H emangiomas of infancy are common lesions in the pediatric population. Most undergo a predictable natural history with spontaneous resolution over years. For these patients, reassurance and education is all that is needed. However, a small subset of patients will have problems that include local and systemic complications. For the clinician, it’s essential that these patients are not overlooked and that further investigations and intervention occur in a timely manner. Background Hemangiomas of infancy are seen in up to 12% of infants 1 year of age or younger, making them the most common tumor of infancy.1,2 They are clinically and pathologically distinct from vascular malformations, such as port-wine stains. For the purpose of this article, we will refer to them as hemangiomas of infancy (HOI) to distinguish them from other vascular tumors, such as congenital hemangiomas and Kaposiform hemangioendotheliomas. Known risk factors for the development of HOI include female sex,3 premature delivery4,5 and exposure to chorionic villi sampling in utero.6 Recently, autosomal dominant transmission has been reported in six kindreds.7 Natural History The natural history for HOI has been well documented. A raised vascular tumor is absent at birth, although precursor lesions, such as a telangiectatic or erythematous macule/patch, can be seen in up to 50% of patients.3,8 The rapid growth phase of HOI is most pronounced in the first 3 to 6 months, followed by slower growth afterward. Most reach their maximum size by 12 months of age. There can be wide variability in the timing of growth and stabilization between different patients. Complete involution of HOI occurs at a rate of approximately 10% per year, with 50% of patients having resolution by 5 years of age and 90% by 9 years of age. In some hemangiomas, fibro-fatty infiltration may occur when the lesions resolve. Ulceration is the most frequent complication of hemangiomas, occurring in 5% to 13% of all lesions.9 This usually takes place in the proliferative phase and is more common in areas of mechanical trauma such as the perineum, the perioral area and intertriginous areas. Hemangiomas that are segmental are more likely to ulcerate. Problematic Hemangiomas Although most hemangiomas require active non-intervention, some locations are associated with potential functional complications and/or herald systemic involvement. 1. Periorbital Hemangiomas Hemangiomas that develop around the eye warrant particular attention, as they can cause amblyopia. This may be due to either unequal refraction secondary to mechanical distortion of the globe or visual deprivation secondary to obstruction of the visual axis. Amblyopia occurs in up to 60% of children with periorbital hemangiomas.10,11 Although treatment will depend on the degree of visual compromise, most of these infants require treatment with systemic corticosteroids. Referral to an ophthalmologist familiar with the management of periorbital hemangiomas is essential as the loss of visual input at a crucial time in neuro-ophthalmological development may lead to permanent visual loss. 2. Airway Hemangiomas Airway hemangiomas are rare, but potentially life-threatening. They may occur in isolation or be associated with cutaneous lesions. Symptomatic hemangiomas of the upper airway or subglottic areas are highly associated with cutaneous cervico-facial hemangiomas in a “beard” distribution (including the preauricular areas, chin, anterior neck, and lower lip). A recent study revealed that 63% of patients with cutaneous lesions in a beard distribution had some degree of symptomatic airway involvement, with 40% of these patients requiring tracheostomy.12 In these patients, symptoms often occur within the first 6 to 12 weeks of age. An otolaryngology referral is recommended for all infants with HOI in the beard distribution. If airway hemangiomas are noted, systemic treatment should be considered. Parents and physicians should closely observe these patients for symptomatic airway disease, such as inspiratory and/or expiratory stridor. Prompt laryngoscopy is necessary, if these symptoms develop. 