Dermatology News

Treatment options for individuals with early-stage hidradenitis suppurativa (HS) vary depending on patient preference and how clinicians define “early” HS. This can be challenging because to date, no Food and Drug Administration–approved treatments exist for early-stage HS and only two biologics exist for moderate to severe disease.

“For someone with occasional nodules and abscesses, we often use antibiotics and topical antiseptics,” Christopher Sayed, MD, a dermatologist at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill, told this news organization. “We may use these daily for weeks or months or just provide them to use for 1-2 weeks at a time for intermittent flares if a patient doesn’t want to take a pill every day,” he said. “For women, hormonal options like oral contraceptive pills and spironolactone can be a great option” if they don’t mind taking a daily pill.

Topical options that Jennifer L. Hsiao, MD, reaches for in her role as director of the HS clinic at the University of Southern California, Los Angeles, include chlorhexidine wash, topical clindamycin, and topical resorcinol. Systemic medications include oral antibiotics such as doxycycline or clindamycin, while hormonal options include oral contraceptives and/or spironolactone for women and finasteride for men.

Metformin Among Options to Consider

According to Dr. Hsiao, other treatment options to consider trying in patients with mild HS include metformin, “especially in patients who also have prediabetes, PCOS, or obesity;” isotretinoin if the patient has concomitant severe acne; botulinum toxin injections; apremilast or topical roflumilast, and antihyperhidrosis medications such as prescription aluminum chloride topicals, glycopyrronium wipes, and glycopyrrolate.

Recommending lifestyle modifications such as smoking cessation and weight loss for patients diagnosed with early-stage HS is “challenging,” Dr. Sayed said, “because the evidence on different triggers and lifestyle modifications isn’t very strong. There can also be a lot of stigmas around weight and smoking in HS, and it can alienate patients to go straight to these topics in the first visit.”

Early Data on Ruxolitinib Cream Promising

At the 2024 annual meeting of the American Academy of Dermatology, researchers reported on the results of a phase 2 study, which found that topical 1.5% ruxolitinib, a Janus kinase (JAK) inhibitor (currently FDA-approved for atopic dermatitis) was effective in reducing abscess and inflammatory nodule count in patients with mild HS. “There is a major need for this kind of option, and the early results are promising,” said Dr. Sayed, who was not involved with the study. “It’s very difficult to get this covered for patients currently since it is off label for HS. We’ve gotten it for a few patients, and one has really liked it, but it’s unclear how consistent the others were with their use, and their level of improvement was not clear to me.”

For mild HS, he added, “the most important area in which we’ve seen growing evidence is around hair removal lasers such as Nd:YAG and alexandrite lasers. Improving access for patients is a major priority in the coming years.”

According to Dr. Hsiao, other approaches being studied for treating mild HS include a topical aryl hydrocarbon receptor agonist known as AT193, and oral medications, such as phosphodiesterase-4 inhibitors. Laser therapies are also being studied, “such as fractional ablative CO₂ laser therapy combined with topical triamcinolone,” she said. “However, the majority of ongoing HS trials are for moderate to severe disease, so there is certainly a need for more investigation into mild HS treatment approaches.”

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Treatment options for individuals with early-stage hidradenitis suppurativa (HS) vary depending on patient preference and how clinicians define “early” HS. This can be challenging because to date, no Food and Drug Administration–approved treatments exist for early-stage HS and only two biologics exist for moderate to severe disease.

“For someone with occasional nodules and abscesses, we often use antibiotics and topical antiseptics,” Christopher Sayed, MD, a dermatologist at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill, told this news organization. “We may use these daily for weeks or months or just provide them to use for 1-2 weeks at a time for intermittent flares if a patient doesn’t want to take a pill every day,” he said. “For women, hormonal options like oral contraceptive pills and spironolactone can be a great option” if they don’t mind taking a daily pill.

Topical options that Jennifer L. Hsiao, MD, reaches for in her role as director of the HS clinic at the University of Southern California, Los Angeles, include chlorhexidine wash, topical clindamycin, and topical resorcinol. Systemic medications include oral antibiotics such as doxycycline or clindamycin, while hormonal options include oral contraceptives and/or spironolactone for women and finasteride for men.

Metformin Among Options to Consider

According to Dr. Hsiao, other treatment options to consider trying in patients with mild HS include metformin, “especially in patients who also have prediabetes, PCOS, or obesity;” isotretinoin if the patient has concomitant severe acne; botulinum toxin injections; apremilast or topical roflumilast, and antihyperhidrosis medications such as prescription aluminum chloride topicals, glycopyrronium wipes, and glycopyrrolate.

Recommending lifestyle modifications such as smoking cessation and weight loss for patients diagnosed with early-stage HS is “challenging,” Dr. Sayed said, “because the evidence on different triggers and lifestyle modifications isn’t very strong. There can also be a lot of stigmas around weight and smoking in HS, and it can alienate patients to go straight to these topics in the first visit.”

Early Data on Ruxolitinib Cream Promising

At the 2024 annual meeting of the American Academy of Dermatology, researchers reported on the results of a phase 2 study, which found that topical 1.5% ruxolitinib, a Janus kinase (JAK) inhibitor (currently FDA-approved for atopic dermatitis) was effective in reducing abscess and inflammatory nodule count in patients with mild HS. “There is a major need for this kind of option, and the early results are promising,” said Dr. Sayed, who was not involved with the study. “It’s very difficult to get this covered for patients currently since it is off label for HS. We’ve gotten it for a few patients, and one has really liked it, but it’s unclear how consistent the others were with their use, and their level of improvement was not clear to me.”

For mild HS, he added, “the most important area in which we’ve seen growing evidence is around hair removal lasers such as Nd:YAG and alexandrite lasers. Improving access for patients is a major priority in the coming years.”

According to Dr. Hsiao, other approaches being studied for treating mild HS include a topical aryl hydrocarbon receptor agonist known as AT193, and oral medications, such as phosphodiesterase-4 inhibitors. Laser therapies are also being studied, “such as fractional ablative CO₂ laser therapy combined with topical triamcinolone,” she said. “However, the majority of ongoing HS trials are for moderate to severe disease, so there is certainly a need for more investigation into mild HS treatment approaches.”

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Treatment options for individuals with early-stage hidradenitis suppurativa (HS) vary depending on patient preference and how clinicians define “early” HS. This can be challenging because to date, no Food and Drug Administration–approved treatments exist for early-stage HS and only two biologics exist for moderate to severe disease.

“For someone with occasional nodules and abscesses, we often use antibiotics and topical antiseptics,” Christopher Sayed, MD, a dermatologist at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill, told this news organization. “We may use these daily for weeks or months or just provide them to use for 1-2 weeks at a time for intermittent flares if a patient doesn’t want to take a pill every day,” he said. “For women, hormonal options like oral contraceptive pills and spironolactone can be a great option” if they don’t mind taking a daily pill.

Topical options that Jennifer L. Hsiao, MD, reaches for in her role as director of the HS clinic at the University of Southern California, Los Angeles, include chlorhexidine wash, topical clindamycin, and topical resorcinol. Systemic medications include oral antibiotics such as doxycycline or clindamycin, while hormonal options include oral contraceptives and/or spironolactone for women and finasteride for men.

Metformin Among Options to Consider

According to Dr. Hsiao, other treatment options to consider trying in patients with mild HS include metformin, “especially in patients who also have prediabetes, PCOS, or obesity;” isotretinoin if the patient has concomitant severe acne; botulinum toxin injections; apremilast or topical roflumilast, and antihyperhidrosis medications such as prescription aluminum chloride topicals, glycopyrronium wipes, and glycopyrrolate.

