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Nadolol bests propranolol for infantile hemangioma treatment out to 52 weeks
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
of 71 patients showed.
“In clinical practice, we notice that nadolol works very well in terms of controlling the size and the appearance of the hemangioma,” lead study author Elena Pope, MD, MSc, said during the annual meeting of the Society for Pediatric Dermatology. Hence, she and her colleagues were interested in comparing their clinical experience with the standard treatment with propranolol, and designed a prospective, randomized, controlled, double-blinded study, with the aim of proving that “nadolol is noninferior to propranolol, with a margin of noninferiority of 10%.”
Between 2016 and 2020, Dr. Pope and colleagues at two academic Canadian pediatric dermatology centers enrolled 71 infants aged 1-6 months with significant hemangioma that had either the potential for functional impairment or cosmetic deformity, defined as a lesion greater than 1.5 cm on the face or greater than 3 cm on another body part. Treatment consisted of oral propranolol or nadolol in escalating doses up to 2 mg/kg per day. “The blinding portion of the study was for 24 weeks with a follow-up up to 52 weeks,” said Dr. Pope, professor of pediatrics at the University of Toronto and section head of pediatric dermatology at The Hospital for Sick Children, also in Toronto. “After the unblinding at 24 weeks, patients were allowed to switch their intervention if they were not happy with the results.”
Of the 71 patients, 35 received nadolol and 36 received propranolol. The two groups were similar in terms of clinical and demographic characteristics. Their mean age at enrollment was 3.15 months, 80% were female, 61% were White, 20% were Asian, and the rest were from other ethnic backgrounds.
At 24 weeks, the researchers found that the mean size involution was 97.94% in the nadolol group and 89.14% in the propranolol group (P = .005), while the mean color fading on the visual analogue scale (VAS) was 94.47% in the nadolol group and 80.54% in the propranolol group (P < .001). At 52 weeks, the mean size involution was 99.63% in the nadolol group and 93.63% in the propranolol group (P = .001), while the mean VAS color fading was 97.34% in the nadolol group and 87.23% in the propranolol group (P = .001).
According to Dr. Pope, Kaplan-Meir analysis showed that patients in the propranolol group responded slower to treatment (P = .019), while safety data was similar between the two groups. For example, between weeks 25 and 52, 84.2% of patients in the nadolol group experienced an adverse event, compared with 74.2% of patients in the propranolol group (P = .466). The most common respiratory adverse event was upper respiratory tract infection, which affected 87.5% of patients in the nadolol group, compared with 100% of patients in the propranolol group (P = 0.341).
The most common gastrointestinal adverse event was diarrhea, which affected 66.7% of patients in both groups. One patient in the propranolol group was admitted to the hospital with pneumonia and fully recovered. The incident was not suspected to be related to the medication.
“We believe that this data backs up our clinical experience and it may offer an alternative treatment in other centers where patients experience propranolol unresponsiveness, side effects, or intolerance, or where a fast response is needed,” Dr. Pope said. As for the potential cost implications, “nadolol is cheaper than the Hemangiol but comparable with the compounded formulation of propranolol.”
Concern over the safety of nadolol was raised in a case report published in Pediatrics in 2020. Authors from Alberta reported the case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity,” the authors wrote.
In a reply to the authors in the same issue of Pediatrics, Dr. Pope, Cathryn Sibbald, MD, and Erin Chung, PhD, pointed out that postmortem redistribution of medications “is complex and measured postmortem cardiac blood concentrations may be significantly higher than the true blood nadolol concentration at the time of death due to significant diffusion from the peripheral tissues.”
They added that the report did not address “other potential errors such as in compounding, dispensing, and administration of the solution,” they wrote, adding: “Finally, we are aware of a Canadian case of death in an infant receiving propranolol, although the cause of death in that case was unable to be determined (ISMP Canada 2016 Safety Bulletin).We agree with the authors that careful consideration of the risks and benefits of beta-blocker therapy should be employed, parents need to be informed when to discontinue therapy and that further research into the pharmacokinetics and pharmacogenetics of beta-blockers are warranted.”
Following publication of the case report in Pediatrics, Dr. Pope said that the only change she made in her practice was to ask families to temporarily discontinue nadolol if their child had constipation for more than 5 days.
The study was supported by a grant from Physician Services, Inc. Dr. Pope reported having no financial disclosures.
FROM SPD 2021
Married docs remove girl’s lethal facial tumor in ‘excruciatingly difficult’ procedure
In 2019, doctors in London saw a 5-year old girl from rural Ethiopia with an enormous tumor extending from her cheek to her lower jaw. Her name was Negalem and the tumor was a vascular malformation, a life-threatening web of tangled blood vessels.
Surgery to remove it was impossible, the doctors told the foundation advocating for the girl. The child would never make it off the operating table. After a closer examination, the London group still declined to do the procedure, but told the child’s parents and advocates that if anyone was going to attempt this, they’d need to get the little girl to New York.
In New York City, on 64th St. in Manhattan, is the Vascular Birthmark Institute, founded by Milton Waner, MD, who has exclusively treated hemangiomas and vascular malformations for the last 30 years. “I’m the only person in the [United] States whose practice is exclusively [treating] vascular anomalies,” Dr. Waner said in an interview.
Dr. Waner has assembled a multidisciplinary team of experts at the institute’s offices in Lenox Hill – including his wife Teresa O, MD, a facial plastic and reconstructive surgeon and neurospecialist. “People often ask how the hell do you spend so much time with your spouse?” Dr. Waner says. “We work extremely well together. We complement each other.”
Dr. O and Dr. Waner each manage half of the cases at VBI. And in January they received an email about Negalem. After corresponding with the child’s advocate and reviewing images,
The challenge with vascular malformations in children, Dr. Waner said, is that they have a fraction of the blood an adult has. Where adults have an average of 5 L of blood, a child this age has only 1 L. To lose 200 or 300 mL of blood, “that’s 20% or 30% of their blood volume,” Dr. Waner said. So the removal of such a mass, which requires a meticulous dissection around many blood vessels, carries a high risk of the child bleeding out.
There were some logistical hurdles, but the patient arrived in Manhattan in mid-June, at no cost to her family. The medical visa was organized by a volunteer who also work for USAID. Healing the Children Northeast paid for her travel and the Waner Kids Foundation paid for her hotel stay. Lenox Hill Hospital and Northwell Health covered all hospital costs and postsurgery care. And Dr. O and Dr. Waner did the planning, consult visits, and procedure pro bono.
The surgery was possible because of the generosity of several organizations, but the two surgeons still had a limited time to remove the mass. Under different circumstances, and with the luxury of more time, the patient would have undergone several rounds of sclerotherapy. This procedure, done by interventional radiologists, involves injecting a toxin into the blood vessels, which causes them to clot. Done prior to surgery it can help limit bleeding risk.
On June 23, the morning of the surgery, the patient underwent one round of sclerotherapy. However, it didn’t have the intended effect, Dr. Waner said, “because the lesion was just so massive.”
The team had planned several of their moves ahead of time. But this isn’t the sort of surgery you’d find in a textbook. Because it’s such a unique field, Dr. Waner and Dr. O have developed many of their own techniques along the way. This patient was much like the cases they treat every day, only “several orders of magnitudes greater,” Dr. Waner said. “On a scale of 1 to 10 she was a 12.”
The morning of the surgery, “I was very apprehensive,” Dr. Waner recalled. He vividly remembers the girl’s father repeatedly kissing her to say goodbye as she lay on the operating table, fully aware that this procedure was a life-threatening one. And from the beginning there were challenges, like getting her under anesthesia when the anatomy of her mouth, deformed by the tumor, didn’t allow the anesthesiologists to use their typical tubing. Then, once the skin was removed, it became clear how dilated and tangled the involved blood vessels were. There were many vital structures tangled in the anomaly. “The jugular vein was right there. The carotid artery was right there,” Dr. Waner said. It was extremely difficult to delineate and preserve them, he said.
“That’s why we really took our time. We just went very slowly and deliberately,” Dr. O said. The blood vessels were so dilated that their only option was to move painstakingly slow – otherwise a small nick could be devastating.
But even with the slow pace the surgery was “excruciatingly difficult,” Dr. Waner said. And early on in the dissection he wasn’t quite sure they’d make it out. The sclerotherapy hadn’t done much to prevent bleeding. “At one point every millimeter or 2 that we advanced we got into some bleeding,” Dr. Waner said. “Brisk bleeding.”
Once they got into the surgery they also realized that the growth had adhered to the jaw bone. “There were vessels traversing into the bone, which were hard to control,” Dr. O said.
But finally, both doctors realized they’d be able to remove it. With the lesion removed they began the work of reconstruction and reanimation.
The child’s jaw and cheek bone had grown beyond their normal size to support the growth. They had to shave them down to achieve facial symmetry. The tumor had also inhibited much of the child’s facial nerve control. With it gone, Dr. O began the work of finding all the facial nerve branches and assembling them to reanimate the child’s face.
