Propranolol Considered Standard of Care for Infantile Hemangiomas

SAN DIEGO – There are currently no Food and Drug Administration–approved treatments for infantile hemangiomas, but propranolol appears to be the current standard of care, Dr. Alfie Krol said at the annual meeting of the American Academy of Dermatology.

Since 2008, more than 200 journal articles have been published regarding the use of propranolol for hemangiomas in children, and "initial results are excellent – not just stabilization but shrinkage of the hemangioma occurs, and overall it’s safe," said Dr. Krol, professor of dermatology and pediatrics at Oregon Health and Science University in Portland. "There are some reports of hypoglycemia, which is the most common significant side effect."

Other adverse reactions reported include disturbed sleep, cool extremities, somnolence, hyperkalemia, gastrointestinal esophageal reflux disease, and dental caries. "Overall it’s been well tolerated," Dr. Krol said. "One of the concerning potential side effects is bronchospasm in patients who have a family history of asthma. We haven’t seen that in our center, but it’s something to watch out for."

The dose range is 1-3 mg/kg per day divided b.i.d. or t.i.d. The usual target dose is 2 mg/kg per day. "We don’t know the exact length of time that you need to treat," Dr. Krol said. "In younger patients, it’s likely that 6 months is the minimum because there are reports of regrowth if you discontinue prior to 6 months of active treatment. We have seen that in our center."

Dr. Krol noted that there is currently no clear consensus as to whether to initiate propranolol on an inpatient or outpatient basis. "There are some pediatric dermatologists who admit all patients to start treatment, and they usually do a rapid escalation of the dose from 1-2 mg/kg per day over 48 hours," Dr. Krol said. "Also, some centers have cardiologists see every patient and do echocardiograms on every patient prior to starting therapy. What is clear is that all patients need vital sign monitoring, EKG, cardiac auscultation, and monitoring of vital signs after initial dosing and dose escalations for a minimum of 2 hours on initial visits until the target dose is achieved."

At Oregon Health and Science University, outpatient initiation is done in the pediatric dermatology clinic in the majority of cases, "unless it’s a life- or sight-threatening lesion," Dr. Krol said. "We start at 0.5 mg/kg per day and increase weekly to 1 mg/kg per day and then 2 mg/kg per day over 2 weeks, with appropriate monitoring at each visit."

Rebound can occur, "but certainly not in all patients," he continued. "When it does occur, it often is only partial regrowth. [Propranolol] can shrink fully grown lesions that are no longer proliferating, and there seem to be site-specific effects. Periocular and parotid lesions seem to respond exceedingly well, while nasal tip lesions seem to be less responsive. Overall this drug works very well. The initial safety seems quite good, and overall [propranolol] seems to have replaced oral steroids as the initial therapy. Our comfort level and the overall efficacy of the drug would indicate that most pediatric dermatologists are using this as first-line therapy for hemangiomas of infancy."

In the largest published study to date, researchers in Spain and Argentina conducted a multicenter trial of 71 patients who received a propranolol dose of 2 mg/kg per day for at least 12 weeks (Pediatr. Dermatol. 2011;28:108-14). They found that the effect of propranolol occurred rapidly, usually within 4 weeks. The main side effect in this study was agitated sleep, which occurred in 10 of the 71 patients (14%).

The drug also appears to work beyond the proliferation phase. In a multicenter, retrospective study, researchers from eight centers enrolled 49 patients with hemangiomas that had ceased growth or patients aged 12 months or older (Pediatr. Dermatol.2011;28:94-8). A visual analog scale (VAS) of photographs was used to determine improvement.

The duration of therapy ranged from 1 to 8 months, for a mean of 3.6 months. The VAS score was reduced from 6.8 to 2.6. No significant side effects were reported, and the researchers concluded that propranolol is effective in treating hemangiomas in the postproliferative phase and should be considered first-line therapy in that setting.

In another published study conducted at the University of Miami and Miami Children’s Hospital, researchers compared the use of propranolol with corticosteroids in 110 patients with infantile hemangiomas (Arch. Dermatol. 2011;147:1371-6). They found that 82% of patients in the propranolol group improved by 75% or more, compared with 29% of patients in the steroid group. "That’s a significant improvement over the use of steroids alone," Dr. Krol commented.

One patient on propranolol had hypoglycemia, but all patients in the steroid group had at least one adverse event. The researchers also found propranolol therapy was about half the cost of steroid therapy ($205 for 7.9 months vs. $416 for 5.2 months, respectively). They concluded that propranolol should be considered a first-line therapy for infantile hemangiomas.

He said that larger, long-term studies "are needed to identify any potentially serious as well as long-term safety questions."