Recommending lifestyle modifications such as smoking cessation and weight loss for patients diagnosed with early-stage HS is “challenging,” Dr. Sayed said, “because the evidence on different triggers and lifestyle modifications isn’t very strong. There can also be a lot of stigmas around weight and smoking in HS, and it can alienate patients to go straight to these topics in the first visit.”

Early Data on Ruxolitinib Cream Promising

At the 2024 annual meeting of the American Academy of Dermatology, researchers reported on the results of a phase 2 study, which found that topical 1.5% ruxolitinib, a Janus kinase (JAK) inhibitor (currently FDA-approved for atopic dermatitis) was effective in reducing abscess and inflammatory nodule count in patients with mild HS. “There is a major need for this kind of option, and the early results are promising,” said Dr. Sayed, who was not involved with the study. “It’s very difficult to get this covered for patients currently since it is off label for HS. We’ve gotten it for a few patients, and one has really liked it, but it’s unclear how consistent the others were with their use, and their level of improvement was not clear to me.”

For mild HS, he added, “the most important area in which we’ve seen growing evidence is around hair removal lasers such as Nd:YAG and alexandrite lasers. Improving access for patients is a major priority in the coming years.”

According to Dr. Hsiao, other approaches being studied for treating mild HS include a topical aryl hydrocarbon receptor agonist known as AT193, and oral medications, such as phosphodiesterase-4 inhibitors. Laser therapies are also being studied, “such as fractional ablative CO₂ laser therapy combined with topical triamcinolone,” she said. “However, the majority of ongoing HS trials are for moderate to severe disease, so there is certainly a need for more investigation into mild HS treatment approaches.”

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Based on his experience caring for patients with hidradenitis suppurativa (HS), dermatologist Christopher Sayed, MD, said that an exhaustive battery of tests is usually not required to diagnose early-stage HS, which can be mistaken for other conditions, such as an infection, folliculitis, and acne.

According to 2019 guidelines from the United States and Canadian hidradenitis suppurativa foundations, the diagnostic criteria for HS in general are the presence of typical lesions such as abscesses, nodules, and tunnels in classic locations such as underarms, groins, and buttocks that recur over the course of at least 6 months. “There is no need for additional testing or imaging to make the diagnosis,” said Dr. Sayed, co-chair of the 2019 guidelines work group, who sees patients at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill. “In many ways, the diagnosis should be very simple since the presentation is classic in most cases, though it can be confusing in the first 6 months or so.”

Courtesy Dr. Jennifer L. Hsiao

Persistence, Recurrence Major Clues

Prior to being diagnosed with Hurley stage I HS — characterized by recurrent nodules and abscesses with minimal scars, according to the guidelines — most people figure they’ve been getting recurrent Staphylococcus aureus infections or are having trouble with ingrown hairs from shaving, he continued. They may also say they get “boils” without an understanding of what has been causing them.

“Early HS can mimic an intense folliculitis or furuncles that can sometimes be caused by Staphylococcus infections, but the history of persistence or recurrence for months, despite treatment that should cover something like a Staph infection is a major clue,” Dr. Sayed said. “Thanks to improved resources on the internet, more patients, compared to several years ago, come in asking about HS after they’ve done their own research. As public awareness improves, hopefully this trend will grow, and patients will be diagnosed and treated earlier.” Family history is also a strong predictor of HS, since about half of patients have first-degree relatives who have a history of HS, he noted.

Dr. Sayed

The ‘2-2-6 Rule’

When she sees a patient who might have HS, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, follows the “2-2-6 rule,” which involves asking patients if they have had 2 episodes of 2 or more abscesses in 6 months. “If the patient answers yes, there’s a high likelihood that person has HS,” she said.

Hurley stage I HS is defined as nodules and abscesses without sinus tracts (tunnels) or scarring. But in Dr. Hsiao’s opinion, the Hurley staging system “is not the best way to characterize disease activity” because some patients meet criteria for Hurley stage I disease, meaning they do not have any scars or sinus tracts/tunnels, “but they have high disease activity with several inflammatory nodules and large painful abscesses that are limiting their quality of life and ability to function.”

Dr. Hsiao

• Do you have a primary care provider (PCP)? PCPs are important care partners for patients with HS doctor to help screen for the comorbidities associated with the condition.
• What seems to make your HS worse? This can help identify potential triggers to avoid.
• What other medical conditions do you have?
• How would you describe the impact HS has on your quality of life?
• For women: Does your HS get worse around your period? “This can help to identify a potential hormonal trigger,” she said. “If the patient answers ‘yes,’ I would strongly consider a combined oral contraceptive pill and/or spironolactone as part of the patient’s treatment regimen.”

‘Window of Opportunity’ to Intervene

According to Dr. Hsiao, there has been a paradigm shift in the approach to HS management that emphasizes a “window of opportunity,” where earlier initiation of appropriate long-term immunomodulator therapy is recommended to try to mitigate disease progression. The development of tunnels and scars is a telltale sign that permanent tissue destruction is occurring, and the patient’s HS is no longer mild.

Ideally, a conversation about adalimumab, a tumor necrosis factor inhibitor, and secukinumab, an interleukin-17A antagonist (the two currently Food and Drug Administration–approved medications for HS, for moderate to severe disease/Hurley stage II/III) will have already been started with patients prior to development of a high tunnel or scar burden, signs of later-stage disease.

“Medications like this have the potential to slow and prevent that progression and reduce the surgical burden patients face over time, which is a major priority,” Dr. Sayed said. He noted that while comfort level with managing HS can vary among clinicians, “I’d encourage dermatologists to stay engaged with these patients because our training in the medical and surgical management of complex diseases like this is unmatched among other specialties,” he said. “Education of colleagues in other specialties should also be a big priority, especially for those in urgent care, emergency medicine, surgery, and ob.gyn. who often encounter these patients and may be less familiar” with HS.

Besides the North American clinical management guidelines for HS, which are expected to be updated in the next 18-24 months, as well as comorbidity screening recommendations for HS published in 2022, another resource Dr. Sayed and Dr. Hsiao recommend is the HS Foundation website, which features a link to Continuing Medical Education video lectures. The foundation also hosts an annual Symposium on HS Advances. This year’s event is scheduled in November in Austin, Texas.

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Based on his experience caring for patients with hidradenitis suppurativa (HS), dermatologist Christopher Sayed, MD, said that an exhaustive battery of tests is usually not required to diagnose early-stage HS, which can be mistaken for other conditions, such as an infection, folliculitis, and acne.

According to 2019 guidelines from the United States and Canadian hidradenitis suppurativa foundations, the diagnostic criteria for HS in general are the presence of typical lesions such as abscesses, nodules, and tunnels in classic locations such as underarms, groins, and buttocks that recur over the course of at least 6 months. “There is no need for additional testing or imaging to make the diagnosis,” said Dr. Sayed, co-chair of the 2019 guidelines work group, who sees patients at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill. “In many ways, the diagnosis should be very simple since the presentation is classic in most cases, though it can be confusing in the first 6 months or so.”

Courtesy Dr. Jennifer L. Hsiao

Persistence, Recurrence Major Clues

Prior to being diagnosed with Hurley stage I HS — characterized by recurrent nodules and abscesses with minimal scars, according to the guidelines — most people figure they’ve been getting recurrent Staphylococcus aureus infections or are having trouble with ingrown hairs from shaving, he continued. They may also say they get “boils” without an understanding of what has been causing them.