3. Lumbosacral Hemangiomas The presence of a midline HOI in the lumbrosacral area suggests an underlying spinal dysraphism and/or urogenital anomaly.13 These children often have no other initial signs aside from the hemangioma, highlighting the importance of recognizing this association. Other extracutaneous findings include anorectal anomalies like imperforate anus, rectal fistulae, renal anomalies, abnormal genitalia and other spinal cord abnormalities.14,15 As such, imaging is warranted for any HOI overlying the lumbosacral area, including those that extend from the anus into the gluteal cleft. A MRI is the best modality to look at spinal dysraphism, but an ultrasound of the spine may be sufficient for patients less than 6 months of age. 4. Hepatic Hemangiomas Another area of concern involves hemangiomas of the liver. In diffuse hemangiomatosis (see below), multiple cutaneous hemangiomas may be a clue to underlying liver involvement. Hepatic hemangiomas may also occur in isolation. At times, they are asymptomatic and found incidentally by ultrasonography. Complications related to the presence of liver hemangiomas include hepatomegaly, congestive heart failure, obstructive jaundice, anemia and thrombocytopenia.16,17 In particular, tumors that have arterio-venous shunts and/or porto-venous shunts are highly associated with congestive heart failure.17 There have also been recent reports of thyroid abnormalities associated with large or multiple hemangiomas.18-20 Treatment of hepatic hemangiomas may necessitate treatment of congestive heart failure and measures to decrease flow through the hemangioma by medical or surgical means. Medical management includes systemic corticosteroids, vincristine (Oncovin) or cyclophosphamide (Cytoxan). Surgical therapy includes embolization, hepatic artery ligation, hepatic resection and even liver transplantation. Hypothyroidism associated with hepatic hemangiomas should be recognized early and treated aggressively to restore euthyroid status early. Some may necessitate large quantities of L-thyroxine, due to consumptive hypothyroidism.18-20 5. PHACES Syndrome The association between facial hemangiomas and other anomalies such as posterior fossa malformations, arterial anomalies, coarctation of the aorta, cardiac defects, eye abnormalities and sternal defects has been well described in the literature, and the term “PHACES” syndrome was coined by Frieden and Cohen in 1996.21 (See Table 1 above.) Nearly all of these infants will have large facial hemangiomas that are plaque-like and segmental. Approximately 90% of patients with PHACES syndrome are female, a higher ratio than the 3-5:1 female to male ratio of HOI.21,22 Not all will have the full clinical spectrum of the syndrome and up to 70% of patients have only one extracutaneous manifestation.22 Although the syndrome is rare, its presence is significant due to potential for progressive neurovascular disease. As such, PHACES syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac and neurologic assessment. The work-up should include echocardiography and brain imaging (MRI). 6. Hemangiomatosis Most HOIs are solitary, though up to 20% of them are multiple.23 In neonatal hemangiomatosis, patients have many small, generalized hemangiomas that often have visceral involvement. The patient may follow a benign course or have diffuse neonatal hemangiomatosis. The benign form presents at birth with multiple cutaneous hemangiomas that spontaneously resolve without symptomatic visceral involvement.24 In contrast, the diffuse form is a serious multisystem syndrome of multiple cutaneous hemangiomas, visceral hemangiomatosis with arterio-venous shunts, high output congestive heart failure, obstructive hydrocephalus, thrombocytopenia with hemorrhage and central nervous system involvement.24,25 Some authors recommend a screening ultrasound for any infant who presents with five or more cutaneous hemangiomas.3 Other tests that can be considered include a complete blood count, liver enzymes, coagulation studies, a chest radiograph, electrocardiogram, brain imaging (MRI) and an ophthalmology consult.23 Considerations to Remember Hemangiomas of infancy are common lesions in infancy and usually follow a predictable natural history with a benign outcome. Parents should be reassured of eventual regression of the HOI with little or no residual effects. However, the clinician should be aware of hemangiomas that are more likely to ulcerate, those that are near mucosal membranes and hemangiomas that are in a segmental pattern. Particular attention should be given to hemangiomas that are in certain anatomic areas. These hemangiomas include periorbital, lumbo-sacral and ‘beard’ distribution hemangiomas. In addition, consider systemic involvement in liver hemangiomas, segmental plaque-type facial hemangiomas and multiple cutaneous hemangiomas. (See Table 2.) Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
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Hemangiomas of Infancy: When Treatment Is Essential