Before medicine, Dr. O trained as an architect, which, according to Dr. Waner, has equipped her with very good spatial awareness – a valuable skill in the surgical reconstruction phase. After seeing a lecture by Dr. Waner, she immediately saw a fit for her unique interest and skill set. She did fellowship training with Dr. Waner in vascular anomalies, and then went on to specialize in facial nerve reanimation. The proof of Dr. O’s expertise is Negalem’s new, beautiful smile, Dr. Waner said.
The surgery drew out over 8 hours, as long as a day of surgeries for the two doctors. When Dr. O finally walked into the waiting room to inform the family of the success, the first words out of the father’s mouth were: “Is my daughter alive?”
A growth like Negalem had is not compatible with a normal life. Dr. Waner’s mantra is that every child has the right to look normal. But this case went beyond aesthetics. If the growth hadn’t been removed, the child was expected to live only 4-6 more years, Dr. Waner said. Without the surgery, she could have suffocated, starved without the ability to swallow, or suffered a fatal bleed.
Dr. O and Dr. Waner are uniquely equipped to do this kind of work, but both are adamant that treating vascular anomalies is a multidisciplinary, multimodal approach. Specialties in anesthesiology, radiology, lasers, facial nerves – they are all critical to these procedures. And often patients with these kinds of lesions require medical and radiologic interventions in addition to surgery. In this particular case, from logistics to post op, “it was a lot of teamwork,” Dr. O said, “a lot of international teams coming together.”
Though extremely difficult, “in the end the result was exactly what we wanted,” Dr. Waner said. Negalem can live a normal life. And as for the surgical duo, both feel very fortunate to do this work. Dr. O said, “I’m honored to have found this specialty and to be able to train with and work with Milton. I’m so happy to do what I do every day.”
A version of this article first appeared on Medscape.com.
In 2019, doctors in London saw a 5-year old girl from rural Ethiopia with an enormous tumor extending from her cheek to her lower jaw. Her name was Negalem and the tumor was a vascular malformation, a life-threatening web of tangled blood vessels.
Surgery to remove it was impossible, the doctors told the foundation advocating for the girl. The child would never make it off the operating table. After a closer examination, the London group still declined to do the procedure, but told the child’s parents and advocates that if anyone was going to attempt this, they’d need to get the little girl to New York.
In New York City, on 64th St. in Manhattan, is the Vascular Birthmark Institute, founded by Milton Waner, MD, who has exclusively treated hemangiomas and vascular malformations for the last 30 years. “I’m the only person in the [United] States whose practice is exclusively [treating] vascular anomalies,” Dr. Waner said in an interview.
Dr. Waner has assembled a multidisciplinary team of experts at the institute’s offices in Lenox Hill – including his wife Teresa O, MD, a facial plastic and reconstructive surgeon and neurospecialist. “People often ask how the hell do you spend so much time with your spouse?” Dr. Waner says. “We work extremely well together. We complement each other.”
Dr. O and Dr. Waner each manage half of the cases at VBI. And in January they received an email about Negalem. After corresponding with the child’s advocate and reviewing images,
The challenge with vascular malformations in children, Dr. Waner said, is that they have a fraction of the blood an adult has. Where adults have an average of 5 L of blood, a child this age has only 1 L. To lose 200 or 300 mL of blood, “that’s 20% or 30% of their blood volume,” Dr. Waner said. So the removal of such a mass, which requires a meticulous dissection around many blood vessels, carries a high risk of the child bleeding out.
There were some logistical hurdles, but the patient arrived in Manhattan in mid-June, at no cost to her family. The medical visa was organized by a volunteer who also work for USAID. Healing the Children Northeast paid for her travel and the Waner Kids Foundation paid for her hotel stay. Lenox Hill Hospital and Northwell Health covered all hospital costs and postsurgery care. And Dr. O and Dr. Waner did the planning, consult visits, and procedure pro bono.
The surgery was possible because of the generosity of several organizations, but the two surgeons still had a limited time to remove the mass. Under different circumstances, and with the luxury of more time, the patient would have undergone several rounds of sclerotherapy. This procedure, done by interventional radiologists, involves injecting a toxin into the blood vessels, which causes them to clot. Done prior to surgery it can help limit bleeding risk.
On June 23, the morning of the surgery, the patient underwent one round of sclerotherapy. However, it didn’t have the intended effect, Dr. Waner said, “because the lesion was just so massive.”
The team had planned several of their moves ahead of time. But this isn’t the sort of surgery you’d find in a textbook. Because it’s such a unique field, Dr. Waner and Dr. O have developed many of their own techniques along the way. This patient was much like the cases they treat every day, only “several orders of magnitudes greater,” Dr. Waner said. “On a scale of 1 to 10 she was a 12.”
The morning of the surgery, “I was very apprehensive,” Dr. Waner recalled. He vividly remembers the girl’s father repeatedly kissing her to say goodbye as she lay on the operating table, fully aware that this procedure was a life-threatening one. And from the beginning there were challenges, like getting her under anesthesia when the anatomy of her mouth, deformed by the tumor, didn’t allow the anesthesiologists to use their typical tubing. Then, once the skin was removed, it became clear how dilated and tangled the involved blood vessels were. There were many vital structures tangled in the anomaly. “The jugular vein was right there. The carotid artery was right there,” Dr. Waner said. It was extremely difficult to delineate and preserve them, he said.
“That’s why we really took our time. We just went very slowly and deliberately,” Dr. O said. The blood vessels were so dilated that their only option was to move painstakingly slow – otherwise a small nick could be devastating.
But even with the slow pace the surgery was “excruciatingly difficult,” Dr. Waner said. And early on in the dissection he wasn’t quite sure they’d make it out. The sclerotherapy hadn’t done much to prevent bleeding. “At one point every millimeter or 2 that we advanced we got into some bleeding,” Dr. Waner said. “Brisk bleeding.”
Once they got into the surgery they also realized that the growth had adhered to the jaw bone. “There were vessels traversing into the bone, which were hard to control,” Dr. O said.
But finally, both doctors realized they’d be able to remove it. With the lesion removed they began the work of reconstruction and reanimation.
The child’s jaw and cheek bone had grown beyond their normal size to support the growth. They had to shave them down to achieve facial symmetry. The tumor had also inhibited much of the child’s facial nerve control. With it gone, Dr. O began the work of finding all the facial nerve branches and assembling them to reanimate the child’s face.
Before medicine, Dr. O trained as an architect, which, according to Dr. Waner, has equipped her with very good spatial awareness – a valuable skill in the surgical reconstruction phase. After seeing a lecture by Dr. Waner, she immediately saw a fit for her unique interest and skill set. She did fellowship training with Dr. Waner in vascular anomalies, and then went on to specialize in facial nerve reanimation. The proof of Dr. O’s expertise is Negalem’s new, beautiful smile, Dr. Waner said.
The surgery drew out over 8 hours, as long as a day of surgeries for the two doctors. When Dr. O finally walked into the waiting room to inform the family of the success, the first words out of the father’s mouth were: “Is my daughter alive?”
A growth like Negalem had is not compatible with a normal life. Dr. Waner’s mantra is that every child has the right to look normal. But this case went beyond aesthetics. If the growth hadn’t been removed, the child was expected to live only 4-6 more years, Dr. Waner said. Without the surgery, she could have suffocated, starved without the ability to swallow, or suffered a fatal bleed.
Dr. O and Dr. Waner are uniquely equipped to do this kind of work, but both are adamant that treating vascular anomalies is a multidisciplinary, multimodal approach. Specialties in anesthesiology, radiology, lasers, facial nerves – they are all critical to these procedures. And often patients with these kinds of lesions require medical and radiologic interventions in addition to surgery. In this particular case, from logistics to post op, “it was a lot of teamwork,” Dr. O said, “a lot of international teams coming together.”
Though extremely difficult, “in the end the result was exactly what we wanted,” Dr. Waner said. Negalem can live a normal life. And as for the surgical duo, both feel very fortunate to do this work. Dr. O said, “I’m honored to have found this specialty and to be able to train with and work with Milton. I’m so happy to do what I do every day.”
A version of this article first appeared on Medscape.com.
In 2019, doctors in London saw a 5-year old girl from rural Ethiopia with an enormous tumor extending from her cheek to her lower jaw. Her name was Negalem and the tumor was a vascular malformation, a life-threatening web of tangled blood vessels.
Surgery to remove it was impossible, the doctors told the foundation advocating for the girl. The child would never make it off the operating table. After a closer examination, the London group still declined to do the procedure, but told the child’s parents and advocates that if anyone was going to attempt this, they’d need to get the little girl to New York.
In New York City, on 64th St. in Manhattan, is the Vascular Birthmark Institute, founded by Milton Waner, MD, who has exclusively treated hemangiomas and vascular malformations for the last 30 years. “I’m the only person in the [United] States whose practice is exclusively [treating] vascular anomalies,” Dr. Waner said in an interview.
Dr. Waner has assembled a multidisciplinary team of experts at the institute’s offices in Lenox Hill – including his wife Teresa O, MD, a facial plastic and reconstructive surgeon and neurospecialist. “People often ask how the hell do you spend so much time with your spouse?” Dr. Waner says. “We work extremely well together. We complement each other.”