“Early HS can mimic an intense folliculitis or furuncles that can sometimes be caused by Staphylococcus infections, but the history of persistence or recurrence for months, despite treatment that should cover something like a Staph infection is a major clue,” Dr. Sayed said. “Thanks to improved resources on the internet, more patients, compared to several years ago, come in asking about HS after they’ve done their own research. As public awareness improves, hopefully this trend will grow, and patients will be diagnosed and treated earlier.” Family history is also a strong predictor of HS, since about half of patients have first-degree relatives who have a history of HS, he noted.

Dr. Sayed

The ‘2-2-6 Rule’

When she sees a patient who might have HS, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, follows the “2-2-6 rule,” which involves asking patients if they have had 2 episodes of 2 or more abscesses in 6 months. “If the patient answers yes, there’s a high likelihood that person has HS,” she said.

Hurley stage I HS is defined as nodules and abscesses without sinus tracts (tunnels) or scarring. But in Dr. Hsiao’s opinion, the Hurley staging system “is not the best way to characterize disease activity” because some patients meet criteria for Hurley stage I disease, meaning they do not have any scars or sinus tracts/tunnels, “but they have high disease activity with several inflammatory nodules and large painful abscesses that are limiting their quality of life and ability to function.”

Dr. Hsiao

• Do you have a primary care provider (PCP)? PCPs are important care partners for patients with HS doctor to help screen for the comorbidities associated with the condition.
• What seems to make your HS worse? This can help identify potential triggers to avoid.
• What other medical conditions do you have?
• How would you describe the impact HS has on your quality of life?
• For women: Does your HS get worse around your period? “This can help to identify a potential hormonal trigger,” she said. “If the patient answers ‘yes,’ I would strongly consider a combined oral contraceptive pill and/or spironolactone as part of the patient’s treatment regimen.”

‘Window of Opportunity’ to Intervene

According to Dr. Hsiao, there has been a paradigm shift in the approach to HS management that emphasizes a “window of opportunity,” where earlier initiation of appropriate long-term immunomodulator therapy is recommended to try to mitigate disease progression. The development of tunnels and scars is a telltale sign that permanent tissue destruction is occurring, and the patient’s HS is no longer mild.

Ideally, a conversation about adalimumab, a tumor necrosis factor inhibitor, and secukinumab, an interleukin-17A antagonist (the two currently Food and Drug Administration–approved medications for HS, for moderate to severe disease/Hurley stage II/III) will have already been started with patients prior to development of a high tunnel or scar burden, signs of later-stage disease.

“Medications like this have the potential to slow and prevent that progression and reduce the surgical burden patients face over time, which is a major priority,” Dr. Sayed said. He noted that while comfort level with managing HS can vary among clinicians, “I’d encourage dermatologists to stay engaged with these patients because our training in the medical and surgical management of complex diseases like this is unmatched among other specialties,” he said. “Education of colleagues in other specialties should also be a big priority, especially for those in urgent care, emergency medicine, surgery, and ob.gyn. who often encounter these patients and may be less familiar” with HS.

Besides the North American clinical management guidelines for HS, which are expected to be updated in the next 18-24 months, as well as comorbidity screening recommendations for HS published in 2022, another resource Dr. Sayed and Dr. Hsiao recommend is the HS Foundation website, which features a link to Continuing Medical Education video lectures. The foundation also hosts an annual Symposium on HS Advances. This year’s event is scheduled in November in Austin, Texas.

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Based on his experience caring for patients with hidradenitis suppurativa (HS), dermatologist Christopher Sayed, MD, said that an exhaustive battery of tests is usually not required to diagnose early-stage HS, which can be mistaken for other conditions, such as an infection, folliculitis, and acne.

According to 2019 guidelines from the United States and Canadian hidradenitis suppurativa foundations, the diagnostic criteria for HS in general are the presence of typical lesions such as abscesses, nodules, and tunnels in classic locations such as underarms, groins, and buttocks that recur over the course of at least 6 months. “There is no need for additional testing or imaging to make the diagnosis,” said Dr. Sayed, co-chair of the 2019 guidelines work group, who sees patients at the HS and Follicular Disorders Clinic at the University of North Carolina, Chapel Hill. “In many ways, the diagnosis should be very simple since the presentation is classic in most cases, though it can be confusing in the first 6 months or so.”

Courtesy Dr. Jennifer L. Hsiao

Persistence, Recurrence Major Clues

Prior to being diagnosed with Hurley stage I HS — characterized by recurrent nodules and abscesses with minimal scars, according to the guidelines — most people figure they’ve been getting recurrent Staphylococcus aureus infections or are having trouble with ingrown hairs from shaving, he continued. They may also say they get “boils” without an understanding of what has been causing them.

“Early HS can mimic an intense folliculitis or furuncles that can sometimes be caused by Staphylococcus infections, but the history of persistence or recurrence for months, despite treatment that should cover something like a Staph infection is a major clue,” Dr. Sayed said. “Thanks to improved resources on the internet, more patients, compared to several years ago, come in asking about HS after they’ve done their own research. As public awareness improves, hopefully this trend will grow, and patients will be diagnosed and treated earlier.” Family history is also a strong predictor of HS, since about half of patients have first-degree relatives who have a history of HS, he noted.

Dr. Sayed

The ‘2-2-6 Rule’

When she sees a patient who might have HS, Jennifer L. Hsiao, MD, a dermatologist who directs the HS clinic at the University of Southern California, Los Angeles, follows the “2-2-6 rule,” which involves asking patients if they have had 2 episodes of 2 or more abscesses in 6 months. “If the patient answers yes, there’s a high likelihood that person has HS,” she said.

Hurley stage I HS is defined as nodules and abscesses without sinus tracts (tunnels) or scarring. But in Dr. Hsiao’s opinion, the Hurley staging system “is not the best way to characterize disease activity” because some patients meet criteria for Hurley stage I disease, meaning they do not have any scars or sinus tracts/tunnels, “but they have high disease activity with several inflammatory nodules and large painful abscesses that are limiting their quality of life and ability to function.”

Dr. Hsiao

• Do you have a primary care provider (PCP)? PCPs are important care partners for patients with HS doctor to help screen for the comorbidities associated with the condition.
• What seems to make your HS worse? This can help identify potential triggers to avoid.
• What other medical conditions do you have?
• How would you describe the impact HS has on your quality of life?
• For women: Does your HS get worse around your period? “This can help to identify a potential hormonal trigger,” she said. “If the patient answers ‘yes,’ I would strongly consider a combined oral contraceptive pill and/or spironolactone as part of the patient’s treatment regimen.”

‘Window of Opportunity’ to Intervene

According to Dr. Hsiao, there has been a paradigm shift in the approach to HS management that emphasizes a “window of opportunity,” where earlier initiation of appropriate long-term immunomodulator therapy is recommended to try to mitigate disease progression. The development of tunnels and scars is a telltale sign that permanent tissue destruction is occurring, and the patient’s HS is no longer mild.

Ideally, a conversation about adalimumab, a tumor necrosis factor inhibitor, and secukinumab, an interleukin-17A antagonist (the two currently Food and Drug Administration–approved medications for HS, for moderate to severe disease/Hurley stage II/III) will have already been started with patients prior to development of a high tunnel or scar burden, signs of later-stage disease.

“Medications like this have the potential to slow and prevent that progression and reduce the surgical burden patients face over time, which is a major priority,” Dr. Sayed said. He noted that while comfort level with managing HS can vary among clinicians, “I’d encourage dermatologists to stay engaged with these patients because our training in the medical and surgical management of complex diseases like this is unmatched among other specialties,” he said. “Education of colleagues in other specialties should also be a big priority, especially for those in urgent care, emergency medicine, surgery, and ob.gyn. who often encounter these patients and may be less familiar” with HS.