H emangiomas of infancy are common lesions in the pediatric population. Most undergo a predictable natural history with spontaneous resolution over years. For these patients, reassurance and education is all that is needed. However, a small subset of patients will have problems that include local and systemic complications. For the clinician, it’s essential that these patients are not overlooked and that further investigations and intervention occur in a timely manner. Background Hemangiomas of infancy are seen in up to 12% of infants 1 year of age or younger, making them the most common tumor of infancy.1,2 They are clinically and pathologically distinct from vascular malformations, such as port-wine stains. For the purpose of this article, we will refer to them as hemangiomas of infancy (HOI) to distinguish them from other vascular tumors, such as congenital hemangiomas and Kaposiform hemangioendotheliomas. Known risk factors for the development of HOI include female sex,3 premature delivery4,5 and exposure to chorionic villi sampling in utero.6 Recently, autosomal dominant transmission has been reported in six kindreds.7 Natural History The natural history for HOI has been well documented. A raised vascular tumor is absent at birth, although precursor lesions, such as a telangiectatic or erythematous macule/patch, can be seen in up to 50% of patients.3,8 The rapid growth phase of HOI is most pronounced in the first 3 to 6 months, followed by slower growth afterward. Most reach their maximum size by 12 months of age. There can be wide variability in the timing of growth and stabilization between different patients. Complete involution of HOI occurs at a rate of approximately 10% per year, with 50% of patients having resolution by 5 years of age and 90% by 9 years of age. In some hemangiomas, fibro-fatty infiltration may occur when the lesions resolve. Ulceration is the most frequent complication of hemangiomas, occurring in 5% to 13% of all lesions.9 This usually takes place in the proliferative phase and is more common in areas of mechanical trauma such as the perineum, the perioral area and intertriginous areas. Hemangiomas that are segmental are more likely to ulcerate. Problematic Hemangiomas Although most hemangiomas require active non-intervention, some locations are associated with potential functional complications and/or herald systemic involvement. 1. Periorbital Hemangiomas Hemangiomas that develop around the eye warrant particular attention, as they can cause amblyopia. This may be due to either unequal refraction secondary to mechanical distortion of the globe or visual deprivation secondary to obstruction of the visual axis. Amblyopia occurs in up to 60% of children with periorbital hemangiomas.10,11 Although treatment will depend on the degree of visual compromise, most of these infants require treatment with systemic corticosteroids. Referral to an ophthalmologist familiar with the management of periorbital hemangiomas is essential as the loss of visual input at a crucial time in neuro-ophthalmological development may lead to permanent visual loss. 2. Airway Hemangiomas Airway hemangiomas are rare, but potentially life-threatening. They may occur in isolation or be associated with cutaneous lesions. Symptomatic hemangiomas of the upper airway or subglottic areas are highly associated with cutaneous cervico-facial hemangiomas in a “beard” distribution (including the preauricular areas, chin, anterior neck, and lower lip). A recent study revealed that 63% of patients with cutaneous lesions in a beard distribution had some degree of symptomatic airway involvement, with 40% of these patients requiring tracheostomy.12 In these patients, symptoms often occur within the first 6 to 12 weeks of age. An otolaryngology referral is recommended for all infants with HOI in the beard distribution. If airway hemangiomas are noted, systemic treatment should be considered. Parents and physicians should closely observe these patients for symptomatic airway disease, such as inspiratory and/or expiratory stridor. Prompt laryngoscopy is necessary, if these symptoms develop. 