Dr. O and Dr. Waner each manage half of the cases at VBI. And in January they received an email about Negalem. After corresponding with the child’s advocate and reviewing images,
The challenge with vascular malformations in children, Dr. Waner said, is that they have a fraction of the blood an adult has. Where adults have an average of 5 L of blood, a child this age has only 1 L. To lose 200 or 300 mL of blood, “that’s 20% or 30% of their blood volume,” Dr. Waner said. So the removal of such a mass, which requires a meticulous dissection around many blood vessels, carries a high risk of the child bleeding out.
There were some logistical hurdles, but the patient arrived in Manhattan in mid-June, at no cost to her family. The medical visa was organized by a volunteer who also work for USAID. Healing the Children Northeast paid for her travel and the Waner Kids Foundation paid for her hotel stay. Lenox Hill Hospital and Northwell Health covered all hospital costs and postsurgery care. And Dr. O and Dr. Waner did the planning, consult visits, and procedure pro bono.
The surgery was possible because of the generosity of several organizations, but the two surgeons still had a limited time to remove the mass. Under different circumstances, and with the luxury of more time, the patient would have undergone several rounds of sclerotherapy. This procedure, done by interventional radiologists, involves injecting a toxin into the blood vessels, which causes them to clot. Done prior to surgery it can help limit bleeding risk.
On June 23, the morning of the surgery, the patient underwent one round of sclerotherapy. However, it didn’t have the intended effect, Dr. Waner said, “because the lesion was just so massive.”
The team had planned several of their moves ahead of time. But this isn’t the sort of surgery you’d find in a textbook. Because it’s such a unique field, Dr. Waner and Dr. O have developed many of their own techniques along the way. This patient was much like the cases they treat every day, only “several orders of magnitudes greater,” Dr. Waner said. “On a scale of 1 to 10 she was a 12.”
The morning of the surgery, “I was very apprehensive,” Dr. Waner recalled. He vividly remembers the girl’s father repeatedly kissing her to say goodbye as she lay on the operating table, fully aware that this procedure was a life-threatening one. And from the beginning there were challenges, like getting her under anesthesia when the anatomy of her mouth, deformed by the tumor, didn’t allow the anesthesiologists to use their typical tubing. Then, once the skin was removed, it became clear how dilated and tangled the involved blood vessels were. There were many vital structures tangled in the anomaly. “The jugular vein was right there. The carotid artery was right there,” Dr. Waner said. It was extremely difficult to delineate and preserve them, he said.
“That’s why we really took our time. We just went very slowly and deliberately,” Dr. O said. The blood vessels were so dilated that their only option was to move painstakingly slow – otherwise a small nick could be devastating.
But even with the slow pace the surgery was “excruciatingly difficult,” Dr. Waner said. And early on in the dissection he wasn’t quite sure they’d make it out. The sclerotherapy hadn’t done much to prevent bleeding. “At one point every millimeter or 2 that we advanced we got into some bleeding,” Dr. Waner said. “Brisk bleeding.”
Once they got into the surgery they also realized that the growth had adhered to the jaw bone. “There were vessels traversing into the bone, which were hard to control,” Dr. O said.
But finally, both doctors realized they’d be able to remove it. With the lesion removed they began the work of reconstruction and reanimation.
The child’s jaw and cheek bone had grown beyond their normal size to support the growth. They had to shave them down to achieve facial symmetry. The tumor had also inhibited much of the child’s facial nerve control. With it gone, Dr. O began the work of finding all the facial nerve branches and assembling them to reanimate the child’s face.
Before medicine, Dr. O trained as an architect, which, according to Dr. Waner, has equipped her with very good spatial awareness – a valuable skill in the surgical reconstruction phase. After seeing a lecture by Dr. Waner, she immediately saw a fit for her unique interest and skill set. She did fellowship training with Dr. Waner in vascular anomalies, and then went on to specialize in facial nerve reanimation. The proof of Dr. O’s expertise is Negalem’s new, beautiful smile, Dr. Waner said.
The surgery drew out over 8 hours, as long as a day of surgeries for the two doctors. When Dr. O finally walked into the waiting room to inform the family of the success, the first words out of the father’s mouth were: “Is my daughter alive?”
A growth like Negalem had is not compatible with a normal life. Dr. Waner’s mantra is that every child has the right to look normal. But this case went beyond aesthetics. If the growth hadn’t been removed, the child was expected to live only 4-6 more years, Dr. Waner said. Without the surgery, she could have suffocated, starved without the ability to swallow, or suffered a fatal bleed.
Dr. O and Dr. Waner are uniquely equipped to do this kind of work, but both are adamant that treating vascular anomalies is a multidisciplinary, multimodal approach. Specialties in anesthesiology, radiology, lasers, facial nerves – they are all critical to these procedures. And often patients with these kinds of lesions require medical and radiologic interventions in addition to surgery. In this particular case, from logistics to post op, “it was a lot of teamwork,” Dr. O said, “a lot of international teams coming together.”
Though extremely difficult, “in the end the result was exactly what we wanted,” Dr. Waner said. Negalem can live a normal life. And as for the surgical duo, both feel very fortunate to do this work. Dr. O said, “I’m honored to have found this specialty and to be able to train with and work with Milton. I’m so happy to do what I do every day.”
A version of this article first appeared on Medscape.com.
Study eyes impact of isotretinoin on triglycerides, other lab measures
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
FROM SPD 2021
Isotretinoin benefits similar in overweight, obese adolescents, and those in normal weight range
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
a retrospective cohort study found.
“Oral isotretinoin is among the most effective treatments for acne and is indicated for the treatment of severe acne or when first-line regimens have failed,” Maggie Tallmadge said at the annual meeting of the Society for Pediatric Dermatology. In adolescents with acne, isotretinoin is prescribed at a dose of 0.5-1 mg/kg per day “with the goal of reaching a cumulative dose of 120-150 mg/kg and clinical clearance with durable remission,” she said. “Most providers do not prescribe a daily dose over 80 mg due to perceived increased risk of side effects, including xerosis, cheilitis, liver dysfunction, and acne flare. However, many adolescents weigh over 80 kg and are therefore effectively underdosed, prolonging treatment time and possibly increasing the risk of side effects due to prolonged therapy.”
To evaluate differences in treatment courses among normal-weight, overweight, and obese adolescents, and the efficacy and safety of treatment, Ms. Tallmadge, a third-year medical student at the Medical College of Wisconsin, Milwaukee, and colleagues completed a retrospective chart review of 550 dermatology patients at Children’s Wisconsin, also in Milwaukee, who completed at least 2 months of isotretinoin treatment for acne when they were between the ages of 10 and 24, from November 2012 to January 2020. They collected data on age, weight, height, daily dose, cumulative dose, time to acne clearance, side effects, and acne recurrence after treatment, and classified patients as normal weight, overweight, or obese based on their body mass index for age percentile.
Of the 550 patients, 367 (67%) were normal weight, 101 (18%) were overweight, and 82 (15%) were obese. The median age of those in the normal-weight and overweight groups was 16, and was 15 in the obese group.
There was were significant differences in the median cumulative dose in each weight group: 143.7 mg/kg for normal-weight patients, 138.2 mg/kg for overweight patients, and 140.6 mg/kg for obese patients (P < .001).
“Despite achieving different cumulative doses, there was no difference in acne clearance, relapse, and most side effects among the three [body mass index] cohorts,” Ms. Tallmadge said. “Thus, it appears that current treatment strategies may be appropriate for overweight and obese adolescents.”
The proportion of patients with acne clearance did not differ significantly among the three groups of patients: 62% who were in the normal weight range, 60% who were overweight, and 59% who were obese had clearance of facial acne with treatment (P = .84).
Of patients whose treatment course was completed by the time of data collection, the proportion with acne recurrences was similar between the three groups: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients (P > .05). Of patients whose treatment course was completed by the time of data collection, there was no significant differences in acne recurrence: 25% of normal-weight patients, 27% of overweight patients, and 35% of obese patients.
However, the proportion of patients reporting headaches differed significantly between the groups: 29% of normal-weight patients, compared with 40% of both overweight and obese patients (P = .035). The researchers also observed a significant positive correlation between increased BMI and increased triglyceride and ALT levels during treatment (P < .001 for both associations), yet no elevations required clinical action.
Funding for the study was provided by the MCW Medical Student Summer Research Program and the American Acne & Rosacea Society.
FROM SPD 2021
Sublingual immunotherapy: Where does it stand?
Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.
Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”
SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
Why hasn’t food allergy SLIT caught on?
One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.
Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.
The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.
Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).
Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.
With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”
Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.
Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.
However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”
In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.
There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”
Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.
Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.
Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.
Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.
The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.
Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.
Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.
Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”
The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”
A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.
Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.
Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”
SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
Why hasn’t food allergy SLIT caught on?
One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.
Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.
The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.
Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).
Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.
With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”
Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.
Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.
However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”
In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.
There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”
Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.
Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.
Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.
Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.
The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.
Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.
Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.
Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”
The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”
A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.