Besides the North American clinical management guidelines for HS, which are expected to be updated in the next 18-24 months, as well as comorbidity screening recommendations for HS published in 2022, another resource Dr. Sayed and Dr. Hsiao recommend is the HS Foundation website, which features a link to Continuing Medical Education video lectures. The foundation also hosts an annual Symposium on HS Advances. This year’s event is scheduled in November in Austin, Texas.

Dr. Sayed disclosed that he is secretary of the HS Foundation and a member of the European HS Foundation. He has served as a consultant for AbbVie, Alumis, AstraZeneca, Incyte, InflaRx, Novartis, Sanofi, Sonoma Biotherapeutics, and UCB; as a speaker for AbbVie, Novartis, and UCB; and as an investigator for Chemocentryx, Incyte, InflaRx, Novartis, and UCB. Dr. Hsiao disclosed that she is a member of the board of directors for the HS Foundation and has served as a consultant for AbbVie, Aclaris, Boehringer Ingelheim, Incyte, Novartis, and UCB; as a speaker for AbbVie, Novartis, Sanofi Regeneron, and UCB; and as an investigator for Amgen, Boehringer Ingelheim, and Incyte.

A version of this article first appeared on Medscape.com.

Tell someone you’re a doctor, and the reaction is often: “You must be rich.” But physicians who are just finishing medical school or are in their early careers might feel far from it. The average medical school debt is more than $200,000, with total debts including undergrad climbing well north of $250,000.

That leaves house-hunting physicians in a predicament. A key factor for lending institutions is the “debt to income” ratio, a calculation which indicates if you already have too much debt to pay your mortgage. That single equation could eliminate you from lenders’ mortgage requirements.

But young doctors are also in a unique situation. Yes, they carry above-average levels of debt, but they are on a path to substantial income in future years. That’s where the physician mortgage loan (PML) becomes a useful option. 

What Is a Physician Mortgage Loan?

A PML is designed to help physicians access mortgages despite large amounts of debt. They are also sometimes available to dentists, veterinarians, podiatrists, and others, according to Stephen Chang, MD, a radiologist, and a managing director at Acts Financial Advisors in McLean, Virginia.

The key features, according to James M. Dahle, MD, an emergency physician and founder of The White Coat Investor, include:

• No required down payment, which is typically 20% with a conventional loan.
• No private mortgage insurance (PMI). This is often a requirement of traditional loans, designed to protect the lender if the buyer misses payments. PMLs don’t involve PMI even if you don’t put down 20%.
• No pay stubs. With a conventional loan, pay stubs are often required to prove income level and reliability. PMLs will often allow an employment contract in place of those. 
• Different consideration of the student loan burden.

Those are the upsides, of course, but there may be downsides. Dr. Dahle said a PML might involve slightly higher rates and fees than a conventional mortgage does but not always.

Who Is Best Suited for a Physician Mortgage Loan?

Financial advisers caution that everyone should first consider their full financial picture before applying for a mortgage, PML or otherwise. “If you don’t have the money saved for a down payment, one can ask if you are financially prepared to purchase a home,” says Cobin Soelberg, MD, an anesthesiologist and owner of Greeley Wealth Management, a financial planning firm serving physician families in Bend, Oregon. 

If your savings are slim, you might need to build those accounts further before pursuing home ownership and the expenses that come along with it.

Your credit score can contribute to the equation. “With any loan product, we always recommend working to optimize your personal credit score as soon as possible before applying for a loan,” said Mark P. Eid, MD, a dermatologist and co–managing director (with Dr. Chang) at Act Financial Advisors. “Once you get into the high 700s, you’ve typically qualified for the best interest rates, so while that perfect 850 is nice to achieve, it’s by no means necessary.”

Also, assess your reasons for purchasing a home and whether it will fit your lifestyle in the coming years. “The main reason that [my wife and I] wanted to buy a home was for stability,” said Jordan Frey, MD, founder of The Prudent Plastic Surgeon. “After living in apartments for years, we wanted a place that was truly our own. We definitely felt disappointed and frustrated when worrying that our student debt may limit our ability to do this.”

Like many physicians, Dr. Frey had taken on a huge amount of debt, to the tune of half a million dollars in student loans and credit card debt when he finished training in 2020. The question Dr. Frey and his wife wrestled with was: “How much debt should we take on in addition to what we already have?”

What Are the Risks? What’s in the Fine Print?

The eased limitations of PMLs come with potential pitfalls, and physicians should not imagine that they have unlimited buying power.

“Many physicians buy more expensive or bigger houses than they need simply because banks are willing to lend physicians money,” Dr. Soelberg warns. “So, the doctor gets locked into a large mortgage and cannot build wealth, save for retirement, and repay their student loans.” 

As you shop around, beware of omissions and scams. When meeting with lenders, Dr. Frey recalled that some didn’t even present PMLs as an option, and others presented them with unfavorable terms. He was careful to look for disadvantages hidden in the fine print, such as a potential “big hike in the rate a year later.” 

But sometimes, a scam is not outright deception but is more like temptation. So it’s important to have your own best interests in mind without relying on lenders’ advice. 

“When we were shopping around, some mortgage lenders would [offer] $1.5 million, and we thought ‘that makes no sense,’ ” said Dr. Frey. “[Physicians] have big future income, which makes us attractive to these lenders. No one in their right mind would give a mortgage like this to anyone else. They aren’t worried about whether it’s a smart decision for you or not.” 

What Other Red Flags Should You Look Out for?

Dr. Frey recommends medical professionals beware of these red flags when shopping for PMLs:

• A request for any type of collateral, including your medical practice
• A rate that is much higher than others
• A lender is pushing you to borrow a higher amount than you’re comfortable with 
• A lender attempts to influence your decision about the size of your down payment

Remember, if you are choosing an adjustable-rate mortgage (ARM), your rate will recalibrate on the basis of the market’s rates — for better or worse. This means that your payment might be higher or lower, taking current interest rates into account, based on the market.

Looking back, Dr. Frey said he might reconsider his decision to use a 10-year ARM. He and his wife chose it because the rate was low at the time, and they planned to pay off the mortgage quickly or move before it went up. But the uncertainty added an element of pressure. 

How Can PMLs Contribute to Overall Financial Health?

Dr. Frey says his physician mortgage was “a huge advantage,” allowing him and his wife to put 0% down on their home without PMI. But most importantly, it fit within their overall financial plan, which included investing. “The money that we would have potentially used for a down payment, we used to buy a rental property, which then got us more income,” he says. 

Of course, buying a rental property is not the only path to financial health and freedom. Many people approach a home as an investment that will eventually become fully their own. Others might put that down payment toward building a safety net of savings accounts. 

Used strategically and intentionally, PMLs can put you on a more predictable financial path. And with less money stress, buying a home can be an exciting milestone as you plan your future and put down roots in a community.

A version of this article appeared on Medscape.com.

Tell someone you’re a doctor, and the reaction is often: “You must be rich.” But physicians who are just finishing medical school or are in their early careers might feel far from it. The average medical school debt is more than $200,000, with total debts including undergrad climbing well north of $250,000.

That leaves house-hunting physicians in a predicament. A key factor for lending institutions is the “debt to income” ratio, a calculation which indicates if you already have too much debt to pay your mortgage. That single equation could eliminate you from lenders’ mortgage requirements.

But young doctors are also in a unique situation. Yes, they carry above-average levels of debt, but they are on a path to substantial income in future years. That’s where the physician mortgage loan (PML) becomes a useful option. 

What Is a Physician Mortgage Loan?

A PML is designed to help physicians access mortgages despite large amounts of debt. They are also sometimes available to dentists, veterinarians, podiatrists, and others, according to Stephen Chang, MD, a radiologist, and a managing director at Acts Financial Advisors in McLean, Virginia.