3. Lumbosacral Hemangiomas The presence of a midline HOI in the lumbrosacral area suggests an underlying spinal dysraphism and/or urogenital anomaly.13 These children often have no other initial signs aside from the hemangioma, highlighting the importance of recognizing this association. Other extracutaneous findings include anorectal anomalies like imperforate anus, rectal fistulae, renal anomalies, abnormal genitalia and other spinal cord abnormalities.14,15 As such, imaging is warranted for any HOI overlying the lumbosacral area, including those that extend from the anus into the gluteal cleft. A MRI is the best modality to look at spinal dysraphism, but an ultrasound of the spine may be sufficient for patients less than 6 months of age. 4. Hepatic Hemangiomas Another area of concern involves hemangiomas of the liver. In diffuse hemangiomatosis (see below), multiple cutaneous hemangiomas may be a clue to underlying liver involvement. Hepatic hemangiomas may also occur in isolation. At times, they are asymptomatic and found incidentally by ultrasonography. Complications related to the presence of liver hemangiomas include hepatomegaly, congestive heart failure, obstructive jaundice, anemia and thrombocytopenia.16,17 In particular, tumors that have arterio-venous shunts and/or porto-venous shunts are highly associated with congestive heart failure.17 There have also been recent reports of thyroid abnormalities associated with large or multiple hemangiomas.18-20 Treatment of hepatic hemangiomas may necessitate treatment of congestive heart failure and measures to decrease flow through the hemangioma by medical or surgical means. Medical management includes systemic corticosteroids, vincristine (Oncovin) or cyclophosphamide (Cytoxan). Surgical therapy includes embolization, hepatic artery ligation, hepatic resection and even liver transplantation. Hypothyroidism associated with hepatic hemangiomas should be recognized early and treated aggressively to restore euthyroid status early. Some may necessitate large quantities of L-thyroxine, due to consumptive hypothyroidism.18-20 5. PHACES Syndrome The association between facial hemangiomas and other anomalies such as posterior fossa malformations, arterial anomalies, coarctation of the aorta, cardiac defects, eye abnormalities and sternal defects has been well described in the literature, and the term “PHACES” syndrome was coined by Frieden and Cohen in 1996.21 (See Table 1 above.) Nearly all of these infants will have large facial hemangiomas that are plaque-like and segmental. Approximately 90% of patients with PHACES syndrome are female, a higher ratio than the 3-5:1 female to male ratio of HOI.21,22 Not all will have the full clinical spectrum of the syndrome and up to 70% of patients have only one extracutaneous manifestation.22 Although the syndrome is rare, its presence is significant due to potential for progressive neurovascular disease. As such, PHACES syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac and neurologic assessment. The work-up should include echocardiography and brain imaging (MRI). 6. Hemangiomatosis Most HOIs are solitary, though up to 20% of them are multiple.23 In neonatal hemangiomatosis, patients have many small, generalized hemangiomas that often have visceral involvement. The patient may follow a benign course or have diffuse neonatal hemangiomatosis. The benign form presents at birth with multiple cutaneous hemangiomas that spontaneously resolve without symptomatic visceral involvement.24 In contrast, the diffuse form is a serious multisystem syndrome of multiple cutaneous hemangiomas, visceral hemangiomatosis with arterio-venous shunts, high output congestive heart failure, obstructive hydrocephalus, thrombocytopenia with hemorrhage and central nervous system involvement.24,25 Some authors recommend a screening ultrasound for any infant who presents with five or more cutaneous hemangiomas.3 Other tests that can be considered include a complete blood count, liver enzymes, coagulation studies, a chest radiograph, electrocardiogram, brain imaging (MRI) and an ophthalmology consult.23 Considerations to Remember Hemangiomas of infancy are common lesions in infancy and usually follow a predictable natural history with a benign outcome. Parents should be reassured of eventual regression of the HOI with little or no residual effects. However, the clinician should be aware of hemangiomas that are more likely to ulcerate, those that are near mucosal membranes and hemangiomas that are in a segmental pattern. Particular attention should be given to hemangiomas that are in certain anatomic areas. These hemangiomas include periorbital, lumbo-sacral and ‘beard’ distribution hemangiomas. In addition, consider systemic involvement in liver hemangiomas, segmental plaque-type facial hemangiomas and multiple cutaneous hemangiomas. (See Table 2.) Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