Dr. Krol disclosed that he is a paid investigator for Pierre Fabre.

SAN DIEGO – There are currently no Food and Drug Administration–approved treatments for infantile hemangiomas, but propranolol appears to be the current standard of care, Dr. Alfie Krol said at the annual meeting of the American Academy of Dermatology.

Since 2008, more than 200 journal articles have been published regarding the use of propranolol for hemangiomas in children, and "initial results are excellent – not just stabilization but shrinkage of the hemangioma occurs, and overall it’s safe," said Dr. Krol, professor of dermatology and pediatrics at Oregon Health and Science University in Portland. "There are some reports of hypoglycemia, which is the most common significant side effect."

Other adverse reactions reported include disturbed sleep, cool extremities, somnolence, hyperkalemia, gastrointestinal esophageal reflux disease, and dental caries. "Overall it’s been well tolerated," Dr. Krol said. "One of the concerning potential side effects is bronchospasm in patients who have a family history of asthma. We haven’t seen that in our center, but it’s something to watch out for."

The dose range is 1-3 mg/kg per day divided b.i.d. or t.i.d. The usual target dose is 2 mg/kg per day. "We don’t know the exact length of time that you need to treat," Dr. Krol said. "In younger patients, it’s likely that 6 months is the minimum because there are reports of regrowth if you discontinue prior to 6 months of active treatment. We have seen that in our center."

Dr. Krol noted that there is currently no clear consensus as to whether to initiate propranolol on an inpatient or outpatient basis. "There are some pediatric dermatologists who admit all patients to start treatment, and they usually do a rapid escalation of the dose from 1-2 mg/kg per day over 48 hours," Dr. Krol said. "Also, some centers have cardiologists see every patient and do echocardiograms on every patient prior to starting therapy. What is clear is that all patients need vital sign monitoring, EKG, cardiac auscultation, and monitoring of vital signs after initial dosing and dose escalations for a minimum of 2 hours on initial visits until the target dose is achieved."

At Oregon Health and Science University, outpatient initiation is done in the pediatric dermatology clinic in the majority of cases, "unless it’s a life- or sight-threatening lesion," Dr. Krol said. "We start at 0.5 mg/kg per day and increase weekly to 1 mg/kg per day and then 2 mg/kg per day over 2 weeks, with appropriate monitoring at each visit."

Rebound can occur, "but certainly not in all patients," he continued. "When it does occur, it often is only partial regrowth. [Propranolol] can shrink fully grown lesions that are no longer proliferating, and there seem to be site-specific effects. Periocular and parotid lesions seem to respond exceedingly well, while nasal tip lesions seem to be less responsive. Overall this drug works very well. The initial safety seems quite good, and overall [propranolol] seems to have replaced oral steroids as the initial therapy. Our comfort level and the overall efficacy of the drug would indicate that most pediatric dermatologists are using this as first-line therapy for hemangiomas of infancy."

In the largest published study to date, researchers in Spain and Argentina conducted a multicenter trial of 71 patients who received a propranolol dose of 2 mg/kg per day for at least 12 weeks (Pediatr. Dermatol. 2011;28:108-14). They found that the effect of propranolol occurred rapidly, usually within 4 weeks. The main side effect in this study was agitated sleep, which occurred in 10 of the 71 patients (14%).

The drug also appears to work beyond the proliferation phase. In a multicenter, retrospective study, researchers from eight centers enrolled 49 patients with hemangiomas that had ceased growth or patients aged 12 months or older (Pediatr. Dermatol.2011;28:94-8). A visual analog scale (VAS) of photographs was used to determine improvement.

The duration of therapy ranged from 1 to 8 months, for a mean of 3.6 months. The VAS score was reduced from 6.8 to 2.6. No significant side effects were reported, and the researchers concluded that propranolol is effective in treating hemangiomas in the postproliferative phase and should be considered first-line therapy in that setting.

In another published study conducted at the University of Miami and Miami Children’s Hospital, researchers compared the use of propranolol with corticosteroids in 110 patients with infantile hemangiomas (Arch. Dermatol. 2011;147:1371-6). They found that 82% of patients in the propranolol group improved by 75% or more, compared with 29% of patients in the steroid group. "That’s a significant improvement over the use of steroids alone," Dr. Krol commented.

One patient on propranolol had hypoglycemia, but all patients in the steroid group had at least one adverse event. The researchers also found propranolol therapy was about half the cost of steroid therapy ($205 for 7.9 months vs. $416 for 5.2 months, respectively). They concluded that propranolol should be considered a first-line therapy for infantile hemangiomas.

He said that larger, long-term studies "are needed to identify any potentially serious as well as long-term safety questions."

Dr. Krol disclosed that he is a paid investigator for Pierre Fabre.