The key features, according to James M. Dahle, MD, an emergency physician and founder of The White Coat Investor, include:

• No required down payment, which is typically 20% with a conventional loan.
• No private mortgage insurance (PMI). This is often a requirement of traditional loans, designed to protect the lender if the buyer misses payments. PMLs don’t involve PMI even if you don’t put down 20%.
• No pay stubs. With a conventional loan, pay stubs are often required to prove income level and reliability. PMLs will often allow an employment contract in place of those. 
• Different consideration of the student loan burden.

Those are the upsides, of course, but there may be downsides. Dr. Dahle said a PML might involve slightly higher rates and fees than a conventional mortgage does but not always.

Who Is Best Suited for a Physician Mortgage Loan?

Financial advisers caution that everyone should first consider their full financial picture before applying for a mortgage, PML or otherwise. “If you don’t have the money saved for a down payment, one can ask if you are financially prepared to purchase a home,” says Cobin Soelberg, MD, an anesthesiologist and owner of Greeley Wealth Management, a financial planning firm serving physician families in Bend, Oregon. 

If your savings are slim, you might need to build those accounts further before pursuing home ownership and the expenses that come along with it.

Your credit score can contribute to the equation. “With any loan product, we always recommend working to optimize your personal credit score as soon as possible before applying for a loan,” said Mark P. Eid, MD, a dermatologist and co–managing director (with Dr. Chang) at Act Financial Advisors. “Once you get into the high 700s, you’ve typically qualified for the best interest rates, so while that perfect 850 is nice to achieve, it’s by no means necessary.”

Also, assess your reasons for purchasing a home and whether it will fit your lifestyle in the coming years. “The main reason that [my wife and I] wanted to buy a home was for stability,” said Jordan Frey, MD, founder of The Prudent Plastic Surgeon. “After living in apartments for years, we wanted a place that was truly our own. We definitely felt disappointed and frustrated when worrying that our student debt may limit our ability to do this.”

Like many physicians, Dr. Frey had taken on a huge amount of debt, to the tune of half a million dollars in student loans and credit card debt when he finished training in 2020. The question Dr. Frey and his wife wrestled with was: “How much debt should we take on in addition to what we already have?”

What Are the Risks? What’s in the Fine Print?

The eased limitations of PMLs come with potential pitfalls, and physicians should not imagine that they have unlimited buying power.

“Many physicians buy more expensive or bigger houses than they need simply because banks are willing to lend physicians money,” Dr. Soelberg warns. “So, the doctor gets locked into a large mortgage and cannot build wealth, save for retirement, and repay their student loans.” 

As you shop around, beware of omissions and scams. When meeting with lenders, Dr. Frey recalled that some didn’t even present PMLs as an option, and others presented them with unfavorable terms. He was careful to look for disadvantages hidden in the fine print, such as a potential “big hike in the rate a year later.” 

But sometimes, a scam is not outright deception but is more like temptation. So it’s important to have your own best interests in mind without relying on lenders’ advice. 

“When we were shopping around, some mortgage lenders would [offer] $1.5 million, and we thought ‘that makes no sense,’ ” said Dr. Frey. “[Physicians] have big future income, which makes us attractive to these lenders. No one in their right mind would give a mortgage like this to anyone else. They aren’t worried about whether it’s a smart decision for you or not.” 

What Other Red Flags Should You Look Out for?

Dr. Frey recommends medical professionals beware of these red flags when shopping for PMLs:

• A request for any type of collateral, including your medical practice
• A rate that is much higher than others
• A lender is pushing you to borrow a higher amount than you’re comfortable with 
• A lender attempts to influence your decision about the size of your down payment

Remember, if you are choosing an adjustable-rate mortgage (ARM), your rate will recalibrate on the basis of the market’s rates — for better or worse. This means that your payment might be higher or lower, taking current interest rates into account, based on the market.

Looking back, Dr. Frey said he might reconsider his decision to use a 10-year ARM. He and his wife chose it because the rate was low at the time, and they planned to pay off the mortgage quickly or move before it went up. But the uncertainty added an element of pressure. 

How Can PMLs Contribute to Overall Financial Health?

Dr. Frey says his physician mortgage was “a huge advantage,” allowing him and his wife to put 0% down on their home without PMI. But most importantly, it fit within their overall financial plan, which included investing. “The money that we would have potentially used for a down payment, we used to buy a rental property, which then got us more income,” he says. 

Of course, buying a rental property is not the only path to financial health and freedom. Many people approach a home as an investment that will eventually become fully their own. Others might put that down payment toward building a safety net of savings accounts. 

Used strategically and intentionally, PMLs can put you on a more predictable financial path. And with less money stress, buying a home can be an exciting milestone as you plan your future and put down roots in a community.

A version of this article appeared on Medscape.com.

Tell someone you’re a doctor, and the reaction is often: “You must be rich.” But physicians who are just finishing medical school or are in their early careers might feel far from it. The average medical school debt is more than $200,000, with total debts including undergrad climbing well north of $250,000.

That leaves house-hunting physicians in a predicament. A key factor for lending institutions is the “debt to income” ratio, a calculation which indicates if you already have too much debt to pay your mortgage. That single equation could eliminate you from lenders’ mortgage requirements.

But young doctors are also in a unique situation. Yes, they carry above-average levels of debt, but they are on a path to substantial income in future years. That’s where the physician mortgage loan (PML) becomes a useful option. 

What Is a Physician Mortgage Loan?

A PML is designed to help physicians access mortgages despite large amounts of debt. They are also sometimes available to dentists, veterinarians, podiatrists, and others, according to Stephen Chang, MD, a radiologist, and a managing director at Acts Financial Advisors in McLean, Virginia.

The key features, according to James M. Dahle, MD, an emergency physician and founder of The White Coat Investor, include:

• No required down payment, which is typically 20% with a conventional loan.
• No private mortgage insurance (PMI). This is often a requirement of traditional loans, designed to protect the lender if the buyer misses payments. PMLs don’t involve PMI even if you don’t put down 20%.
• No pay stubs. With a conventional loan, pay stubs are often required to prove income level and reliability. PMLs will often allow an employment contract in place of those. 
• Different consideration of the student loan burden.

Those are the upsides, of course, but there may be downsides. Dr. Dahle said a PML might involve slightly higher rates and fees than a conventional mortgage does but not always.

Who Is Best Suited for a Physician Mortgage Loan?

Financial advisers caution that everyone should first consider their full financial picture before applying for a mortgage, PML or otherwise. “If you don’t have the money saved for a down payment, one can ask if you are financially prepared to purchase a home,” says Cobin Soelberg, MD, an anesthesiologist and owner of Greeley Wealth Management, a financial planning firm serving physician families in Bend, Oregon. 

If your savings are slim, you might need to build those accounts further before pursuing home ownership and the expenses that come along with it.

Your credit score can contribute to the equation. “With any loan product, we always recommend working to optimize your personal credit score as soon as possible before applying for a loan,” said Mark P. Eid, MD, a dermatologist and co–managing director (with Dr. Chang) at Act Financial Advisors. “Once you get into the high 700s, you’ve typically qualified for the best interest rates, so while that perfect 850 is nice to achieve, it’s by no means necessary.”

Also, assess your reasons for purchasing a home and whether it will fit your lifestyle in the coming years. “The main reason that [my wife and I] wanted to buy a home was for stability,” said Jordan Frey, MD, founder of The Prudent Plastic Surgeon. “After living in apartments for years, we wanted a place that was truly our own. We definitely felt disappointed and frustrated when worrying that our student debt may limit our ability to do this.”