Sublingual immunotherapy (SLIT) emerged over a century ago as a gentler alternative to allergy shots. It uses the same antigens found in allergy shots, delivering them through tablets or drops under the tongue rather than by injecting them into the skin.
Yet injection immunotherapy has been the mainstay of allergy treatment in the United States. Allergy shots are “the bread and butter, keeping the lights on at allergy practices,” said allergist Sakina Bajowala, MD, of Kaneland Allergy and Asthma Center, in the Chicago area. So even “when environmental SLIT showed quite clearly that it had efficacy, people were so slow to adapt.”
SLIT – a daily treatment that builds protection from allergens gradually over years with few side effects – is popular around the globe, particularly for environmental allergies. But only a handful of clinics offer food SLIT. Even though recent trials in peanut-allergic children show that SLIT is far safer than oral immunotherapy and about as effective as the Food and Drug Administration–approved peanut-allergy product and has lasting benefits for toddlers, many allergists lack experience with customized immunotherapies and hesitate to offer an unregulated treatment for which the evidence base is still emerging.
Why hasn’t food allergy SLIT caught on?
One issue is that there is scant evidence from randomized, controlled trials. The treatments that clinics offer often hinge on insurance coverage, and increasingly, insurers only cover FDA-approved products. FDA approval requires thousands of patients being enrolled in long, expensive studies to prove the treatment’s merit. In a similar vein, doctors are trained to question methods that lack a strong publication base, for good reason.
Yet SLIT caught the attention of pioneering physicians who were intrigued by this “low-and-slow” immune-modifying approach, despite limited published evidence, and they sought real-world experience.
The late physician David Morris, MD, came across SLIT in the 1960s while searching for alternative ways to help mold-allergic farmers who were suffering terrible side effects from allergy shots. Dr. Morris attended conferences, learned more about sublingual techniques, got board certified in allergy, and opened Allergy Associates of La Crosse (Wis.), in 1970 to offer SLIT as a treatment for food and environmental allergies.
Dr. Morris and colleagues developed a protocol to create custom SLIT drops tailored to individual patients’ clinical histories and allergy test results. The method has been used to treat more than 200,000 patients. It has been used by allergist Nikhila Schroeder, MD, MEng, who learned SLIT methods while treating nearly 1,000 patients at Allergy Associates. In 2018, she opened her own direct-care SLIT practice, Allergenuity Health, in the Charlotte metropolitan area of North Carolina (see part 2 of this series).
Dr. Bajowala’s clinic offers SLIT in addition to oral immunotherapy (OIT). She was encouraged by the recent toddler SLIT data but wondered whether it would translate to a real-world setting. According to her calculations, the published protocol – according to which participants receive up to 4 mg/d over 6 months and continue receiving a daily maintenance dose of 4 mg for 3 years – would cost $10,000 per patient.
With this dosing regimen, the intervention is unaffordable, Dr. Bajowala said. And “there’s no way to make it cheaper because that’s the raw materials cost. It does not include labor or bottles or profit at all. That’s just $10,000 in peanut extract.”
Owing to cost, Dr. Bajowala’s clinic generally uses SLIT as a bridge to OIT. Her food allergy patients receive up to 1 mg/d and remain at that dose for a month or so before transitioning to OIT, “for which the supplies are orders of magnitude cheaper,” she said.
Dr. Schroeder said there is evidence for efficacy at microgram and even nanogram dosing – much lower than used in the recent food SLIT trials. Maintenance doses range from 50 ng/d to 25 mcg/d for environmental SLIT and 4-37 mcg/d for food SLIT, she said. The La Crosse method uses even lower dose ranges.
However, dosing information is not readily available, Dr. Schroeder noted. She has spent years scrutinizing articles and compiling information from allergen extract suppliers – all the while treating hundreds of SLIT patients. “I have had to expend a lot of time and effort,” said Dr. Schroeder. “It’s really hard to explain quickly.”
In the published literature, SLIT dosing recommendations vary widely. According to a 2007 analysis, environmental allergy symptoms improved with doses over a 1,000-fold range. What’s more, success did not scale with increased dosing and seemed to depend more on frequency and duration of treatment.
There are fewer studies regarding food SLIT. The most promising data come from recent trials of peanut-allergic children led by Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill. Still, “I am nervous to tell people to go do this based on 150 kids at one site,” Dr. Kim said. “We need to have a gigantic study across multiple sites that actually confirms what we have found in our single center.”
Because there are few published trials of food SLIT, confusion about which doses are optimal, how early to start, and how long the benefits last will be a barrier for many clinicians, said Douglas Mack, MD, FRCPC, assistant clinical professor in pediatrics at McMaster University, Hamilton, Ont.
Much could be learned from Allergy Associates of La Crosse, Allergenuity Health, and other clinics with SLIT experience involving thousands of patients. But that real-world data are messy and difficult to publish. Plus, it is hard for private allergists to find time to review charts, analyze data, and draft papers alongside seeing patients and running a clinic – especially without students and interns, who typically assist with academic research, Dr. Schroeder said.
Ruchi Gupta, MD, MPH, professor of pediatrics and medicine at Northwestern University, Chicago, and colleagues worked with a La Crosse team 6 or 7 years ago to try to analyze and publish SLIT outcomes for 121 peanut-allergic children who were treated for food and environmental allergies at the Wisconsin clinic. The researchers had hoped to publish an article describing caregiver-reported and clinical outcomes.
Among 73 caregivers who responded to a survey, more than half reported improved eczema, asthma, and environmental allergy symptoms, and virtually all families said SLIT calmed anxieties and minimized fear of allergic reactions. However, the clinical outcomes – skinprick test results, immune changes, and oral food challenges – were not as robust. And the data were incomplete. Some patients had traveled to La Crosse for SLIT drops but underwent skin and blood testing with their local allergist. Compiling records is “so much harder when you’re not doing a prospective clinical trial,” Dr. Gupta said.
The caregiver-reported outcomes were presented as a poster at the 2015 annual meeting of the American College of Allergy, Asthma, and Immunology and the 2016 annual meeting of the Pediatric Academic Society, said Jeff Kessler, MBA, FACHE, who is practice executive at La Crosse. However, with only self-reported data and no convincing lab metrics, the findings were never submitted for publication.
Others are eager to see clearer proof that SLIT works at doses lower than those published in the most recent trials. “If we can get efficacy with lower doses, that means we can increase accessibility, because we can lower the cost,” Dr. Bajowala said.
Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins University, Baltimore, has a pending grant proposal for a multifood trial of SLIT. “It’s a big missing piece,” he said.
Dr. Mack said that in Canada there was “almost an instant change in group think” when the Canadian Society of Allergy and Clinical Immunology published guidelines in support of OIT. With the new guidelines, “people are less concerned about liability. Once they start getting into OIT, I think you’re going to see SLIT coming right along for the ride.”
The shift will be slower in the United States, which has 20 times as many practicing allergists as Canada. Nevertheless, “I totally think SLIT has a place at the table,” Dr. Mack said. “I hope we start to see more high-quality data and people start to use it and experiment with it a bit and see how it works.”
A version of this article first appeared on Medscape.com. This is part three of a three-part series. Part one is here. Part two is here.
Direct-care allergy clinic specializes in sublingual immunotherapy
With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.
Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”
Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.
Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.
This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.
Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.
The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
Unforgettable day
Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”
All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.
Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.
During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”
Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”
Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).
The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.
Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.
Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.
Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.
Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.
Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”
Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”
Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”
A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.
With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.
Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”
Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.
Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.
This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.
Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.
The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
Unforgettable day
Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”
All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.
Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.
During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”
Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”
Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).
The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.
Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.
Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.
Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.
Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.
Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”
Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”
Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”
A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.
With degrees in electrical engineering and computer science from the Massachusetts Institute of Technology, Nikhila Schroeder, MD, MEng, brings a problem-solving mindset to medicine.
Being a doctor means having to “figure out all aspects of [a patient’s] situation and do my best to come up with an answer,” said Dr. Schroeder, who founded Allergenuity Health, a solo allergy practice in Huntersville, N.C., with her husband James, who serves as practice executive. It’s “being a medical detective for your patient.”
Yet, during her training, Dr. Schroeder found that market-driven health care makes it hard to practice medicine with a patient’s best interest foremost. Procedures for diagnosing and treating disease cater to insurance companies’ reimbursement policies. “You wind up having to tailor your care to whatever insurance will cover,” she said.
Insurers, in turn, look for evidence from large, peer-reviewed studies to prove that a treatment works. Many physicians hesitate to offer therapies that aren’t covered by insurance, for both liability and financial reasons. So treatment tends to be limited to those options that were rigorously vetted in long, costly, multisite trials that are difficult to conduct without a corporate sponsor.
This is why there is still only one licensed treatment for people with food allergies – a set of standardized peanut powder capsules (Palforzia) that was approved by the Food and Drug Administration in early 2020 for peanut-allergic children aged 4-17 years. A small but growing number of allergists offer unapproved oral immunotherapy (OIT) using commercial food products to treat allergies to peanuts and other foods.
