A 2-month-old Hispanic girl is transferred by her pediatrician to the emergency department (ED) for evaluation of decreased oral intake, failure to thrive, and large bleeding facial hemangiomas.
The infant started developing hemangiomas at 2 weeks of age, but her parents were reassured by her primary care physician that the hemangiomas would regress over time. However, they continued to grow in size and number on the baby’s face, neck, and upper back. Three weeks prior to her transfer to the ED, the hemangiomas on her upper lip and nose ulcerated. A plastic surgeon debrided the scabs on her nose, but no additional workup was done. For 2 days prior to her transfer, the baby was feeding poorly and breathing laboriously, prompting the concerned parents to seek a higher level of care for the ill child.
The patient was born full-term with normal growth and development. Her vital signs were normal, but she weighed only 3.8 kg (2.5th percentile for her age), worrisome for failure to thrive. Her hemangiomas were of various sizes, ranging from 4 mm to 10 mm, some coalescing into plaques resembling a segmental hemangioma, most prominent on the right cheek (Figure 1). She also had isolated hemangiomas on her neck, upper back, and right eyelid causing ptosis. The hemangiomas on her upper lip were ulcerated and intermittently bleeding. Her face was asymmetrical because of a subcutaneous mass in her right cheek (Figure 2). Her lungs were clear to auscultation, and she maintained good oxygen saturation. A grade 3 systolic murmur was heard on cardiac auscultation. Abdominal exam showed no tenderness or hepatosplenomegaly. She was admitted to the hospital for further evaluation.
The patient had decreased oral intake, failure to thrive, labored breathing, an asymmetrical facial mass, and a segmental facial hemangioma. The presence of a segmental hemangioma and a facial mass in conjunction with symptoms suggesting oropharyngeal obstruction raised suspicions for additional underlying vascular anomalies such as those present in neonatal hemangiomatosis, Kasabach-Merritt phenomenon, and PHACE syndrome (Table 1).1
Neonatal hemangiomatosis should be suspected in infants aged younger than 3 months presenting with numerous small hemangiomas, ranging from 2 mm to 2 cm in size.2 This condition is usually limited to the skin, but it sometimes affects internal organs resulting in disseminated neonatal hemangiomatosis that can affect multiple organ systems, most commonly the liver, and less commonly, the heart, lung, and intestine. Most infants with significant liver involvement present with the triad of hepatomegaly, anemia, and congestive heart failure before age 4 months. Although the patient did not have hepatomegaly on physical exam, this did not rule out the presence of a hepatic hemangioma. An abdominal ultrasound with Doppler studies must be conducted to exclude internal hemangioma.2
Kasabach-Merritt phenomenon, a life-threatening complication characterized by severe thrombocytopenia and coagulopathy, also should be excluded. Although children with large focal hemangiomas were once thought to be at risk for this complication, Kasabach Merritt is now known not to be associated with true infantile hemangiomas, but rather with 2 other rare vascular tumors that occur during infancy: kaposiform hemangioendothelioma (KHE) and tufted angioma. Kaposiform hemangioendothelioma lesions have a violaceous color with a tumor-like, nodular growth that may rapidly extend into the deep soft tissues and bone. Tufted angiomas have a similar nodular appearance but flattened center, often with hirsutism and tenderness to palpation. The patient’s lesions showed features of typical hemangiomas with no isolated mass, violaceous appearance, or tenderness.
In Kasabach-Merritt phenomenon, patients have either tufted angiomas or, more commonly, KHE in the presence of thrombocytopenia because of the sequestration of platelets within the tumor. In addition to thrombocytopenia, the patient may also have coagulopathy similar to disseminated intravascular coagulation with low fibrinogen and elevated D-dimer levels. Treatment includes surgery, if possible, or medical therapy with sirolimus, steroids, and interferon. In patients with profound thrombocytopenia or coagulopathy, one must also stabilize the patient hemodynamically with fresh frozen plasma or cryoprecipitate.
This child’s lesions were organized in a segmental pattern typical of PHACE syndrome. PHACE syndrome should be suspected in a child presenting with segmental hemangiomas, which are plaque-like hemangiomas restricted to a certain region of the skin, such as the face (Table 2). PHACE is an acronym for the various types of clinical findings present with this condition, including posterior fossa abnormalities, large segmental facial hemangiomas, arterial/cerebrovascular abnormalities, coarctation of the aorta, eye anomalies, and possibly sternal defects.3 In order to meet the diagnostic criteria of PHACE syndrome, a patient must have segmental facial hemangiomas in the presence of one or more associated anomalies, most commonly structural or vascular anomalies of the brain.