Like many physicians, Dr. Frey had taken on a huge amount of debt, to the tune of half a million dollars in student loans and credit card debt when he finished training in 2020. The question Dr. Frey and his wife wrestled with was: “How much debt should we take on in addition to what we already have?”

What Are the Risks? What’s in the Fine Print?

The eased limitations of PMLs come with potential pitfalls, and physicians should not imagine that they have unlimited buying power.

“Many physicians buy more expensive or bigger houses than they need simply because banks are willing to lend physicians money,” Dr. Soelberg warns. “So, the doctor gets locked into a large mortgage and cannot build wealth, save for retirement, and repay their student loans.” 

As you shop around, beware of omissions and scams. When meeting with lenders, Dr. Frey recalled that some didn’t even present PMLs as an option, and others presented them with unfavorable terms. He was careful to look for disadvantages hidden in the fine print, such as a potential “big hike in the rate a year later.” 

But sometimes, a scam is not outright deception but is more like temptation. So it’s important to have your own best interests in mind without relying on lenders’ advice. 

“When we were shopping around, some mortgage lenders would [offer] $1.5 million, and we thought ‘that makes no sense,’ ” said Dr. Frey. “[Physicians] have big future income, which makes us attractive to these lenders. No one in their right mind would give a mortgage like this to anyone else. They aren’t worried about whether it’s a smart decision for you or not.” 

What Other Red Flags Should You Look Out for?

Dr. Frey recommends medical professionals beware of these red flags when shopping for PMLs:

• A request for any type of collateral, including your medical practice
• A rate that is much higher than others
• A lender is pushing you to borrow a higher amount than you’re comfortable with 
• A lender attempts to influence your decision about the size of your down payment

Remember, if you are choosing an adjustable-rate mortgage (ARM), your rate will recalibrate on the basis of the market’s rates — for better or worse. This means that your payment might be higher or lower, taking current interest rates into account, based on the market.

Looking back, Dr. Frey said he might reconsider his decision to use a 10-year ARM. He and his wife chose it because the rate was low at the time, and they planned to pay off the mortgage quickly or move before it went up. But the uncertainty added an element of pressure. 

How Can PMLs Contribute to Overall Financial Health?

Dr. Frey says his physician mortgage was “a huge advantage,” allowing him and his wife to put 0% down on their home without PMI. But most importantly, it fit within their overall financial plan, which included investing. “The money that we would have potentially used for a down payment, we used to buy a rental property, which then got us more income,” he says. 

Of course, buying a rental property is not the only path to financial health and freedom. Many people approach a home as an investment that will eventually become fully their own. Others might put that down payment toward building a safety net of savings accounts. 

Used strategically and intentionally, PMLs can put you on a more predictable financial path. And with less money stress, buying a home can be an exciting milestone as you plan your future and put down roots in a community.

A version of this article appeared on Medscape.com.

For decades, physicians and nurses who ventured across state lines to practice, particularly in locum tenens roles, have reaped the benefits of medical licensure compacts. Yet, the same courtesy has eluded physician assistants (PAs), until now. The introduction of the PA Licensure Compact (PA Compact) marks a long-awaited and significant step forward for the PA community.

In April, Virginia Governor Glenn Youngkin signed the bill enacting the PA Compact making Virginia the seventh state to join. The legislation opens a cross-state agreement with seven states and finally allows locum tenens PAs to practice across these state’s borders.

How the PA Compact Works

The interstate arrangement recognizes valid, unencumbered PA licenses issued by other states in the compact. PAs working within the seven states won’t need a separate license from any of those states to practice.

The states include Delaware, Nebraska, Utah, Washington, West Virginia, Wisconsin, and Virginia. While the compact has been approved, the American Academy of Physician Associates said it could take an additional 18-24 months for the states to execute it, giving PAs the access they need to work in the compact states.

How the PA Compact Helps

The PA Compact holds the promise of alleviating some of the travel barriers that PAs often encounter, especially when they work locum tenens or in telehealth and must traverse state lines to deliver essential healthcare. This agreement not only enhances healthcare access but also empowers facilities to recruit new PAs, thereby bridging gaps in their healthcare staffing and addressing public health emergencies more effectively.

PAs will also gain increased flexibility and additional opportunities to earn and benefit from the right to practice in more states without requiring a time-consuming and expensive licensure from each state.

One motivating factor behind developing an interstate compact for physician assistants is that the same types of compacts for physicians and nurses are highly successful. The Nurse Licensure Compact and the Interstate Medical Licensure Compact for physicians encompass 37 and 41 states, respectively. While the seven-state PA Compact is in its earliest stages, it will likely be equally beneficial for PAs.

A survey by Barton Associates found that 95% of PAs said they would be more likely to consider working in a different state if the PA Compact made it more accessible.

Other states have begun legislation to enact a PA Compact, including Colorado, New Hampshire, Maine, Michigan New York, Ohio, Oklahoma, Rhode Island, Tennessee, and Vermont. 

If your state still needs to enact a compact or file for compact legislation, let your elected officials know that the PAs in your state want to join a compact. 
 

A version of this article appeared on Medscape.com .

For decades, physicians and nurses who ventured across state lines to practice, particularly in locum tenens roles, have reaped the benefits of medical licensure compacts. Yet, the same courtesy has eluded physician assistants (PAs), until now. The introduction of the PA Licensure Compact (PA Compact) marks a long-awaited and significant step forward for the PA community.

In April, Virginia Governor Glenn Youngkin signed the bill enacting the PA Compact making Virginia the seventh state to join. The legislation opens a cross-state agreement with seven states and finally allows locum tenens PAs to practice across these state’s borders.

How the PA Compact Works

The interstate arrangement recognizes valid, unencumbered PA licenses issued by other states in the compact. PAs working within the seven states won’t need a separate license from any of those states to practice.

The states include Delaware, Nebraska, Utah, Washington, West Virginia, Wisconsin, and Virginia. While the compact has been approved, the American Academy of Physician Associates said it could take an additional 18-24 months for the states to execute it, giving PAs the access they need to work in the compact states.

How the PA Compact Helps

The PA Compact holds the promise of alleviating some of the travel barriers that PAs often encounter, especially when they work locum tenens or in telehealth and must traverse state lines to deliver essential healthcare. This agreement not only enhances healthcare access but also empowers facilities to recruit new PAs, thereby bridging gaps in their healthcare staffing and addressing public health emergencies more effectively.

PAs will also gain increased flexibility and additional opportunities to earn and benefit from the right to practice in more states without requiring a time-consuming and expensive licensure from each state.

One motivating factor behind developing an interstate compact for physician assistants is that the same types of compacts for physicians and nurses are highly successful. The Nurse Licensure Compact and the Interstate Medical Licensure Compact for physicians encompass 37 and 41 states, respectively. While the seven-state PA Compact is in its earliest stages, it will likely be equally beneficial for PAs.

A survey by Barton Associates found that 95% of PAs said they would be more likely to consider working in a different state if the PA Compact made it more accessible.

Other states have begun legislation to enact a PA Compact, including Colorado, New Hampshire, Maine, Michigan New York, Ohio, Oklahoma, Rhode Island, Tennessee, and Vermont. 

If your state still needs to enact a compact or file for compact legislation, let your elected officials know that the PAs in your state want to join a compact. 
 

A version of this article appeared on Medscape.com .

For decades, physicians and nurses who ventured across state lines to practice, particularly in locum tenens roles, have reaped the benefits of medical licensure compacts. Yet, the same courtesy has eluded physician assistants (PAs), until now. The introduction of the PA Licensure Compact (PA Compact) marks a long-awaited and significant step forward for the PA community.

In April, Virginia Governor Glenn Youngkin signed the bill enacting the PA Compact making Virginia the seventh state to join. The legislation opens a cross-state agreement with seven states and finally allows locum tenens PAs to practice across these state’s borders.