Even fewer allergists treat food allergy patients with another immune-modifying treatment, sublingual immunotherapy (SLIT), which delivers allergens through liquid drops held for several minutes under the tongue. Since 2018, Allergenuity Health, which offers SLIT to treat food and environmental allergies, has provided care to more than 400 patients. More than a third have come from out of state.
The clinic uses a direct-care approach. Rather than taking insurance, the clinic offers a monthly billing program that includes tests, SLIT bottles, and access to Dr. Schroeder via phone, email, or text. “I’m only contracted with the patient, and my only focus is the patient,” Dr. Schroeder said in an interview.
Unforgettable day
Allergy was not on Dr. Schroeder’s radar in medical school. She wanted to be a surgeon. But she loved working with children, so she did a pediatrics residency at the University of Virginia Children’s Hospital in Charlottesville. There Dr. Schroeder started seeing kids with eczema and allergies. While covering a friend’s clinic shift in 2010, she was thrust into an emergency. A family who didn’t speak English had just brought in their screaming 6-month-old baby, red and puffy with hives. “We didn’t know what was going on with this child,” Dr. Schroeder said. “Somehow I was elected to go in there.”
All of a sudden, things got quiet. Yet the baby was still screaming, mouth wide open. Dr. Schroeder had learned about anaphylaxis but had never witnessed it – until that day. The baby›s airways swelled so much that the crying became hoarse and soft. After working with a nurse to administer epinephrine, Dr. Schroeder saw something equally unforgettable: The baby’s heart rate soared, but within minutes the hives and swelling subsided and smiles returned. “It was incredible how quickly things changed,” Dr. Schroeder said. The baby had a reaction to rice, an uncommon allergen.
Dr. Schroeder stayed at UVA 2 more years to complete an allergy and immunology fellowship. She learned to diagnose food allergies but became frustrated having to tell patients they had little recourse but to avoid the food and to check in every year or 2. “I was, like, aren’t we specialists? Shouldn’t we have a little more expertise and maybe see if there are ways we could change this?” Dr. Schroeder said.
During those years, allergy shots were the only form of immunotherapy being taught to fellows. At clinic, Dr. Schroeder served as backup to the nurses when someone reacted to shots. She was troubled that some patients needed epinephrine to stop asthma attacks caused by injections they had received as treatment. The idea of injecting substances under the skin seemed akin to vaccination – where “you want to aggravate the immune system, you want it to get revved up, you want to build it up to fight,” she said. “But that’s not what you want for allergy. You want to tone it down. It didn’t really, to be honest, make a lot of sense to me.”
Dr. Schroeder started digging and asking questions. How does the immune system decide what is safe? Which cells and molecules communicate these decisions? She thought about babies and how they “learn” by putting stuff into their mouths. “If we don’t tolerate most of what we take in there, we wouldn’t survive,” Dr. Schroeder said. “It makes a lot of sense that a lot of tolerance begins with cells of the mouth.”
Dr. Schroeder discussed these concepts with her attendings. “They were all, like, no, there’s really no good evidence for that,” she said. But at some point, someone mentioned sublingual immunotherapy, and Schroeder came across Allergy Associates of La Crosse (Wis.).
The clinic’s late founder, David Morris, MD, learned about SLIT in the 1960s as an alternative option for farmers who suffered terrible side effects from injection immunotherapy they received to treat their mold allergies. Dr. Morris attended conferences, learned more about sublingual techniques – at times seeking advice from European allergists who offered SLIT – and became board certified in allergy before opening the La Crosse clinic in 1970. According to the clinic, more than 200,000 patients with environmental and food allergies have been treated with its SLIT protocol.
Dr. Schroeder was shocked to discover that this clinic had existed for 40 years, yet “I, as an allergist, had heard nothing about them,” she said.
Toward the end of her fellowship, OIT was becoming more well known. But she felt its risks were often downplayed. After years of talking with food allergy patients, Schroeder realized that most didn’t actually care about eating peanut butter sandwiches or sesame or walnuts. “Often I would hear, through tears: ‘I just want my child to be able to sit with their friends at lunch, to not be put at this other table, to not feel so isolated,’ ” she said. What mattered most to many families was gaining enough protection to not feel anxious about participating in social activities involving food.
Dr. Schroeder had a growing sense that SLIT – given its ease, safety, and sensible route of allergen delivery – seemed more useful. She wanted to learn more.
Her mentors urged her to stay in academia instead. “They were, like, you have a good academic reputation. You’re a solid thinker. You’re great at what you do. Do the traditional stuff,” Dr. Schroeder said.
Despite these admonitions, Dr. Schroeder left academia and took a job at La Crosse after completing her allergy fellowship. Determined to see whether SLIT could be effective, “I decided in the end, you know what, I have to go do this,” she said. “I need to know, and the only way I’m going to know is to do it, because no one was giving me good information.”
Before treating anyone with SLIT, Dr. Schroeder tried it herself – as a La Crosse patient. Growing up with severe eczema, eye swelling, and chronic nasal congestion leading to sinus infections, “I myself was a severely allergic person,” she said. Within several months, Dr. Schroeder saw dramatic improvement in her symptoms – “a night and day difference.” She experienced some mouth tingling, one of SLIT’s most common side effects, but found it “very tolerable, very mild.”
Allergenuity Health doesn’t aim to promote SLIT as the best treatment, said Dr. Schroeder, who has helped some families use avoidance or OIT as a better option. “An initial evaluation is always about proper diagnosis and education about all the treatment options available. Really, the point is education – be a detective for them and figure out what’s going on, be honest about what we know and what we don’t know, and give them the tools to figure out how to proceed.”
A version of this article first appeared on Medscape.com. This is part two of a three-part series. Part one is here. Part three is here.
There’s a much safer food allergy immunotherapy – why don’t more doctors offer it?
For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.
A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.
An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.
Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”
Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.
Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
Concerns about SLIT
One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.
On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.
But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).
Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.
Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”
Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.
But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.
Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”
On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”
Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.
SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.
As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.
One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.
A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.
For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.
A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.
An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.
Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”
Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.
Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
Concerns about SLIT
One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.
On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.
But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).
Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.
Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”
Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.
But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.
Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”
On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”
Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.
SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.
As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.
One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.
A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.
For the 32 million people in the United States with food allergies, those who seek relief beyond constant vigilance and EpiPens face a confusing treatment landscape. In January 2020, the Food and Drug Administration approved an oral immunotherapy product (Palforzia) for peanut-allergic children. Yet the product’s ill-timed release during a pandemic and its black-box warning about the risk for anaphylaxis has slowed uptake.
A small number of allergists offer home-grown oral immunotherapy (OIT), which builds protection by exposing patients to increasing daily doses of commercial food products over months. However, as with Palforzia, allergic reactions are common during treatment, and the hard-earned protection can fade if not maintained with regular dosing.
An alternate approach, sublingual immunotherapy (SLIT), delivers food proteins through liquid drops held in the mouth – a site rich in tolerance-inducing immune cells. In a 2019 study of peanut-allergic children aged 1-11 years, SLIT offered a level of protection on par with Palforzia while causing considerably fewer adverse events. And at the 2021 annual meeting of the American Academy of Allergy, Asthma and Immunology, researchers reported that SLIT produced stronger, more durable benefits in toddlers aged 1-4.
Sublingual immunotherapy is “a bunch of drops you put under your tongue, you hold it for a couple minutes, and then you’re done for the day,” said Edwin Kim, MD, director of the UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, who led the two recent studies. For protecting against accidental ingestions, SLIT “is pushing pretty close to what OIT is able to provide but seemingly with a superior ease of administration and safety profile.”
Many parents don’t necessarily want their allergic kids to be able to eat a peanut butter sandwich – but do want them to be able to safely sit at the same lunch table and attend birthday parties with other kids. SLIT achieves this level of protection about as well as OIT, with fewer side effects.
Still, because of concerns about the treatment’s cost, unclear dosing regimens, and lack of FDA approval, very few U.S. allergists – likely less than 5% – offer sublingual immunotherapy to treat food allergies, making SLIT even less available than OIT.
Concerns about SLIT
One possible reason: Success is slower and less visible for SLIT. When patients undergo OIT, they build up to dosing with the actual food. “To a family who has a concern about their kid reacting, they can see them eating chunks of peanut in our office. That is really encouraging,” said Douglas Mack, MD, FRCPC, an allergist with Halton Pediatric Allergy and assistant clinical professor of pediatrics at McMaster University, Hamilton, Ont.
On the other hand, ingestion isn’t the focus for SLIT, so progress is harder to measure using metrics in published trials. After holding SLIT drops under the tongue, some patients spit them out. If they swallow the dose, it’s a vanishingly small amount. Immune changes that reflect increasing tolerance, such as a decrease in IgE antibodies, tend to be more gradual with SLIT than with OIT. And because SLIT is only offered in private clinics, such tests are not conducted as regularly as they would be for published trials.
But there may be a bigger factor: Some think earlier trials comparing the two immunotherapy regimens gave SLIT a bad rap. For example, in studies of milk- and peanut-allergic children conducted in 2011 and 2014, investigators concluded that SLIT was safer and that OIT appeared to be more effective. However, those trials compared SLIT with OIT using a much higher dose (2,000 mg) than is used in the licensed product (300 mg).