SAN DIEGO – There are currently no Food and Drug Administration–approved treatments for infantile hemangiomas, but propranolol appears to be the current standard of care, Dr. Alfie Krol said at the annual meeting of the American Academy of Dermatology.

Since 2008, more than 200 journal articles have been published regarding the use of propranolol for hemangiomas in children, and "initial results are excellent – not just stabilization but shrinkage of the hemangioma occurs, and overall it’s safe," said Dr. Krol, professor of dermatology and pediatrics at Oregon Health and Science University in Portland. "There are some reports of hypoglycemia, which is the most common significant side effect."

Other adverse reactions reported include disturbed sleep, cool extremities, somnolence, hyperkalemia, gastrointestinal esophageal reflux disease, and dental caries. "Overall it’s been well tolerated," Dr. Krol said. "One of the concerning potential side effects is bronchospasm in patients who have a family history of asthma. We haven’t seen that in our center, but it’s something to watch out for."

The dose range is 1-3 mg/kg per day divided b.i.d. or t.i.d. The usual target dose is 2 mg/kg per day. "We don’t know the exact length of time that you need to treat," Dr. Krol said. "In younger patients, it’s likely that 6 months is the minimum because there are reports of regrowth if you discontinue prior to 6 months of active treatment. We have seen that in our center."

Dr. Krol noted that there is currently no clear consensus as to whether to initiate propranolol on an inpatient or outpatient basis. "There are some pediatric dermatologists who admit all patients to start treatment, and they usually do a rapid escalation of the dose from 1-2 mg/kg per day over 48 hours," Dr. Krol said. "Also, some centers have cardiologists see every patient and do echocardiograms on every patient prior to starting therapy. What is clear is that all patients need vital sign monitoring, EKG, cardiac auscultation, and monitoring of vital signs after initial dosing and dose escalations for a minimum of 2 hours on initial visits until the target dose is achieved."

At Oregon Health and Science University, outpatient initiation is done in the pediatric dermatology clinic in the majority of cases, "unless it’s a life- or sight-threatening lesion," Dr. Krol said. "We start at 0.5 mg/kg per day and increase weekly to 1 mg/kg per day and then 2 mg/kg per day over 2 weeks, with appropriate monitoring at each visit."

Rebound can occur, "but certainly not in all patients," he continued. "When it does occur, it often is only partial regrowth. [Propranolol] can shrink fully grown lesions that are no longer proliferating, and there seem to be site-specific effects. Periocular and parotid lesions seem to respond exceedingly well, while nasal tip lesions seem to be less responsive. Overall this drug works very well. The initial safety seems quite good, and overall [propranolol] seems to have replaced oral steroids as the initial therapy. Our comfort level and the overall efficacy of the drug would indicate that most pediatric dermatologists are using this as first-line therapy for hemangiomas of infancy."

In the largest published study to date, researchers in Spain and Argentina conducted a multicenter trial of 71 patients who received a propranolol dose of 2 mg/kg per day for at least 12 weeks (Pediatr. Dermatol. 2011;28:108-14). They found that the effect of propranolol occurred rapidly, usually within 4 weeks. The main side effect in this study was agitated sleep, which occurred in 10 of the 71 patients (14%).

The drug also appears to work beyond the proliferation phase. In a multicenter, retrospective study, researchers from eight centers enrolled 49 patients with hemangiomas that had ceased growth or patients aged 12 months or older (Pediatr. Dermatol.2011;28:94-8). A visual analog scale (VAS) of photographs was used to determine improvement.

The duration of therapy ranged from 1 to 8 months, for a mean of 3.6 months. The VAS score was reduced from 6.8 to 2.6. No significant side effects were reported, and the researchers concluded that propranolol is effective in treating hemangiomas in the postproliferative phase and should be considered first-line therapy in that setting.

In another published study conducted at the University of Miami and Miami Children’s Hospital, researchers compared the use of propranolol with corticosteroids in 110 patients with infantile hemangiomas (Arch. Dermatol. 2011;147:1371-6). They found that 82% of patients in the propranolol group improved by 75% or more, compared with 29% of patients in the steroid group. "That’s a significant improvement over the use of steroids alone," Dr. Krol commented.

One patient on propranolol had hypoglycemia, but all patients in the steroid group had at least one adverse event. The researchers also found propranolol therapy was about half the cost of steroid therapy ($205 for 7.9 months vs. $416 for 5.2 months, respectively). They concluded that propranolol should be considered a first-line therapy for infantile hemangiomas.

He said that larger, long-term studies "are needed to identify any potentially serious as well as long-term safety questions."

Dr. Krol disclosed that he is a paid investigator for Pierre Fabre.