How the PA Compact Works

The interstate arrangement recognizes valid, unencumbered PA licenses issued by other states in the compact. PAs working within the seven states won’t need a separate license from any of those states to practice.

The states include Delaware, Nebraska, Utah, Washington, West Virginia, Wisconsin, and Virginia. While the compact has been approved, the American Academy of Physician Associates said it could take an additional 18-24 months for the states to execute it, giving PAs the access they need to work in the compact states.

How the PA Compact Helps

The PA Compact holds the promise of alleviating some of the travel barriers that PAs often encounter, especially when they work locum tenens or in telehealth and must traverse state lines to deliver essential healthcare. This agreement not only enhances healthcare access but also empowers facilities to recruit new PAs, thereby bridging gaps in their healthcare staffing and addressing public health emergencies more effectively.

PAs will also gain increased flexibility and additional opportunities to earn and benefit from the right to practice in more states without requiring a time-consuming and expensive licensure from each state.

One motivating factor behind developing an interstate compact for physician assistants is that the same types of compacts for physicians and nurses are highly successful. The Nurse Licensure Compact and the Interstate Medical Licensure Compact for physicians encompass 37 and 41 states, respectively. While the seven-state PA Compact is in its earliest stages, it will likely be equally beneficial for PAs.

A survey by Barton Associates found that 95% of PAs said they would be more likely to consider working in a different state if the PA Compact made it more accessible.

Other states have begun legislation to enact a PA Compact, including Colorado, New Hampshire, Maine, Michigan New York, Ohio, Oklahoma, Rhode Island, Tennessee, and Vermont. 

If your state still needs to enact a compact or file for compact legislation, let your elected officials know that the PAs in your state want to join a compact. 
 

A version of this article appeared on Medscape.com .

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

Over the past few decades, the US Food and Drug Administration (FDA) has increasingly relied on surrogate measures such as blood tests instead of clinical outcomes for medication approvals. But critics say the agency lacks consistent standards to ensure the surrogate aligns with clinical outcomes that matter to patients — things like improvements in symptoms and gains in function.

Sometimes those decisions backfire. Consider: In July 2021, the FDA approved aducanumab for the treatment of Alzheimer’s disease, bucking the advice of an advisory panel for the agency that questioned the effectiveness of the medication. Regulators relied on data from the drugmaker, Biogen, showing the monoclonal antibody could reduce levels of amyloid beta plaques in blood — a surrogate marker officials hoped would translate to clinical benefit.

The FDA’s decision triggered significant controversy, and Biogen in January announced it is pulling it from the market this year, citing disappointing sales.

Although the case of aducanumab might seem extreme, given the stakes — Alzheimer’s remains a disease without an effective treatment — it’s far from unusual.

“When we prescribe a drug, there is an underlying assumption that the FDA has done its due diligence to confirm the drug is safe and of benefit,” said Reshma Ramachandran, MD, MPP, MHS, a researcher at Yale School of Medicine, New Haven, Connecticut, and a coauthor of a recent review of surrogate outcomes. “In fact, we found either no evidence or low-quality evidence.” Such markers are associated with clinical outcomes. “We just don’t know if they work meaningfully to treat the patient’s condition. The results were pretty shocking for us,” she said.

The FDA in 2018 released an Adult Surrogate Endpoint Table listing markers that can be used as substitutes for clinical outcomes to more quickly test, review, and approve new therapies. The analysis found the majority of these endpoints lacked subsequent confirmations, defined as published meta-analyses of clinical studies to validate the association between the marker and a clinical outcome important to patients.

In a paper published in JAMA, Dr. Ramachandran and her colleagues looked at 37 surrogate endpoints for nearly 3 dozen nononcologic diseases in the table.

Approval with surrogate markers implies responsibility for postapproval or validation studies — not just lab measures or imaging findings but mortality, morbidity, or improved quality of life, said Joshua D. Wallach, PhD, MS, assistant professor in the department of epidemiology at the Emory Rollins School of Public Health in Atlanta and lead author of the JAMA review.

Dr. Wallach said surrogate markers are easier to measure and do not require large and long trials. But the FDA has not provided clear rules for what makes a surrogate marker valid in clinical trials.

“They’ve said that at a minimum, it requires meta-analytical evidence from studies that have looked at the correlation or the association between the surrogate and the clinical outcome,” Dr. Wallach said. “Our understanding was that if that’s a minimum expectation, we should be able to find those studies in the literature. And the reality is that we were unable to find evidence from those types of studies supporting the association between the surrogate and the clinical outcome.”

Physicians generally do not receive training about the FDA approval process and the difference between biomarkers, surrogate markers, and clinical endpoints, Dr. Ramachandran said. “Our study shows that things are much more uncertain than we thought when it comes to the prescribing of new drugs,” she said.
 

Surrogate Markers on the Rise

Dr. Wallach’s group looked for published meta-analyses compiling randomized controlled trials reporting surrogate endpoints for more than 3 dozen chronic nononcologic conditions, including type 2 diabetes, Alzheimer’s, kidney disease, HIV, gout, and lupus. They found no meta-analyses at all for 59% of the surrogate markers, while for those that were studied, few reported high-strength evidence of an association with clinical outcomes.

The findings echo previous research. In a 2020 study in JAMA Network Open, researchers tallied primary endpoints for all FDA approvals of new drugs and therapies during three 3-year periods: 1995-1997, 2005-2007, and 2015-2017. The proportion of products whose approvals were based on the use of clinical endpoints decreased from 43.8% in 1995-1997 to 28.4% in 2005-2007 to 23.3% in 2015-2017. The share based on surrogate endpoints rose from 43.3% to roughly 60% over the same interval.

A 2017 study in the Journal of Health Economics found the use of “imperfect” surrogate endpoints helped support the approval of an average of 16 new drugs per year between 2010 and 2014 compared with six per year from 1998 to 2008.

Similar concerns about weak associations between surrogate markers and drugs used to treat cancer have been documented before, including in a 2020 study published in eClinicalMedicine. The researchers found the surrogate endpoints in the FDA table either were not tested or were tested but proven to be weak surrogates.

“And yet the FDA considered these as good enough not only for accelerated approval but also for regular approval,” said Bishal Gyawali, MD, PhD, associate professor in the department of oncology at Queen’s University, Kingston, Ontario, Canada, who led the group.

The use of surrogate endpoints is also increasing in Europe, said Huseyin Naci, MHS, PhD, associate professor of health policy at the London School of Economics and Political Science in England. He cited a cohort study of 298 randomized clinical trials (RCTs) in JAMA Oncology suggesting “contemporary oncology RCTs now largely measure putative surrogate endpoints.” Dr. Wallach called the FDA’s surrogate table “a great first step toward transparency. But a key column is missing from that table, telling us what is the basis for which the FDA allows drug companies to use the recognized surrogate markers. What is the evidence they are considering?”

If the agency allows companies the flexibility to validate surrogate endpoints, postmarketing studies designed to confirm the clinical utility of those endpoints should follow.

“We obviously want physicians to be guided by evidence when they’re selecting treatments, and they need to be able to interpret the clinical benefits of the drug that they’re prescribing,” he said. “This is really about having the research consumer, patients, and physicians, as well as industry, understand why certain markers are considered and not considered.”