Over the years, endpoints for food allergy treatment trials have shifted from enabling patients to eat a full serving of their allergen to merely raising their threshold to guard against accidental exposures. So in those earlier articles, “we would probably write the discussion section differently now,” said Corinne Keet, MD, PhD, first author on the 2011 milk study and an associate professor of pediatrics at Johns Hopkins University, Baltimore.
Indeed, “when you compare [SLIT] to Palforzia or other studies of low-dose OIT (300 mg/d), they look equal in terms of their efficacy,” said senior author Robert Wood, MD, professor of pediatrics and director of pediatric allergy and immunology at Johns Hopkins. Yet, “I’m afraid we had a major [negative] impact on pharma’s interest in pursuing SLIT.”
Without corporate funding, it’s nearly impossible to conduct the large, multisite trials required for FDA approval of a treatment. And without approved products, many allergists are reluctant to offer the therapy, Dr. Wood said. It “makes your life a lot more complicated to be dabbling in things that are not approved,” he noted.
But at least one company is giving it a go. Applying the SLIT principle of delivering food allergens to tolerance-promoting immune cells in the mouth, New York–based Intrommune Therapeutics recently started enrolling peanut-allergic adults for a phase 1 trial of its experimental toothpaste.
Interest in food-allergy SLIT seems to be growing. “I definitely think that it could be an option for the future,” said Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic. “Up until a few months ago, it really wasn’t on our radar.”
On conversations with Dr. Kim, philanthropists and drug developers said they found the recent data on SLIT promising, yet pointed out that food SLIT protocols and products are already in the public domain – they are described in published research using allergen extracts that are on the market. They “can’t see a commercial path forward,” Dr. Kim said in an interview. “And that’s kind of where many of my conversations end.”
Although there are no licensed SLIT products for food allergies, between 2014 and 2017, the FDA approved four sublingual immunotherapy tablets to treat environmental allergies – Stallergenes-Greer’s Oralair and ALK’s Grastek for grass pollens, ALK’s Odactra for dust mites, and ALK’s Ragwitek for short ragweed.
SLIT tablets work as well as allergy shots (subcutaneous immunotherapy) for controlling environmental allergy symptoms, they have a better safety profile, according to AAAAI guidelines, and they can be self-administered at home, which has made them a popular option globally. “Our European colleagues have used sublingual immunotherapy much more frequently than, for example, in the U.S.,” said Kari Nadeau, MD, PhD, director of the Sean N. Parker Center for Allergy and Asthma Research at Stanford (Calif.) University.
Use of SLIT is also increasing in the United States, especially as FDA-approved products become available. In a 2019 survey, the percentage of U.S. allergists who said they were offering sublingual treatment for environmental allergies increased from 5.9% in 2007 to 73.5% in 2019. However, only 11.2% reported extensive SLIT use; the remainder reported some (50.5%) or little (38.3%) use.
As noted above, considerably fewer U.S. allergists use SLIT to treat food allergies. Similarly, a 2021 survey of allergists in Canada found that only 7% offered food sublingual immunotherapy; more than half reported offering OIT.
One practice, Allergy Associates of La Crosse (Wis.), has offered SLIT drops for food and environmental allergies for decades. Since the clinic opened in 1970, more than 200,000 people have been treated with its protocol. Every patient receives customized sublingual drops – “exactly what they’re allergic to, exactly how allergic they are, and then we build from there,” said Jeff Kessler, MBA, FACHE, practice executive at Allergy Associates of La Crosse. “Quite frankly, it’s the way immunotherapy should be done.
A version of this article first appeared on Medscape.com. This is part one of a three-part series. Part two is here. Part three is here.
The case for suicide-risk screening in primary care
Suicide-risk screening may identify cases that typically fall through the cracks during depression screening, new research suggests.
The study, published in Pediatrics, found that the Ask Suicide-Screening Questions (ASQ) identified 2.2% of additional cases compared with those screened for any type of depression or other mental illnesses, and 8.3% of additional cases compared with those who screened positive for major depressive disorder.
About 3.2% of U.S. children between the ages of 3 and 17 have been diagnosed with depression, according to the Centers for Disease Control and Prevention. The American Academy of Pediatrics and the U.S. Preventive Services Task Force recommends that all teens be routinely screened for depression. However, there’s no specific recommendation that adolescents should also be screened for suicide in addition to depression screening.
The study highlights the high baseline rates of depression and suicide risk and the need for pediatric practices to plan for them and develop strategies about how they’re going to provide follow-up care, including treatment for suicidal teens.
“We began this project because we were concerned that we might be missing teens with increased risk of suicide by screening only for depression,” study author Alex Kemper, MD, said in an interview. “Our goal with this project was really to compare standard depression screening tools that we’ve used for a long time with a suicide-specific instrument just to see if we would identify additional cases with a suicide-risk instrument.”
Dr. Kemper and colleagues collected data from 803 mostly Medicaid-enrolled adolescents across 12 primary care practices. The subjects were between the ages of 12 and 20 years, with no recent history of depression or self-harm, who were screened with the Patient Health Questionnaire–9 Modified for Adolescents (PHQ-9A) and ASQ. For the study, two PHQ-9A screening strategies were evaluated: screening for any type of depression or other mental illness (positive on any item) or screening for major depressive disorder.
In addition, the researchers found that 56.4% of patients had a positive PHQ-9A screen for any type of depression and 24.7% had a positive PHQ-9A screen for major depressive disorder. Meanwhile, 21.1% of the population received a positive screen result. Of those who responded on the PHQ-9A that they did not have suicidal thoughts in the past month, 13.2% had a positive ASQ result.
Dr. Kemper, division chief of primary care pediatrics at Nationwide Children’s Hospital and professor of pediatrics at the Ohio State University, both in Columbus, said the suicide-risk screening questions were more direct and clear than were the two suicide questions included in the PHQ-9A screening.
For example, the PHQ-9A includes the following suicide-risk questions: “Has there been a time in the past month when you have had serious thoughts about ending your life?” and “Have you EVER, in your WHOLE LIFE, tried to kill yourself or made a suicide attempt?” The teen can respond with “not at all,” “several days,” “more than half the days” or “nearly every day.”
Meanwhile, the ASQ questionnaire focuses on a more narrow time period and includes questions such as “In the past few weeks, have you wished you were dead?” and “Have you ever tried to kill yourself?” Teens respond by answering “yes” or “no.”
“So I think the difference is by asking questions that are really direct and very clear about suicide risk, you end up identifying more cases than this kind of general question about thoughts of killing yourself,” Dr. Kemper explained. “It makes sense when you think about where adolescents are in terms of their development, that the more specific you [are], the more likely you are to find what you’re looking for.”
Kelly Curran, MD, who was not involved in the study, said that because some of the ASQ questions “overlap” with the suicide-risk questions on the PHQ-9A, she didn’t expect the ASQ to identify more positive cases.
However, Dr. Curran said it is possible for suicidal teens to fall through the cracks during a depression screening because some of them may not self-identify as depressed.
“I don’t think we often think about the importance of linguistics or how something is asked,” said Dr. Curran, associate professor in the department of pediatrics at the University of Oklahoma, Oklahoma City.
“So asking [teens] these kind of direct questions about suicide may pick up on these cases of people who don’t necessarily have the insight into their sadness or their general kind of thought process.”
Dr. Kemper said he hopes the study would encourage pediatricians to adopt depression screening if they’re not already doing it and to think about whether they should implement suicide-risk screening in their practice. The study also highlights the importance of following up after a positive screening.
“There are a lot of teens who have depression or increased suicide risk that you wouldn’t identify if you didn’t screen, and a key aspect of any kind of screening is that you need to be prepared to provide follow-up care after a positive screening,” he explained.
Study limitations include the fact that the subjects were recruited from a single health care system that serves mostly urban and low-income communities, and that the study was not designed to determine test accuracy.
Dr. Kemper and Dr. Curran indicated that they have no financial disclosures.
Suicide-risk screening may identify cases that typically fall through the cracks during depression screening, new research suggests.
The study, published in Pediatrics, found that the Ask Suicide-Screening Questions (ASQ) identified 2.2% of additional cases compared with those screened for any type of depression or other mental illnesses, and 8.3% of additional cases compared with those who screened positive for major depressive disorder.
About 3.2% of U.S. children between the ages of 3 and 17 have been diagnosed with depression, according to the Centers for Disease Control and Prevention. The American Academy of Pediatrics and the U.S. Preventive Services Task Force recommends that all teens be routinely screened for depression. However, there’s no specific recommendation that adolescents should also be screened for suicide in addition to depression screening.
The study highlights the high baseline rates of depression and suicide risk and the need for pediatric practices to plan for them and develop strategies about how they’re going to provide follow-up care, including treatment for suicidal teens.
“We began this project because we were concerned that we might be missing teens with increased risk of suicide by screening only for depression,” study author Alex Kemper, MD, said in an interview. “Our goal with this project was really to compare standard depression screening tools that we’ve used for a long time with a suicide-specific instrument just to see if we would identify additional cases with a suicide-risk instrument.”
