Case series supports oral itraconazole for infantile hemangiomas

COPENHAGEN – Ever since Dr. Yuping Ran published his initial report of successful treatment of infantile hemangiomas using oral itraconazole, dermatologists from around the world have been bombarding him with the same three questions: Does it really work? Is the treatment safe? What’s the mechanism for the response?

His research has continued at a brisk clip since that preliminary publication (J Dermatol. 2015 Feb;42(2):202-6), so he was able to provide updated answers to those three key questions at the annual congress of the European Academy of Dermatology and Venereology.

Efficacy: His case series is now up to 17 treated patients, average age 3.6 months, with disfiguring or functionally significant infantile hemangiomas. Twelve of the 17 (71%) were successfully treated as defined by 80%-100% improvement that met with the approval of parents and physicians, said Dr. Ran, professor of dermatology at Sichuan University in Chengdu, China.

Treatment was given for an average of 8.8 weeks with oral itraconazole at 5 mg/kg/day. Dr. Ran’s initial serendipitous observation of a therapeutic effect on infantile hemangioma came from a baby he was treating with itraconazole capsules for a Candida albicans infection. He now uses only the oral solution, however, because it’s so much easier for parents to administer.

Safety: “We’ve monitored liver function before, during, and after treatment. It has always been within normal range,” Dr. Ran reported. Roughly 30% of infants have developed mild diarrhea on treatment. This has been readily manageable and hasn’t led to any halt in treatment.

Mechanism of benefit: In vitro studies conducted in Dr. Ran’s laboratory have shown that itraconazole inhibits growth and migration of proliferating human hemangioma epithelial cells, while ketoconazole does not. Moreover, when Dr. Ran and coworkers compared itraconazole to propranolol – a first-line medical treatment for infantile hemangiomas – itraconazole inhibited hemangioma epithelial cells far more efficiently than propranolol. Indeed, in order for propranolol to match itraconazole’s apoptotic effect, the cells had to be exposed to the beta blocker at a concentration that was 10-fold greater than that of itraconazole.

In further studies, Dr. Ran and coworkers have shown that itraconazole downregulates two key pathways in hemangioma cell growth: the hedgehog pathway and the P13K/AKT/mTOR signaling pathway. This is the likely mechanism of therapeutic effect, he said.

Dr. Ran’s studies are supported by the National Natural Science Foundation of China. He reported having no financial conflicts of interest.

[email protected]

COPENHAGEN – Ever since Dr. Yuping Ran published his initial report of successful treatment of infantile hemangiomas using oral itraconazole, dermatologists from around the world have been bombarding him with the same three questions: Does it really work? Is the treatment safe? What’s the mechanism for the response?

His research has continued at a brisk clip since that preliminary publication (J Dermatol. 2015 Feb;42(2):202-6), so he was able to provide updated answers to those three key questions at the annual congress of the European Academy of Dermatology and Venereology.

Efficacy: His case series is now up to 17 treated patients, average age 3.6 months, with disfiguring or functionally significant infantile hemangiomas. Twelve of the 17 (71%) were successfully treated as defined by 80%-100% improvement that met with the approval of parents and physicians, said Dr. Ran, professor of dermatology at Sichuan University in Chengdu, China.

Treatment was given for an average of 8.8 weeks with oral itraconazole at 5 mg/kg/day. Dr. Ran’s initial serendipitous observation of a therapeutic effect on infantile hemangioma came from a baby he was treating with itraconazole capsules for a Candida albicans infection. He now uses only the oral solution, however, because it’s so much easier for parents to administer.

Safety: “We’ve monitored liver function before, during, and after treatment. It has always been within normal range,” Dr. Ran reported. Roughly 30% of infants have developed mild diarrhea on treatment. This has been readily manageable and hasn’t led to any halt in treatment.

Mechanism of benefit: In vitro studies conducted in Dr. Ran’s laboratory have shown that itraconazole inhibits growth and migration of proliferating human hemangioma epithelial cells, while ketoconazole does not. Moreover, when Dr. Ran and coworkers compared itraconazole to propranolol – a first-line medical treatment for infantile hemangiomas – itraconazole inhibited hemangioma epithelial cells far more efficiently than propranolol. Indeed, in order for propranolol to match itraconazole’s apoptotic effect, the cells had to be exposed to the beta blocker at a concentration that was 10-fold greater than that of itraconazole.

In further studies, Dr. Ran and coworkers have shown that itraconazole downregulates two key pathways in hemangioma cell growth: the hedgehog pathway and the P13K/AKT/mTOR signaling pathway. This is the likely mechanism of therapeutic effect, he said.

Dr. Ran’s studies are supported by the National Natural Science Foundation of China. He reported having no financial conflicts of interest.

[email protected]

COPENHAGEN – Ever since Dr. Yuping Ran published his initial report of successful treatment of infantile hemangiomas using oral itraconazole, dermatologists from around the world have been bombarding him with the same three questions: Does it really work? Is the treatment safe? What’s the mechanism for the response?

His research has continued at a brisk clip since that preliminary publication (J Dermatol. 2015 Feb;42(2):202-6), so he was able to provide updated answers to those three key questions at the annual congress of the European Academy of Dermatology and Venereology.

Efficacy: His case series is now up to 17 treated patients, average age 3.6 months, with disfiguring or functionally significant infantile hemangiomas. Twelve of the 17 (71%) were successfully treated as defined by 80%-100% improvement that met with the approval of parents and physicians, said Dr. Ran, professor of dermatology at Sichuan University in Chengdu, China.

Treatment was given for an average of 8.8 weeks with oral itraconazole at 5 mg/kg/day. Dr. Ran’s initial serendipitous observation of a therapeutic effect on infantile hemangioma came from a baby he was treating with itraconazole capsules for a Candida albicans infection. He now uses only the oral solution, however, because it’s so much easier for parents to administer.

Safety: “We’ve monitored liver function before, during, and after treatment. It has always been within normal range,” Dr. Ran reported. Roughly 30% of infants have developed mild diarrhea on treatment. This has been readily manageable and hasn’t led to any halt in treatment.

Mechanism of benefit: In vitro studies conducted in Dr. Ran’s laboratory have shown that itraconazole inhibits growth and migration of proliferating human hemangioma epithelial cells, while ketoconazole does not. Moreover, when Dr. Ran and coworkers compared itraconazole to propranolol – a first-line medical treatment for infantile hemangiomas – itraconazole inhibited hemangioma epithelial cells far more efficiently than propranolol. Indeed, in order for propranolol to match itraconazole’s apoptotic effect, the cells had to be exposed to the beta blocker at a concentration that was 10-fold greater than that of itraconazole.

In further studies, Dr. Ran and coworkers have shown that itraconazole downregulates two key pathways in hemangioma cell growth: the hedgehog pathway and the P13K/AKT/mTOR signaling pathway. This is the likely mechanism of therapeutic effect, he said.

Dr. Ran’s studies are supported by the National Natural Science Foundation of China. He reported having no financial conflicts of interest.

[email protected]