Segmental hemangiomas are usually associated with more complications and a worse outcome, especially in Hispanic patients such as this patient.4 The infant’s intermittent respiratory distress raised concerns for an airway hemangioma, a common finding in patients with segmental hemangiomas in a beard distribution occupying the preauricular region, chin, lower lip, and neck areas.5 Although the developmental mechanism is still unknown, it is speculated that the ipsilateral nature of the PHACE anomalies and associated hemangiomas are attributed to a regional insult during embryogenesis resulting in developmental field defects.6
Immediately after admitting the patient, an echocardiogram was conducted in order to investigate the patient’s systolic murmur, and a benign functional ventricular septal defect was detected. Next, an ultrasound of the patient’s face was conducted because of the presence of the large subcutaneous mass on the right cheek. A large parotid gland hemangioma was detected, which is a common benign finding in patients with preauricular hemangiomas.2 No airway hemangiomas were detected via ultrasound, indicating that the patient’s intermittent respiratory distress was likely from the ulcerations on her nose rather than a hemangioma restricting air movement.
Because of the risk of hepatic hemangiomas in a patient with multiple cutaneous hemangiomas, an abdominal ultrasound with Doppler studies was performed. Although no hepatic lesions were noted, excluding visceral hemangiomatosis, grade 2 hydronephrosis of the left kidney and a left ureterocele were incidentally detected.
Lab studies showed a platelet count of 451,000, a normal value that remained stable throughout the patient’s hospitalization. Coagulation studies also showed normal fibrinogen and D-dimer levels, which excluded Kasabach Merritt.
In order to screen for PHACE syndrome, magnetic resonance imaging and magnetic resonance angiography of the infant’s head and neck were conducted, but did not show cerebellar or cerebrovascular abnormalities. However, an intraocular extension of her superficial hemangioma was seen, and a large branch of the facial artery was noted to be feeding her facial hemangiomas. The echocardiogram also ruled out cardiac anomalies associated with PHACE syndrome, specifically coarctation of the aorta.
The child’s evaluation excluded the possibility of anomalies associated with PHACE syndrome as well as Kasabach-Merritt syndrome and disseminated hemangiomatosis. She was diagnosed with segmental infantile hemangiomas, including a large rapidly growing parotic hemangioma and right eyelid hemangioma without PHACE.
Treatment and management
Propranolol is the only approved treatment for complicated infantile hemangiomas. The mechanisms of action of propranolol are not fully understood. Vasoconstriction, down-regulation of proangiogenic factors such as vascular endothelial growth factor, and the triggering of apoptosis of capillary endothelial cells all may play a role in regression of hemangiomas.7
The patient was started on 1 mg/kg/day of propranolol, lower than the recommended dose of 2 mg/kg/day to 3 mg/kg/day because of her small size and fragility, and her hemangiomas decreased progressively in size throughout her weeklong hospital stay. Her oral intake also improved, and she was discharged with orders to follow up with her pediatrician and dermatologist.
On a 4-month follow-up appointment with Dermatology, the patient’s hemangiomas had decreased in size, but she still experienced intermittent respiratory distress especially on days she did not take propranolol, as per parents’ report. The dermatologist subsequently increased her propranolol to 2 mg/kg/day.8 Ophthalmology was involved in the management of this child because of extension of the patient’s hemangioma onto her right eyelid and concerns regarding the development of obstructive amblyopia and/or astigmatism.
Most hemangiomas treated with oral propranolol decrease dramatically over 3 to 4 months, but parotid hemangiomas are often somewhat resistant to medical therapy. Moreover, early intervention is important, because surgical excision is not usually an option due to the risk of damaging the facial nerve.2
This child demonstrates the importance of a multidisciplinary approach to the evaluation of patients with segmental hemangiomas, particularly on the head and neck. Although propranolol provides a safe, approved option for therapy, the mechanism of action is still a mystery and extensive research into this subject will help clinicians provide targeted, effective therapy for patients suffering from complicated hemangiomas.
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5. Orlow SJ, Isakoff MS, Blei F. Increased risk of symptomatic hemangiomas of the airway in association with cutaneous hemangiomas in a 'beard' distribution. J Pediatr. 1997;131(4):643-646.
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7. Peridis S, Pilgrim G, Athanasopoulos I, Parpounas K. A meta-analysis on the effectiveness of propranolol for the treatment of infantile airway haemangiomas. Int J Pediatr Otorhinolaryngol. 2011;75(4):455-460.
8. Frieden IJ, Drolet BA. Propranolol for infantile hemangiomas: promise, peril, pathogenesis. Pediatr Dermatol. 2009;26(5):642-644.