H emangiomas of infancy are common lesions in the pediatric population. Most undergo a predictable natural history with spontaneous resolution over years. For these patients, reassurance and education is all that is needed. However, a small subset of patients will have problems that include local and systemic complications. For the clinician, it’s essential that these patients are not overlooked and that further investigations and intervention occur in a timely manner. Background Hemangiomas of infancy are seen in up to 12% of infants 1 year of age or younger, making them the most common tumor of infancy.1,2 They are clinically and pathologically distinct from vascular malformations, such as port-wine stains. For the purpose of this article, we will refer to them as hemangiomas of infancy (HOI) to distinguish them from other vascular tumors, such as congenital hemangiomas and Kaposiform hemangioendotheliomas. Known risk factors for the development of HOI include female sex,3 premature delivery4,5 and exposure to chorionic villi sampling in utero.6 Recently, autosomal dominant transmission has been reported in six kindreds.7 Natural History The natural history for HOI has been well documented. A raised vascular tumor is absent at birth, although precursor lesions, such as a telangiectatic or erythematous macule/patch, can be seen in up to 50% of patients.3,8 The rapid growth phase of HOI is most pronounced in the first 3 to 6 months, followed by slower growth afterward. Most reach their maximum size by 12 months of age. There can be wide variability in the timing of growth and stabilization between different patients. Complete involution of HOI occurs at a rate of approximately 10% per year, with 50% of patients having resolution by 5 years of age and 90% by 9 years of age. In some hemangiomas, fibro-fatty infiltration may occur when the lesions resolve. Ulceration is the most frequent complication of hemangiomas, occurring in 5% to 13% of all lesions.9 This usually takes place in the proliferative phase and is more common in areas of mechanical trauma such as the perineum, the perioral area and intertriginous areas. Hemangiomas that are segmental are more likely to ulcerate. Problematic Hemangiomas Although most hemangiomas require active non-intervention, some locations are associated with potential functional complications and/or herald systemic involvement. 1. Periorbital Hemangiomas Hemangiomas that develop around the eye warrant particular attention, as they can cause amblyopia. This may be due to either unequal refraction secondary to mechanical distortion of the globe or visual deprivation secondary to obstruction of the visual axis. Amblyopia occurs in up to 60% of children with periorbital hemangiomas.10,11 Although treatment will depend on the degree of visual compromise, most of these infants require treatment with systemic corticosteroids. Referral to an ophthalmologist familiar with the management of periorbital hemangiomas is essential as the loss of visual input at a crucial time in neuro-ophthalmological development may lead to permanent visual loss. 2. Airway Hemangiomas Airway hemangiomas are rare, but potentially life-threatening. They may occur in isolation or be associated with cutaneous lesions. Symptomatic hemangiomas of the upper airway or subglottic areas are highly associated with cutaneous cervico-facial hemangiomas in a “beard” distribution (including the preauricular areas, chin, anterior neck, and lower lip). A recent study revealed that 63% of patients with cutaneous lesions in a beard distribution had some degree of symptomatic airway involvement, with 40% of these patients requiring tracheostomy.12 In these patients, symptoms often occur within the first 6 to 12 weeks of age. An otolaryngology referral is recommended for all infants with HOI in the beard distribution. If airway hemangiomas are noted, systemic treatment should be considered. Parents and physicians should closely observe these patients for symptomatic airway disease, such as inspiratory and/or expiratory stridor. Prompt laryngoscopy is necessary, if these symptoms develop. 