Department of Otorhinolaryngology - Head and Neck Surgery

McGovern Medical School

No More Surgery for Airway Hemangioma?

Two years ago a group of French physicians, Leaute-Labreze et al. reported their spectacular results in treating infantile hemangiomas with oral propranolol, an antihypertensive drug.  This very recent and serendipitous discovery seems to change the direction of the treatment of this most common tumor of infancy dramatically.

Infantile hemangioma is a benign vascular tumor with a self-limiting course consisting of a proliferative phase lasting for three to nine months followed by an involution period. It usually involves the skin and subcutaneous tissues. However, it can occur in the airway, mostly in subglottic area or trachea, and becomes potentially life threatening. In subglottic hemangioma, the child is typically asymptomatic at birth, then becomes symptomatic with inspiratory or biphasic stridor in the first few months of age and can lead to respiratory difficulty. Because this condition can cause life-threatening airway compromise, it often requires urgent treatment.

Multiple treatment modalities have been proposed in the management of airway hemangiomas. These traditional modalities include tracheotomy, systemic steroids, intralesional steroid injection with intubation, interferon or vincristine therapy, laser, or open surgical excision. But the problem is that none of these is perfect and all of them have potentially severe adverse effects in infants. Therefore, the new discovery of a dramatic response to propranolol may mark the end of all other modalities.

All treatment modalities aim to reduce the size of the lesion while remaining tracheotomy-free. But sometimes a patient might need a tracheotomy to secure the airway without manipulating the subglottic region and allowing a wait-and-watch policy. However, this has high morbidity and mortality rate in infants. Mortality usually occurs because of the accidental decannulation and has a rate of 1-2%.

Long term systemic steroid therapy has limited benefits and a high rate of adverse effects. It can cause Cushing syndrome with typical appearance, hirsutism, hypertension, growth retardation, immunosuppression, cardiomyopathy, delayed wound healing and increased infection risk. Intralesional injection of steroid has also been reported as successful but the patients need intubation and ICU admission. Interferon injection is associated with various side effects including spastic diplegia, malaise, neutropenia, and liver enzyme elevations. Systemic chemotherapeutics, like vincristine, have been described in life threatening cases, but they can cause significant neurologic side effects such as peripheral neuropathy. In small lesions laser can be useful but it can cause secondary scarring and laryngeal stenosis.

Open surgical excision was first described in 1949 and has been the preferred treatment option in many centers–especially for patients with bilateral or circumferential lesions.  It may be done in single or two stages and has a relatively high success rate. However, it requires open surgery in a delicate infant larynx, and might require intubation or tracheotomy depending on the staging of the surgery.

In 2008, Leaute-Labreze et al. reported very dramatic success in the treatment of cutaneous hemangiomas with propranolol in 11 patients. They described a rapid onset of action propranolol with visible changes to the hemangiomas in the first day of the treatment. This very first report was a turning point and is changing the treatment strategies used to date. This discovery caused a rush of interested physicians to identify appropriate uses for propranolol in hemangiomas located in problematic areas such as airway. The first report of successful treatment of airway hemangioma has appeared last year; Denoyelle at al. reported 2 infants with subglottic and cutaneous hemangiomas, which were resistant to other established medical treatments. Both patients’ subglottic hemangiomas responded dramatically to systemic propranolol. Several months later, another story of success was reported by Buckmiller et al. on a 2-year-old child with subglottic and tracheal hemangiomas. Within 6 weeks of oral propranolol (2mg/kg/day) her airway compromise was eliminated and she had complete resolution of endoscopically  visible disease. No side effects from propranolol occurred. They proposed that oral propranolol should be considered for use in airway hemangiomas. Jephson et al. has also described successful treatment with propranolol, of a stridolous 4 month-old girl with a 95% obstructing subglottic hemangioma. This was achieved without need for tracheostomy or any other surgical intervention, and with no reported side effects.

Propranolol has been traditionally used in children with hypertension or in certain psychological conditions and has a well-documented safety and side effect profile. Potential side effects are bradycardia, hypotension, bronchospasm, reduced physiological responses to hypoglycemia, fatigue and gastrointestinal irritation. But these are quite rare and tend to be seen at doses over 2 mg/kg/day. The patient is evaluated by pediatric cardiology team; in the absence of cardiac conditions, reactive airway disease or other pulmonary conditions, therapy is initiated. Some authors recommend routine echocardiogram but others save this workup for the patients with pulmonary or cardiac conditions or severe prematurity. It is recommended to use 2 mg/kg/day divided into three doses but further studies will be needed to ascertain the most effective dosing regimen. It is continued through the proliferative phase or until a plateau of improvement occurs. 

All of the reports to date strongly suggest employing propranolol for the treatment of problematic airway hemangiomas due to its efficiency, limited side effect profile and rapid response rate. Although the long-term results of propranolol treatment in infant remain unclear, we are about to witness a historical event in the treatment of subglottic hemangioma as this treatment approaches becoming the first-line treatment for this condition.

References

Leaute-Labreze C, de la Roque ED, Hubiche T, Boralevi F. Propranolol for severe hemangiomas in infancy. N Engl J Med; 358 (2008):2649-2651. (web link)

Siegfried EC, Keenan WJ, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med; 359 (2008): 2846-2847. (web link)

Denoyelle F, Lebaulanger N, Enjolras O, Harris R, Gilles R, Garabedian EN. Role of propranolol in the therapeutic strategy of infantile laryngotracheal haemangioma. Int J Pediatr Otorhinolaryngol; 73 (2009): 1168-1172. (web link)

Buckmiller L, Dyamenahalli U, Richter GT. Propranolol for airway hemangiomas: Case report of novel treatment. Laryngoscope; 119 (2009): 2051-2054.  (web link)

Jephson CG, Manunza F, Syed S, Nikki AM, Harper J, Hartley BEJ. Succesful treatment of isolated haemangioma with propranolol alone. Int J Pediatr Otorhinolaryngol; 73 (2009): 1821-1823.  (web link)

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