Dr. Kemper and colleagues collected data from 803 mostly Medicaid-enrolled adolescents across 12 primary care practices. The subjects were between the ages of 12 and 20 years, with no recent history of depression or self-harm, who were screened with the Patient Health Questionnaire–9 Modified for Adolescents (PHQ-9A) and ASQ. For the study, two PHQ-9A screening strategies were evaluated: screening for any type of depression or other mental illness (positive on any item) or screening for major depressive disorder.
In addition, the researchers found that 56.4% of patients had a positive PHQ-9A screen for any type of depression and 24.7% had a positive PHQ-9A screen for major depressive disorder. Meanwhile, 21.1% of the population received a positive screen result. Of those who responded on the PHQ-9A that they did not have suicidal thoughts in the past month, 13.2% had a positive ASQ result.
Dr. Kemper, division chief of primary care pediatrics at Nationwide Children’s Hospital and professor of pediatrics at the Ohio State University, both in Columbus, said the suicide-risk screening questions were more direct and clear than were the two suicide questions included in the PHQ-9A screening.
For example, the PHQ-9A includes the following suicide-risk questions: “Has there been a time in the past month when you have had serious thoughts about ending your life?” and “Have you EVER, in your WHOLE LIFE, tried to kill yourself or made a suicide attempt?” The teen can respond with “not at all,” “several days,” “more than half the days” or “nearly every day.”
Meanwhile, the ASQ questionnaire focuses on a more narrow time period and includes questions such as “In the past few weeks, have you wished you were dead?” and “Have you ever tried to kill yourself?” Teens respond by answering “yes” or “no.”
“So I think the difference is by asking questions that are really direct and very clear about suicide risk, you end up identifying more cases than this kind of general question about thoughts of killing yourself,” Dr. Kemper explained. “It makes sense when you think about where adolescents are in terms of their development, that the more specific you [are], the more likely you are to find what you’re looking for.”
Kelly Curran, MD, who was not involved in the study, said that because some of the ASQ questions “overlap” with the suicide-risk questions on the PHQ-9A, she didn’t expect the ASQ to identify more positive cases.
However, Dr. Curran said it is possible for suicidal teens to fall through the cracks during a depression screening because some of them may not self-identify as depressed.
“I don’t think we often think about the importance of linguistics or how something is asked,” said Dr. Curran, associate professor in the department of pediatrics at the University of Oklahoma, Oklahoma City.
“So asking [teens] these kind of direct questions about suicide may pick up on these cases of people who don’t necessarily have the insight into their sadness or their general kind of thought process.”
Dr. Kemper said he hopes the study would encourage pediatricians to adopt depression screening if they’re not already doing it and to think about whether they should implement suicide-risk screening in their practice. The study also highlights the importance of following up after a positive screening.
“There are a lot of teens who have depression or increased suicide risk that you wouldn’t identify if you didn’t screen, and a key aspect of any kind of screening is that you need to be prepared to provide follow-up care after a positive screening,” he explained.
Study limitations include the fact that the subjects were recruited from a single health care system that serves mostly urban and low-income communities, and that the study was not designed to determine test accuracy.
Dr. Kemper and Dr. Curran indicated that they have no financial disclosures.
Suicide-risk screening may identify cases that typically fall through the cracks during depression screening, new research suggests.
The study, published in Pediatrics, found that the Ask Suicide-Screening Questions (ASQ) identified 2.2% of additional cases compared with those screened for any type of depression or other mental illnesses, and 8.3% of additional cases compared with those who screened positive for major depressive disorder.
About 3.2% of U.S. children between the ages of 3 and 17 have been diagnosed with depression, according to the Centers for Disease Control and Prevention. The American Academy of Pediatrics and the U.S. Preventive Services Task Force recommends that all teens be routinely screened for depression. However, there’s no specific recommendation that adolescents should also be screened for suicide in addition to depression screening.
The study highlights the high baseline rates of depression and suicide risk and the need for pediatric practices to plan for them and develop strategies about how they’re going to provide follow-up care, including treatment for suicidal teens.
“We began this project because we were concerned that we might be missing teens with increased risk of suicide by screening only for depression,” study author Alex Kemper, MD, said in an interview. “Our goal with this project was really to compare standard depression screening tools that we’ve used for a long time with a suicide-specific instrument just to see if we would identify additional cases with a suicide-risk instrument.”
Dr. Kemper and colleagues collected data from 803 mostly Medicaid-enrolled adolescents across 12 primary care practices. The subjects were between the ages of 12 and 20 years, with no recent history of depression or self-harm, who were screened with the Patient Health Questionnaire–9 Modified for Adolescents (PHQ-9A) and ASQ. For the study, two PHQ-9A screening strategies were evaluated: screening for any type of depression or other mental illness (positive on any item) or screening for major depressive disorder.
In addition, the researchers found that 56.4% of patients had a positive PHQ-9A screen for any type of depression and 24.7% had a positive PHQ-9A screen for major depressive disorder. Meanwhile, 21.1% of the population received a positive screen result. Of those who responded on the PHQ-9A that they did not have suicidal thoughts in the past month, 13.2% had a positive ASQ result.
Dr. Kemper, division chief of primary care pediatrics at Nationwide Children’s Hospital and professor of pediatrics at the Ohio State University, both in Columbus, said the suicide-risk screening questions were more direct and clear than were the two suicide questions included in the PHQ-9A screening.
For example, the PHQ-9A includes the following suicide-risk questions: “Has there been a time in the past month when you have had serious thoughts about ending your life?” and “Have you EVER, in your WHOLE LIFE, tried to kill yourself or made a suicide attempt?” The teen can respond with “not at all,” “several days,” “more than half the days” or “nearly every day.”
Meanwhile, the ASQ questionnaire focuses on a more narrow time period and includes questions such as “In the past few weeks, have you wished you were dead?” and “Have you ever tried to kill yourself?” Teens respond by answering “yes” or “no.”
“So I think the difference is by asking questions that are really direct and very clear about suicide risk, you end up identifying more cases than this kind of general question about thoughts of killing yourself,” Dr. Kemper explained. “It makes sense when you think about where adolescents are in terms of their development, that the more specific you [are], the more likely you are to find what you’re looking for.”
Kelly Curran, MD, who was not involved in the study, said that because some of the ASQ questions “overlap” with the suicide-risk questions on the PHQ-9A, she didn’t expect the ASQ to identify more positive cases.
However, Dr. Curran said it is possible for suicidal teens to fall through the cracks during a depression screening because some of them may not self-identify as depressed.
“I don’t think we often think about the importance of linguistics or how something is asked,” said Dr. Curran, associate professor in the department of pediatrics at the University of Oklahoma, Oklahoma City.
“So asking [teens] these kind of direct questions about suicide may pick up on these cases of people who don’t necessarily have the insight into their sadness or their general kind of thought process.”
Dr. Kemper said he hopes the study would encourage pediatricians to adopt depression screening if they’re not already doing it and to think about whether they should implement suicide-risk screening in their practice. The study also highlights the importance of following up after a positive screening.
“There are a lot of teens who have depression or increased suicide risk that you wouldn’t identify if you didn’t screen, and a key aspect of any kind of screening is that you need to be prepared to provide follow-up care after a positive screening,” he explained.
Study limitations include the fact that the subjects were recruited from a single health care system that serves mostly urban and low-income communities, and that the study was not designed to determine test accuracy.
Dr. Kemper and Dr. Curran indicated that they have no financial disclosures.
Study spanning 2 decades offers insights into pediatric psoriasis trends
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.
Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.
“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”
To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.
Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).
Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).
Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.
The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.
Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”
Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).
“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”
In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.
“Though methodologies and patient populations differ among studies, what is striking,” she said, is the percentage of overweight/obese patients (37%; defined as a body mass index ≥ 85th percentile) “in our 2-decade single institution dataset.” This “is nearly identical” to the percentage of patients with excess adiposity – 37.9% (also defined as BMI ≥ 85th percentile) – in an international cross-sectional study, which also identified an association between obesity (BMI ≥ 95th percentile) and psoriasis severity in children, she noted.
“What is clear is the strong association between obesity and childhood psoriasis, as multiple studies, including ours, confirm obesity as a major comorbidity of pediatric psoriasis,” Dr. Cordoro said. “Both conditions must be adequately managed to reduce the risk of adverse health outcomes for obese patients with psoriasis.”
The other study coauthors were Dana Feigenbaum, MD, and Alana Ju, MD. The work was supported by the UCSF Yearlong Inquiry Program. The researchers reported having no relevant financial disclosures.
FROM SPD 2021
Reassuring rates of ADHD after assisted reproductive techniques
according to a study published in Pediatrics.
