A Teen’s Large Congenital Hemangioma: Successful Treatment With Propranolol
A 17-year-old adolescent presented with a chief concern of right foot pain. She had a large congenital internal hemangioma extending from the tips of her right toes up toward her right upper thigh. She had been monitored about a decade ago by a vascular team, and therapy had not been tried at that time.
On physical examination, an erythematous, reticulated and confluent macular rash was present at the end of the first, second, and third digits of the right foot (Figure 1), extending up to the right upper thigh. An area of violaceous bulging (approximately 2 cm) on the volar surface of the right foot, just at the proximal end of the first digit, was tender to palpation (Figure 2). Mild ecchymosis was noted around the tender, bulging lesion. The rest of the physical examination findings were unremarkable.
Results of magnetic resonance imaging (MRI) showed increased vascularization on the girl’s right side, consistent with hemangioma, on her right calf, and her right foot (Figure 3).
Figure 1: An erythematous, reticulated and confluent macular rash was present at the end of the first, second, and third digits of the right foot, extending up to the right upper thigh.
The girl was started on a daily regimen of 40 mg of oral propranolol, which led to significant improvement in the pain and appearance of the hemangioma. She experienced headaches after 1 week of propranolol use, at which point the daily dose was decreased to 20 mg; her hemangioma still responded well. She reported no longer having throbbing pain on the volar side of her foot, and she and her mother were very pleased that the hemangioma had lightened in color and that her foot “looked less swollen” (Figure 4).
Propranolol therapy was discontinued after 3 months, and the hemangioma had not increased in size at a follow-up visit 7 months later.
Figure 2: An approximately 2 cm area of violaceous bulging was present on the volar surface of the adolescent’s right foot, just at the proximal end of the first toe. Mild ecchymosis was visible around the lesion, which was tender to palpation.
While no single theory explains all characteristics of hemangiomas, it is widely accepted that they are endothelial tumors whose biological architecture differs from vascular malformations. Hemangiomas usually occur after birth and spontaneously resolve.1
A hemangioma usually is a benign swelling or growth of endothelial cells that line blood vessels, allowing these vessels to increase in number and also allowing them to increase their capacity to hold larger volumes of blood. Some studies have suggested that estrogen signals proliferation of hemangiomas. Glucose transporter type 1 (GLUT-1) is a histochemical marker specific for hemangioma and used to differentiate from vascular formations.2
Figure 3: Magnetic resonance imaging scans showed increased vascularization on the right calf, lower leg, and foot, consistent with hemangioma.
Hemangiomas can be diagnosed clinically. Skin biopsies can be performed and will positively stain for GLUT-1 during the proliferation process. MRI and ultrasonography aid in assessing the extent of cutaneous and extracutaneous hemangiomas.
The list of differential diagnoses includes capillary malformations (eg, port-wine stain, or nevus flammeus), Cobb syndrome, Klippel-Trénaunay syndrome, Proteus syndrome, and Rubinstein-Taybi syndrome.
Figure 4: A daily regimen of 40 mg of oral propranolol, which later was reduced to 20 mg because of headache, led to significant improvement in the girl’s hemangioma.
Intervention frequently is indicated for infantile hemangiomas, because there is no way to predict the size that proliferative infantile hemangiomas will reach, and it is hard to predict complications.
Oral propranolol at a dose of 2 to 3 mg/kg/day is recommended if the hemangioma interferes with daily function, as it did in our patient’s case. Propranolol is a nonselective β-adrenergic receptor antagonist with a consistent, rapid therapeutic effect and excellent tolerability.3 For superficial hemangiomas, topical propranolol ointment can be applied. One study showed regression of hemangiomas in 59% of 45 children and a completely stoppage of growth in 26% of them, with no clinical adverse effects noted.4 In the study, the children’s hemangiomas were demonstrated not to be deep via ultrasonography, and a hydrophilic ointment of propranolol, 1%, was applied daily.
The mechanisms of propranolol therapy include constriction of vessels, reduction of vascular endothelial growth factors, and initiation of apoptosis. The evolution of propranolol’s use as a therapy for hemangioma began with 2 children who were being treated with propranolol for heart failure. The medication had remarkable results. The children’s hemangiomas softening and shrinking and the color lightening. Clinical trials began in children who had disfiguring hemangiomas; positive results led to larger studies, and all trials demonstrated improvement.5 Relapses generally are mild and respond to retreatment.
Treatment options also include a conservative approach with regular monitoring and attention to psychological implications for the child and family; systemic corticosteroids; and, for aggressive hemangiomas unresponsive to corticosteroids, vincristine (a mitosis inhibitor) and interferon-alfa (which can be neurotoxic). Other treatment options include lasers and surgical excision.
Jennifer Zamora, MPAP, PA-C, is a physician assistant at Pediatric Medical Group in Riverside, California, and an adjunct professor of pediatrics at the University of Southern California in Los Angeles, California.
Alan Kwasman, MD, is a pediatrician at Pediatric Medical Group and an adjunct professor of pediatrics at the University of California Riverside School of Medicine in Riverside, California.
Timothy Mackey, MD, is a pediatrician at Pediatric Medical Group and an adjunct professor of pediatrics at the University of California Riverside School of Medicine in Riverside, California.
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