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Infantile hemangiomas: New insights into pathogenesis

MAUI, HAWAII – Placental anomalies emerged as a major risk factor for infantile hemangiomas in the first large, prospective study examining the incidence and outcomes of these common vascular abnormalities.

The study included 594 babies born in San Diego who were examined by pediatric dermatologists within the first 48 hours of life and followed prospectively through 9 months of age (J. Pediatr. 2012;161:240-5).

Overall, 4.5% of babies developed infantile hemangiomas (IHs), the most common vascular tumors of childhood, by age 3 months. One of the major unexpected findings was that 53% of the lesions were located on the trunk. A mere 12% in this prospective study were on the head and neck, the locations dermatologists have traditionally been taught that most IHs are to be found, pediatric dermatologist Sheila Fallon Friedlander noted.

Dr. Sheila F. Friedlander

Another surprise: 91% of the IHs were focal, and 23% were abortive/telangiectasic. In other words, most are "not that big or troublesome," according to Dr. Friedlander, who was senior author of the study.

Indeed, only 1 of 34 lesions – a segmental lesion on the hand – required therapeutic intervention.

"This study tells us there’s a wide spectrum of presentation. The patients you see, the ones who come in with a problem, are just the tip of the iceberg. Many infantile hemangiomas that occur are just not a big issue," stressed Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego, and president of the Society for Pediatric Dermatology.

Placenta previa or other placental abnormalities were present in 35% of deliveries of children who subsequently developed IH. The other significant risk factors for IHs in this large study, as in previous studies, were extreme prematurity and white race.

The observation of a high rate of placental abnormalities in kids with IH figured prominently in a recent update by Dr. Friedlander and her coworkers on the pathogenesis and treatment of IH (Pediatrics 2013;131:99-108). One theory as to the origin of IHs holds that the lesions consist of embolized placental tissue sheared off during pregnancy. IHs and placental tissue share in common several surface markers of tissue of chorionic villous mesenchymal core origin: notably, glucose transporter–1 and hypoxia-inducible factor. DNA clustering analyses conducted by other investigators are consistent with the placental embolization theory.

"There’s lots of evidence that if infantile hemangiomas and placenta are not the same tissue, they at least seem to be first cousins," Dr. Friedlander said at the seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A second theory holds that IHs are the result of a somatic mutation in the gene mediating vascular endothelial growth factor–1, which is responsible for putting the brakes on the proliferation of endothelial cells.

The third theory is that hypoxic cells in the placenta or fetal tissue produce HIF to send a message to the bone marrow that they need more oxygen. The bone marrow responds by generating more endothelial progenitor cells, which then home in and proliferate at the hypoxic site. Support for this theory comes from the observation that babies with IHs have increased numbers of circulating endothelial progenitor cells, the pediatric dermatologist continued.

Although the large San Diego study indicates that the great majority of IHs don’t require treatment, the current thinking is to act quickly in the minority that do, particularly now that oral propranolol is firmly established as a treatment of unprecedented effectiveness and safety when lesions warrant systemic therapy.

"It’s the inclination of many primary care physicians to wait and see what’s going to happen with these lesions. That’s not a good idea because it will often result in permanent cosmetic disfigurement. You want to get in there before the damage is done," Dr. Friedlander emphasized.

Early treatment is especially important in high-risk areas, including the central face and periorbital and oral areas, she added.

Dr. Friedlander reported having no relevant financial conflicts. The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

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MAUI, HAWAII – Placental anomalies emerged as a major risk factor for infantile hemangiomas in the first large, prospective study examining the incidence and outcomes of these common vascular abnormalities.

The study included 594 babies born in San Diego who were examined by pediatric dermatologists within the first 48 hours of life and followed prospectively through 9 months of age (J. Pediatr. 2012;161:240-5).

Overall, 4.5% of babies developed infantile hemangiomas (IHs), the most common vascular tumors of childhood, by age 3 months. One of the major unexpected findings was that 53% of the lesions were located on the trunk. A mere 12% in this prospective study were on the head and neck, the locations dermatologists have traditionally been taught that most IHs are to be found, pediatric dermatologist Sheila Fallon Friedlander noted.

Dr. Sheila F. Friedlander

Another surprise: 91% of the IHs were focal, and 23% were abortive/telangiectasic. In other words, most are "not that big or troublesome," according to Dr. Friedlander, who was senior author of the study.

Indeed, only 1 of 34 lesions – a segmental lesion on the hand – required therapeutic intervention.

"This study tells us there’s a wide spectrum of presentation. The patients you see, the ones who come in with a problem, are just the tip of the iceberg. Many infantile hemangiomas that occur are just not a big issue," stressed Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego, and president of the Society for Pediatric Dermatology.

Placenta previa or other placental abnormalities were present in 35% of deliveries of children who subsequently developed IH. The other significant risk factors for IHs in this large study, as in previous studies, were extreme prematurity and white race.