3. Lumbosacral Hemangiomas The presence of a midline HOI in the lumbrosacral area suggests an underlying spinal dysraphism and/or urogenital anomaly.13 These children often have no other initial signs aside from the hemangioma, highlighting the importance of recognizing this association. Other extracutaneous findings include anorectal anomalies like imperforate anus, rectal fistulae, renal anomalies, abnormal genitalia and other spinal cord abnormalities.14,15 As such, imaging is warranted for any HOI overlying the lumbosacral area, including those that extend from the anus into the gluteal cleft. A MRI is the best modality to look at spinal dysraphism, but an ultrasound of the spine may be sufficient for patients less than 6 months of age. 4. Hepatic Hemangiomas Another area of concern involves hemangiomas of the liver. In diffuse hemangiomatosis (see below), multiple cutaneous hemangiomas may be a clue to underlying liver involvement. Hepatic hemangiomas may also occur in isolation. At times, they are asymptomatic and found incidentally by ultrasonography. Complications related to the presence of liver hemangiomas include hepatomegaly, congestive heart failure, obstructive jaundice, anemia and thrombocytopenia.16,17 In particular, tumors that have arterio-venous shunts and/or porto-venous shunts are highly associated with congestive heart failure.17 There have also been recent reports of thyroid abnormalities associated with large or multiple hemangiomas.18-20 Treatment of hepatic hemangiomas may necessitate treatment of congestive heart failure and measures to decrease flow through the hemangioma by medical or surgical means. Medical management includes systemic corticosteroids, vincristine (Oncovin) or cyclophosphamide (Cytoxan). Surgical therapy includes embolization, hepatic artery ligation, hepatic resection and even liver transplantation. Hypothyroidism associated with hepatic hemangiomas should be recognized early and treated aggressively to restore euthyroid status early. Some may necessitate large quantities of L-thyroxine, due to consumptive hypothyroidism.18-20 5. PHACES Syndrome The association between facial hemangiomas and other anomalies such as posterior fossa malformations, arterial anomalies, coarctation of the aorta, cardiac defects, eye abnormalities and sternal defects has been well described in the literature, and the term “PHACES” syndrome was coined by Frieden and Cohen in 1996.21 (See Table 1 above.) Nearly all of these infants will have large facial hemangiomas that are plaque-like and segmental. Approximately 90% of patients with PHACES syndrome are female, a higher ratio than the 3-5:1 female to male ratio of HOI.21,22 Not all will have the full clinical spectrum of the syndrome and up to 70% of patients have only one extracutaneous manifestation.22 Although the syndrome is rare, its presence is significant due to potential for progressive neurovascular disease. As such, PHACES syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac and neurologic assessment. The work-up should include echocardiography and brain imaging (MRI). 6. Hemangiomatosis Most HOIs are solitary, though up to 20% of them are multiple.23 In neonatal hemangiomatosis, patients have many small, generalized hemangiomas that often have visceral involvement. The patient may follow a benign course or have diffuse neonatal hemangiomatosis. The benign form presents at birth with multiple cutaneous hemangiomas that spontaneously resolve without symptomatic visceral involvement.24 In contrast, the diffuse form is a serious multisystem syndrome of multiple cutaneous hemangiomas, visceral hemangiomatosis with arterio-venous shunts, high output congestive heart failure, obstructive hydrocephalus, thrombocytopenia with hemorrhage and central nervous system involvement.24,25 Some authors recommend a screening ultrasound for any infant who presents with five or more cutaneous hemangiomas.3 Other tests that can be considered include a complete blood count, liver enzymes, coagulation studies, a chest radiograph, electrocardiogram, brain imaging (MRI) and an ophthalmology consult.23 Considerations to Remember Hemangiomas of infancy are common lesions in infancy and usually follow a predictable natural history with a benign outcome. Parents should be reassured of eventual regression of the HOI with little or no residual effects. However, the clinician should be aware of hemangiomas that are more likely to ulcerate, those that are near mucosal membranes and hemangiomas that are in a segmental pattern. Particular attention should be given to hemangiomas that are in certain anatomic areas. These hemangiomas include periorbital, lumbo-sacral and ‘beard’ distribution hemangiomas. In addition, consider systemic involvement in liver hemangiomas, segmental plaque-type facial hemangiomas and multiple cutaneous hemangiomas. (See Table 2.) Disclosure:The authors have no conflict of interest with any subject matter discussed in this month’s column.