The findings, based on an analysis of data from more than 1.5 million children in Sweden, provide “additional reassurance concerning offspring neurodevelopment after use of ART,” study author Chen Wang, MPH, and colleagues said. The results show the importance of accounting for underlying infertility when studying ART safety, they added. Mr. Wang is a researcher in the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
Prior research has not shown major differences during early childhood between children conceived with ART and those conceived spontaneously. To examine long-term neurodevelopmental outcomes, including ADHD and school performance, the investigators analyzed data in Swedish population registers from children born between 1986 and 2012.
Infertility and the use of ART became increasingly common during the study period, the researchers noted. Between 1986 and 2001, 7% of births were to couples with known infertility, and 13% of these births were achieved with ART. Between 1996 and 2012, 11% of births were to couples with infertility, and 26% of these births were achieved with ART.
“Couples with infertility were more likely older and married or cohabiting, compared with couples with no known infertility,” Mr. Wang and colleagues reported. “Among infertile couples, those that conceived with ART had, on average, higher age and education, and the women were less likely to smoke.”
The investigators estimated that the cumulative incidence of ADHD by age 15 years was 6.2% in children conceived with ART, 7.3% among children of couples with infertility who did not use ART, and 7.1% in children born to couples with no known infertility.
Overall, children conceived with ART were at lower risk of ADHD (hazard ratio, 0.83). But after adjusting for parental characteristics and health factors, the researchers found a “slightly elevated risk of ADHD with ART,” with adjusted HRs of 1.05-1.07.
When the researchers focused on children born to couples with infertility, ART was associated with a lower risk of ADHD (adjusted HR, 0.80), compared with spontaneous conception. Accounting for parental characteristics and health history, however, “attenuated the association toward the null,” the researchers reported.
The researchers also compared ART methods, including intracytoplasmic sperm injection versus standard in vitro fertilization (IVF), and fresh embryo transfer versus frozen embryo transfer. The various procedures were not associated with substantially different risks.
Patterns for school performance were generally similar to those for ADHD.
“In this large follow-up of nationwide birth cohorts, we observed lower risk of ADHD and slightly better overall school performance in children conceived with ART, compared with all other children. Differences in parental characteristics appeared to completely explain and even slightly reverse the associations,” the study authors said. “When the comparison was restricted to children of couples with known infertility, no differences were seen.”
The study was well designed and “spans more than 25 years of ART during which treatments have changed dramatically,” commented Barbara Luke, ScD, MPH, professor of obstetrics, gynecology, and reproductive biology at Michigan State University, East Lansing.
Dr. Luke and colleagues have studied academic achievement in children conceived with IVF in Texas. The results of the Swedish study “are in line with U.S. studies, and are generally reassuring,” Dr. Luke said.
The U.S. studies also showed that parental factors may play a role in understanding academic performance.
“In our studies of third-grade and sixth-grade academic outcomes, we found differences by racial/Hispanic origin groups, gender, and maternal age,” she said.
The study by Mr. Wang and coauthors was funded by grants from a Swedish government agency and the National Institutes of Health. The researchers and Dr. Luke had no relevant financial disclosures.
according to a study published in Pediatrics.
The findings, based on an analysis of data from more than 1.5 million children in Sweden, provide “additional reassurance concerning offspring neurodevelopment after use of ART,” study author Chen Wang, MPH, and colleagues said. The results show the importance of accounting for underlying infertility when studying ART safety, they added. Mr. Wang is a researcher in the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
Prior research has not shown major differences during early childhood between children conceived with ART and those conceived spontaneously. To examine long-term neurodevelopmental outcomes, including ADHD and school performance, the investigators analyzed data in Swedish population registers from children born between 1986 and 2012.
Infertility and the use of ART became increasingly common during the study period, the researchers noted. Between 1986 and 2001, 7% of births were to couples with known infertility, and 13% of these births were achieved with ART. Between 1996 and 2012, 11% of births were to couples with infertility, and 26% of these births were achieved with ART.
“Couples with infertility were more likely older and married or cohabiting, compared with couples with no known infertility,” Mr. Wang and colleagues reported. “Among infertile couples, those that conceived with ART had, on average, higher age and education, and the women were less likely to smoke.”
The investigators estimated that the cumulative incidence of ADHD by age 15 years was 6.2% in children conceived with ART, 7.3% among children of couples with infertility who did not use ART, and 7.1% in children born to couples with no known infertility.
Overall, children conceived with ART were at lower risk of ADHD (hazard ratio, 0.83). But after adjusting for parental characteristics and health factors, the researchers found a “slightly elevated risk of ADHD with ART,” with adjusted HRs of 1.05-1.07.
When the researchers focused on children born to couples with infertility, ART was associated with a lower risk of ADHD (adjusted HR, 0.80), compared with spontaneous conception. Accounting for parental characteristics and health history, however, “attenuated the association toward the null,” the researchers reported.
The researchers also compared ART methods, including intracytoplasmic sperm injection versus standard in vitro fertilization (IVF), and fresh embryo transfer versus frozen embryo transfer. The various procedures were not associated with substantially different risks.
Patterns for school performance were generally similar to those for ADHD.
“In this large follow-up of nationwide birth cohorts, we observed lower risk of ADHD and slightly better overall school performance in children conceived with ART, compared with all other children. Differences in parental characteristics appeared to completely explain and even slightly reverse the associations,” the study authors said. “When the comparison was restricted to children of couples with known infertility, no differences were seen.”
The study was well designed and “spans more than 25 years of ART during which treatments have changed dramatically,” commented Barbara Luke, ScD, MPH, professor of obstetrics, gynecology, and reproductive biology at Michigan State University, East Lansing.
Dr. Luke and colleagues have studied academic achievement in children conceived with IVF in Texas. The results of the Swedish study “are in line with U.S. studies, and are generally reassuring,” Dr. Luke said.
The U.S. studies also showed that parental factors may play a role in understanding academic performance.
“In our studies of third-grade and sixth-grade academic outcomes, we found differences by racial/Hispanic origin groups, gender, and maternal age,” she said.
The study by Mr. Wang and coauthors was funded by grants from a Swedish government agency and the National Institutes of Health. The researchers and Dr. Luke had no relevant financial disclosures.
according to a study published in Pediatrics.
The findings, based on an analysis of data from more than 1.5 million children in Sweden, provide “additional reassurance concerning offspring neurodevelopment after use of ART,” study author Chen Wang, MPH, and colleagues said. The results show the importance of accounting for underlying infertility when studying ART safety, they added. Mr. Wang is a researcher in the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm.
Prior research has not shown major differences during early childhood between children conceived with ART and those conceived spontaneously. To examine long-term neurodevelopmental outcomes, including ADHD and school performance, the investigators analyzed data in Swedish population registers from children born between 1986 and 2012.
Infertility and the use of ART became increasingly common during the study period, the researchers noted. Between 1986 and 2001, 7% of births were to couples with known infertility, and 13% of these births were achieved with ART. Between 1996 and 2012, 11% of births were to couples with infertility, and 26% of these births were achieved with ART.
“Couples with infertility were more likely older and married or cohabiting, compared with couples with no known infertility,” Mr. Wang and colleagues reported. “Among infertile couples, those that conceived with ART had, on average, higher age and education, and the women were less likely to smoke.”
The investigators estimated that the cumulative incidence of ADHD by age 15 years was 6.2% in children conceived with ART, 7.3% among children of couples with infertility who did not use ART, and 7.1% in children born to couples with no known infertility.
Overall, children conceived with ART were at lower risk of ADHD (hazard ratio, 0.83). But after adjusting for parental characteristics and health factors, the researchers found a “slightly elevated risk of ADHD with ART,” with adjusted HRs of 1.05-1.07.
When the researchers focused on children born to couples with infertility, ART was associated with a lower risk of ADHD (adjusted HR, 0.80), compared with spontaneous conception. Accounting for parental characteristics and health history, however, “attenuated the association toward the null,” the researchers reported.
The researchers also compared ART methods, including intracytoplasmic sperm injection versus standard in vitro fertilization (IVF), and fresh embryo transfer versus frozen embryo transfer. The various procedures were not associated with substantially different risks.
Patterns for school performance were generally similar to those for ADHD.
“In this large follow-up of nationwide birth cohorts, we observed lower risk of ADHD and slightly better overall school performance in children conceived with ART, compared with all other children. Differences in parental characteristics appeared to completely explain and even slightly reverse the associations,” the study authors said. “When the comparison was restricted to children of couples with known infertility, no differences were seen.”
The study was well designed and “spans more than 25 years of ART during which treatments have changed dramatically,” commented Barbara Luke, ScD, MPH, professor of obstetrics, gynecology, and reproductive biology at Michigan State University, East Lansing.
Dr. Luke and colleagues have studied academic achievement in children conceived with IVF in Texas. The results of the Swedish study “are in line with U.S. studies, and are generally reassuring,” Dr. Luke said.
The U.S. studies also showed that parental factors may play a role in understanding academic performance.
“In our studies of third-grade and sixth-grade academic outcomes, we found differences by racial/Hispanic origin groups, gender, and maternal age,” she said.
The study by Mr. Wang and coauthors was funded by grants from a Swedish government agency and the National Institutes of Health. The researchers and Dr. Luke had no relevant financial disclosures.
FROM PEDIATRICS