The observation of a high rate of placental abnormalities in kids with IH figured prominently in a recent update by Dr. Friedlander and her coworkers on the pathogenesis and treatment of IH (Pediatrics 2013;131:99-108). One theory as to the origin of IHs holds that the lesions consist of embolized placental tissue sheared off during pregnancy. IHs and placental tissue share in common several surface markers of tissue of chorionic villous mesenchymal core origin: notably, glucose transporter–1 and hypoxia-inducible factor. DNA clustering analyses conducted by other investigators are consistent with the placental embolization theory.

"There’s lots of evidence that if infantile hemangiomas and placenta are not the same tissue, they at least seem to be first cousins," Dr. Friedlander said at the seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A second theory holds that IHs are the result of a somatic mutation in the gene mediating vascular endothelial growth factor–1, which is responsible for putting the brakes on the proliferation of endothelial cells.

The third theory is that hypoxic cells in the placenta or fetal tissue produce HIF to send a message to the bone marrow that they need more oxygen. The bone marrow responds by generating more endothelial progenitor cells, which then home in and proliferate at the hypoxic site. Support for this theory comes from the observation that babies with IHs have increased numbers of circulating endothelial progenitor cells, the pediatric dermatologist continued.

Although the large San Diego study indicates that the great majority of IHs don’t require treatment, the current thinking is to act quickly in the minority that do, particularly now that oral propranolol is firmly established as a treatment of unprecedented effectiveness and safety when lesions warrant systemic therapy.

"It’s the inclination of many primary care physicians to wait and see what’s going to happen with these lesions. That’s not a good idea because it will often result in permanent cosmetic disfigurement. You want to get in there before the damage is done," Dr. Friedlander emphasized.

Early treatment is especially important in high-risk areas, including the central face and periorbital and oral areas, she added.

Dr. Friedlander reported having no relevant financial conflicts. The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Placental anomalies emerged as a major risk factor for infantile hemangiomas in the first large, prospective study examining the incidence and outcomes of these common vascular abnormalities.

The study included 594 babies born in San Diego who were examined by pediatric dermatologists within the first 48 hours of life and followed prospectively through 9 months of age (J. Pediatr. 2012;161:240-5).

Overall, 4.5% of babies developed infantile hemangiomas (IHs), the most common vascular tumors of childhood, by age 3 months. One of the major unexpected findings was that 53% of the lesions were located on the trunk. A mere 12% in this prospective study were on the head and neck, the locations dermatologists have traditionally been taught that most IHs are to be found, pediatric dermatologist Sheila Fallon Friedlander noted.

Dr. Sheila F. Friedlander

Another surprise: 91% of the IHs were focal, and 23% were abortive/telangiectasic. In other words, most are "not that big or troublesome," according to Dr. Friedlander, who was senior author of the study.

Indeed, only 1 of 34 lesions – a segmental lesion on the hand – required therapeutic intervention.

"This study tells us there’s a wide spectrum of presentation. The patients you see, the ones who come in with a problem, are just the tip of the iceberg. Many infantile hemangiomas that occur are just not a big issue," stressed Dr. Friedlander, professor of clinical pediatrics and medicine at the University of California, San Diego, and president of the Society for Pediatric Dermatology.

Placenta previa or other placental abnormalities were present in 35% of deliveries of children who subsequently developed IH. The other significant risk factors for IHs in this large study, as in previous studies, were extreme prematurity and white race.

The observation of a high rate of placental abnormalities in kids with IH figured prominently in a recent update by Dr. Friedlander and her coworkers on the pathogenesis and treatment of IH (Pediatrics 2013;131:99-108). One theory as to the origin of IHs holds that the lesions consist of embolized placental tissue sheared off during pregnancy. IHs and placental tissue share in common several surface markers of tissue of chorionic villous mesenchymal core origin: notably, glucose transporter–1 and hypoxia-inducible factor. DNA clustering analyses conducted by other investigators are consistent with the placental embolization theory.

"There’s lots of evidence that if infantile hemangiomas and placenta are not the same tissue, they at least seem to be first cousins," Dr. Friedlander said at the seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

A second theory holds that IHs are the result of a somatic mutation in the gene mediating vascular endothelial growth factor–1, which is responsible for putting the brakes on the proliferation of endothelial cells.

The third theory is that hypoxic cells in the placenta or fetal tissue produce HIF to send a message to the bone marrow that they need more oxygen. The bone marrow responds by generating more endothelial progenitor cells, which then home in and proliferate at the hypoxic site. Support for this theory comes from the observation that babies with IHs have increased numbers of circulating endothelial progenitor cells, the pediatric dermatologist continued.

Although the large San Diego study indicates that the great majority of IHs don’t require treatment, the current thinking is to act quickly in the minority that do, particularly now that oral propranolol is firmly established as a treatment of unprecedented effectiveness and safety when lesions warrant systemic therapy.

"It’s the inclination of many primary care physicians to wait and see what’s going to happen with these lesions. That’s not a good idea because it will often result in permanent cosmetic disfigurement. You want to get in there before the damage is done," Dr. Friedlander emphasized.

Early treatment is especially important in high-risk areas, including the central face and periorbital and oral areas, she added.

Dr. Friedlander reported having no relevant financial conflicts. The SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

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