ayturk et al. discovered GNAQ and GNA11 gene mutations in CHs [48], predicting that CHs may represent a distinct clinical entity, caused by point mutations in GNAQ and GNA11. It has been suggested that these mutations and alterations affecting related molecular pathways could be a target for future treatment [48, 49].
Melgosa Ramos et al. retrospectively analyzed and compared 34 patients with CHs and 70 patients with IHs. They found that head and neck locations were 42.8% for IHs and the lower limbs/perineum location 32.3% for CHs. Both tumors were more common in girls. The studied risk factors were more common in patients with IHs. The most frequent component in both CHs and IHs was superficial lesions, while deep lesions were more common in CHs (14 vs. 4%). Treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment in this analysis [50]. Other differential diagnoses include tufted angioma, spindle-cell hemangioma, epithelioid hemangioma, pyogenic granuloma, locally aggressive or borderline and malignant vascular tumors.
The International Society for the Study of Vascular Anomalies (ISSVA) classification differentiates lesions with proliferative endothelium from lesions with structural anomalies. Capillary malformations (CMs), which are well-circumscribed pink to purple macular lesions of variable size, typically develop on the head and neck. They are usually unilateral. CMs may develop as an element of Sturge-Weber syndrome (Figure 12) and Klippel-Trenaunay-Weber syndrome (Figure 13) [3, 51].
Figure 12.
The picture of a 20-day-old boy with Sturge-Weber syndrome showing port-wine stain on the right upper face and eyelid.
Figure 13.
Klippel-Trenaunay-Weber syndrome consists of port-wine stains of the trunk and the right lower extremities with hemihypertrophy.
6.3 Prognosis
In most cases, the IHs resolve spontaneously during the first few years of life, approximately 30% of IHs have involved by age 4, 50% by age 5 and 75% by age 7. During the involution process, a change in the color from bright red to opaque pinkish-gray areas is observed in the center of the surface. The affected area may be normal, but more commonly it shows subtle atrophy and telangiectasia, particularly in the lips and eyelids. Areas of previous ulceration frequently leave yellowish scars [29]. Early resolutions are probably not affected by the size of the lesions, by their site or by the number of lesions present. An early onset of resolution is generally associated with a more rapid disappearance and a superior cosmetic result [7].
Infants with multiple (>5) lesions are at risk of extracutaneous involvement, particularly hepatic hemangioma is associated with poor prognosis. A small hemangioma can obstruct the airway or visual pathway with functional impairment and sometimes they can even threaten the patient’s life [3]. The vascular and structural anomalies in the brain are the most frequent extracutaneous involvement in the cases with PHACE syndrome. The deficiency of neurological and cognitive functions can be the probable reason for morbidity [36]. Early referral to a specialist, especially patients with high-risk groups, is most important.
Infantile hemangioma is the most common benign tumor of infancy, developing in 10 to 12% of infants by the first year of life. Early diagnosis at 1 week to 1 month of age and timely referral of patients with high-risk IHs to a specialist are important in preventing associated morbidity. Segmental IHs may be related to extracutaneous manifestations. Infantile hemagiomas can be rarely associated with multiple congenital structural anomalies, such as PHACE and LUMBAR syndromes. The pediatrician should carefully observe the patient with notable features and should perform the necessary examinations for correct diagnosis and early treatment.
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Written By
Sevgi Gözdaşoğlu
Submitted: 05 March 2024Reviewed: 18 March 2024Published: 19 June 2024
Open access peer-reviewed chapter - ONLINE FIRST
