This article reviews the most current practice guidelines in the diagnosis and treatment of infantile hemangiomas. Several systemic conditions that can be associated with hemangiomas, such as PHACES syndrome, are also discussed. Propranolol has become an effective first-line treatment, and protocols for its use as well as its potential risks are outlined.
- •
Correct diagnosis of hemangioma is imperative for appropriate treatment.
- •
Be familiar with the current classification of all vascular anomalies.
- •
Infantile hemangiomas are benign with a defined clinical course, involution only occurring in infancy and never later.
- •
Large, obstructing, or ulcerative lesions require early treatment to prevent functional deficits, pain, and physical deformity.
- •
Physicians should be aware of syndromes/conditions that can be associated with hemangiomas.
- •
Propranolol has revolutionized how hemangiomas are treated, but caution should be exercised.
Hemangiomas can present as focal or segmental lesions and superficial, deep, or compound in nature. Although most hemangiomas are solitary lesions in uncomplicated locations, a significant number will present in locations with higher morbidity or as a component of a more systemic disease process. This review is intended to assist the practitioner with the diagnostic tools and therapeutic options that are essential in the proper management of these common yet sometimes challenging lesions.
Demographics of hemangiomas
Hemangiomas are found in 4% to 10% of all infants and in up to 30% of premature babies. Sixty percent of hemangiomas are found in the head and neck region. The most common predisposing factors for the development of a hemangioma are :
- •
Caucasian ethnicity
- •
Female sex (71% female or 2.4:1 female-to-male ratio)
- •
Low birth weight
- •
Products of multiple gestations.
Advanced maternal age and the presence of placenta previa have also been shown to be significant factors.
Many retrospective and prospective studies have focused on elucidating the reason for this specific demographic distribution, with very few answers.
Etiology of hemangiomas
The inheritance of hemangiomas is mainly sporadic. However, in a study by Haggstrom and colleagues, one-third of their patients with hemangiomas had a first-degree relative with a vascular lesion and 12% had a first-degree relative who had a hemangioma. Genetic research has discovered an association with chromosome 5, but this has only been discovered in a small percentage of patients. Autosomal dominance has also been reported in some cases.
Although the genetic factors are often uncertain, the basic nature of hemangiomas is becoming increasingly well understood. An active area of current hemangioma research is the molecular markers and growth factors associated with hemangiomas. In a landmark article, North and colleagues described the presence of GLUT1, a glucose transporter typically limited to endothelium in tissues with a blood-tissue barrier, which was present in 97% of the juvenile hemangiomas studied. The investigators then discovered that GLUT1 was not present in any other vascular lesions including pyogenic granulomas, granulation tissue, and venous, lymphatic, or arteriovenous malformations. Further studies identified other markers such as FcγRII, merosin, and LeY, which are all present in hemangiomas as well as placental tissue while being spared in other body tissues. The tissue architecture of hemangiomas is, however, different to that of placental tissue, which suggests a common progenitor cell or a shared regulatory mechanism.
A few hypotheses have been presented to explain the “hemangioma-placental connection.” These theories include somatic mutations, abnormal local inductive influences from the placenta, or placental emboli that were shed and received by the developing placental tissues. Of these, the embolic theory has found some support, as patients with chorionic villus sampling have been found to have an increased incidence of hemangiomas.
Etiology of hemangiomas
The inheritance of hemangiomas is mainly sporadic. However, in a study by Haggstrom and colleagues, one-third of their patients with hemangiomas had a first-degree relative with a vascular lesion and 12% had a first-degree relative who had a hemangioma. Genetic research has discovered an association with chromosome 5, but this has only been discovered in a small percentage of patients. Autosomal dominance has also been reported in some cases.
Although the genetic factors are often uncertain, the basic nature of hemangiomas is becoming increasingly well understood. An active area of current hemangioma research is the molecular markers and growth factors associated with hemangiomas. In a landmark article, North and colleagues described the presence of GLUT1, a glucose transporter typically limited to endothelium in tissues with a blood-tissue barrier, which was present in 97% of the juvenile hemangiomas studied. The investigators then discovered that GLUT1 was not present in any other vascular lesions including pyogenic granulomas, granulation tissue, and venous, lymphatic, or arteriovenous malformations. Further studies identified other markers such as FcγRII, merosin, and LeY, which are all present in hemangiomas as well as placental tissue while being spared in other body tissues. The tissue architecture of hemangiomas is, however, different to that of placental tissue, which suggests a common progenitor cell or a shared regulatory mechanism.
A few hypotheses have been presented to explain the “hemangioma-placental connection.” These theories include somatic mutations, abnormal local inductive influences from the placenta, or placental emboli that were shed and received by the developing placental tissues. Of these, the embolic theory has found some support, as patients with chorionic villus sampling have been found to have an increased incidence of hemangiomas.
Classification of hemangiomas among vascular anomalies
The distinction of hemangiomas from other vascular lesions is a critical area of understanding for any practitioner who may see these patients. Although hemangiomas are the most common vascular lesion, not all vascular lesions are hemangiomas, and each type of lesion will have its own specific clinical course.
In 1982, Mulliken and Glowacki published a classification scheme that has been used as the primer for the current internationally accepted nomenclature and distinction of vascular lesions. This classification separated vascular anomalies into 2 major categories: (1) vascular tumors and (2) vascular malformations.
Vascular tumors grow through endothelial proliferation and have the potential for spontaneous regression. Vascular malformations, however, grow via vessel ectasia and will not resolve with time. A thorough description of each subclassification of vascular anomalies and their individual clinical course is beyond the scope of this article, and it is strongly recommended that the reader refer to the original document for further enlightenment.
Among the vascular tumors group, the dominant member is hemangiomas. Within the hemangioma category of vascular lesions, there are also different subtypes.
Infantile Hemangiomas
Hemangiomas that are not identified at birth or are very small and then progressively grow are called infantile hemangiomas. These hemangiomas follow a proliferative growth phase followed by quiescence and involution, and are the focus of this review.
Infantile hemangiomas can be:
- •
Focal or segmental
- •
Superficial or deep
- •
Single or diffuse.
These factors can help the practitioner with risk stratification and may provide a clue to a more systemic process.
Congenital Hemangiomas
Those hemangiomas that are fully developed at birth and do not undergo more than proportional postnatal growth are called congenital hemangiomas. These lesions are rare and have an incidence of about 3% of all hemangiomas. Histologically they are different from infantile hemangiomas. Within the congenital hemangioma category, there are also 2 subtypes :
- 1.
Noninvoluting congenital hemangioma (NICH).
- 2.
Rapidly involuting congenital hemangioma (RICH).
Clinical course of hemangiomas
Infantile hemangiomas are vascular tumors that grow intermittently throughout the first year of life. The majority achieve up to two-thirds of their size during the first 5 months of life. Some infantile hemangiomas are visibly present at birth and others are noticed later, depending on depth and extent. Close observation and early subspecialist referral should be considered during this early growth phase.
The growth of infantile hemangiomas proceeds through different phases: the proliferative phase continues usually throughout the first 9 to 12 months of life followed by quiescence, which is of variable length, and then involution, which may last several years.
Proliferative Phase
During the proliferative phase of an infantile hemangioma, it is important for the practitioner to monitor the patient closely. It is typically during this phase that early treatment is considered if significant growth is occurring, ulceration results, or functional consequences are developing. Ulceration is common in rapidly growing lesions that have a superficial component. Such lesions can cause significant pain, bleeding, and excessive scarring if they are not recognized and treated early.
Quiescence/Involution
Once the rapid growth phase tapers off the involuting phase commences, which includes the stabilization of the size of the tumor and commencement of regression. Practically all infantile hemangiomas eventually involute, but the timing of involution and extent of hemangioma regression can be highly variable. The earliest signs of involution commonly include a graying of the lesion centrally and often a subtle, diffuse darkening of the lesion. This phase is typically the longest, with completion of involution taking from 1 to 7 years. Once a hemangioma has entered the involution phase it never regrows, which helps distinguish hemangiomas from vascular malformations.
Involuted Phase
The final presentation of the infantile hemangioma is the involuted phase. The involuted hemangioma is typically found to have overlying atrophic skin and excessive fibrofatty tissue with overlying telangiectasias.
Special considerations in hemangiomas
Beard-Distribution Hemangiomas
Beard-distribution hemangiomas involve the V3 distribution of the trigeminal nerve. These patients have segmental superficial hemangiomas along preauricular and mandibular distribution including the lower lip, as well as airway involvement. These patients also frequently have hemangioma involvement of both parotid glands. Most importantly, patients with beard-distribution hemangiomas commonly have airway involvement, typically in the subglottis. Airway hemangiomas occur in about 65% of beard-distribution hemangiomas and are frequently not symptomatic until the fourth to eighth week of life when hemangioma growth is most rapid. It is recommended that all patients, when diagnosed with a beard-distribution hemangioma, undergo diagnostic microlaryngoscopy and bronchoscopy to ascertain the presence of airway involvement. It should also be noted that hemangioma can occur anywhere in the airway, but subglottic involvement is usually the most problematic ( Fig. 1 ).
PHACES Syndrome
Segmental superficial hemangiomas in the head and neck should alert the physician to the possibility of PHACES syndrome; this is especially true if the hemangioma is in the V1, V2, or scalp distribution. PHACES syndrome can represent abnormalities in :
Posterior cranial fossa (frequently cerebellum)
Hemangiomas of the face/scalp
Arterial abnormalities
Cardiac abnormalities
Eye abnormalities
Sternal clefting (or umbilical raphe).
Patients with segmental hemangiomas of the face/scalp need to have further diagnostic studies to rule out other abnormalities. A careful physical examination, looking for outward defects such as ocular hemangioma/strabismus as well as sternal or umbilical raphe, should be performed. Diagnostic studies that should be obtained include:
- •
Magnetic resonance imaging (MRI)/magnetic resonance angiography of the brain/face/neck to look for intracranial and arterial abnormalities
- •
Echocardiogram to examine the cardiac structures
- •
Ophthalmologic examination ( Fig. 2 ).