Dr. Wallach reported receiving grants from the FDA (through the Yale University — Mayo Clinic Center of Excellence in Regulatory Science and Innovation), National Institute on Alcohol Abuse and Alcoholism (1K01AA028258), and Johnson & Johnson (through the Yale University Open Data Access Project); and consulting fees from Hagens Berman Sobol Shapiro LLP and Dugan Law Firm APLC outside the submitted work. Dr. Ramachandran reported receiving grants from the Stavros Niarchos Foundation and FDA; receiving consulting fees from ReAct Action on Antibiotic Resistance strategy policy program outside the submitted work; and serving in an unpaid capacity as chair of the FDA task force for the nonprofit organization Doctors for America and in an unpaid capacity as board president for Universities Allied for Essential Medicines North America.
 

A version of this article appeared on Medscape.com.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Lipoid proteinosis, or Urbach-Wiethe disease, is a rare autosomal recessive genodermatosis with a global prevalence of less than 500 reported cases, with an equal distribution across genders and ethnicities.¹ It is caused by mutations in the ECM1 gene² on chromosome 1q21. This leads to the abnormal deposition of hyaline material in various tissues across different organ systems, with the classic manifestations known as the “string of pearls” sign and a hoarse cry or voice.

The rarity of lipoid proteinosis often leads to challenges in diagnosis. Particularly when deviating from the common association with consanguinity, the potential for de novo mutations or a broader genetic variability in disease expression is highlighted. Our patient presents with symptoms that are pathognomonic to LP with moniliform blepharosis and hoarseness of the voice, in addition to scarring of the extremities. 

Other common clinical manifestations in patients with LP include cobblestoning of the mucosa; hyperkeratosis of the elbows, knees, and hands; and calcification of the amygdala with neuroimaging.³

Genetic testing that identifies a loss-of-function mutation in ECM1 offers diagnostic confirmation. Patients often need multidisciplinary care involving dermatology; ear, nose, throat; neurology; and genetics. Treatment of LP is mostly symptomatic with unsatisfactory resolution of cutaneous changes, with retinoids such as acitretin used as the first-line option and surgery as a consideration for laryngeal hyaline deposits.² Although LP can affect different organ systems, patients tend to have a normal lifespan.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Mcgrath JA. Handb Clin Neurol. 2015:132:317-22. doi: 10.1016/B978-0-444-62702-5.00023-8.

2. Hamada Tet al. Hum Mol Genet. 2002 Apr 1;11(7):833-40. doi: 10.1093/hmg/11.7.833.

3. Frenkel B et al. Clin Oral Investig. 2017 Sep;21(7):2245-51 doi: 10.1007/s00784-016-2017-7.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic & Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic & Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.

Macadamia (Macadamia tetraphylla) is endemic to Australia and is now commercially cultivated worldwide.¹ It is closely related genetically to the other macadamia plants, including the other main one, M. integrifolia, cultivated for macadamia nuts. Known in Brazil as sapucaia or castanha-de-sapucaia, Lecythis pisonis (also referred to as “cream nut” or “monkey pot”) is a large, deciduous tropical tree and member of the Brazil nut family, Lecythidaceae.² Various parts of both of these plants have been associated with medicinal properties, including the potential for dermatologic activity. Notably, the leaves of L. pisonis have been used in traditional medicine to treat pruritus.²This column focuses on the studies suggesting the possible benefits of macadamia and sapucaia components for skin care.

Macadamia

Extraction to Harness Antioxidant Activity

In 2015, Dailey and Vuong developed an aqueous extraction process to recover the phenolic content and antioxidant functionality from the skin waste of M. tetraphylla using response surface methodology. As an environmentally suitable solvent that is also cheap and safe, water was chosen to maximize the extraction scenario. They identified the proper conditions (90° C, a time of 20 min, and a sample-to-solvent ratio of 5 g/100 mL) to obtain sufficient phenolic compounds, proanthocyanidins, and flavonoids to render robust antioxidant function.¹

Baumann Cosmetic & Research Institute

Early in 2023, Somwongin et al. investigated various green extraction methods for viability in harnessing the cosmetic/cosmeceutical ingredients of M. integrifolia pericarps. Extracts were assessed for total phenolic content as well as antioxidant and anti–skin aging functions. They found that among the green extraction methods (ultrasound, micellar, microwave, and pulsed electric field extraction with water used as a clean solvent), the ultrasound-assisted extraction method netted the greatest yield and total phenolic content. It was also associated with the most robust antioxidant and anti–skin aging activities. Indeed, the researchers reported that its antioxidant activities were comparable to ascorbic acid and Trolox and its anti–skin aging potency on a par with epigallocatechin-3-gallate and oleanolic acid. The ultrasound-assisted extract was also deemed safe as it did not provoke irritation. The authors concluded that this environmentally suitable extraction method for M. integrifolia is appropriate for obtaining effective macadamia extracts for use in cosmetics and cosmeceuticals.³

Anti-Aging Activity

In 2017, Addy et al. set out to characterize skin surface lipid composition and differences in an age- and sex-controlled population as a foundation for developing a botanically derived skin surface lipid mimetic agent. They noted that fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and squalene are the main constituents of skin surface lipids. The investigators obtained skin surface lipid samples from the foreheads of 59 healthy 22-year-old women, analyzed them, and used the raw components of M. integrifolia, Simmondsia chinensis, and Olea europaea to engineer a mimetic product. They reported that the esterification reactions of jojoba, macadamia, and tall oils, combined with squalene derived from O. europaea, yielded an appropriate skin surface lipid mimetic, which, when applied to delipidized skin, assisted in recovering barrier function, enhancing skin hydration, and improving elasticity as well as firmness in aged skin. The researchers concluded that this skin surface lipid mimetic could serve as an effective supplement to human skin surface lipids in aged skin and for conditions in which the stratum corneum is impaired.⁴

Two years later, Hanum et al. compared the effects of macadamia nut oil nanocream and conventional cream for treating cutaneous aging over a 4-week period. The macadamia nut oil nanocream, which contained macadamia nut oil 10%, tween 80, propylene glycol, cetyl alcohol, methylparaben, propylparaben, and distilled water, was compared with the conventional cream based on effects on moisture, evenness, pore size, melanin, and wrinkling. The macadamia nut oil was found to yield superior anti-aging activity along each parameter as compared with the conventional cream. The researchers concluded that the macadamia nut oil in nanocream can be an effective formulation for providing benefits in addressing cutaneous aging.⁵

Matthieu Sontag/Wikimedia Commons/CC-BY-SA

Antifungal Activity

In 2015, Vieira et al. characterized 12 fractions enriched in peptides derived from L. pisonis seeds to determine inhibitory activity against Candida albicans. The fraction that exerted the strongest activity at 10 μg/mL, suppressing C. albicans growth by 38.5% and inducing a 69.3% loss of viability, was identified as similar to plant defensins and thus dubbed “L. pisonis defensin 1 (Lp-Def1).” The investigators concluded that Lp-Def1 acts on C. albicans by slightly elevating the induction of reactive oxygen species and causing a significant reduction in mitochondrial activity. They suggested that their findings support the use of plant defensins, particularly Lp-Def1, in the formulation of antifungal products, especially to address C. albicans.¹⁰

Pruritus

In 2012, Silva et al. studied the antipruritic impact of L. pisonis leaf extracts in mice and rats. Pretreatment with the various fractions of L. pisonis as well as constituent mixed triterpenes (ursolic and oleanolic acids) significantly blocked scratching behavior provoked by compound 48/80. The degranulation of rat peritoneal mast cells caused by compound 48/80 was also substantially decreased from pretreatment with the ethanol extract of L. pisonis, ether-L. pisonis fraction, and mixed triterpenes. The L. pisonis ether fraction suppressed edema induced by carrageenan administration and the ethanol extract displayed no toxicity up to an oral dose of 2g/kg. The investigators concluded that their results strongly support the antipruritic effects of L. pisonis leaves as well as the traditional use of the plant to treat pruritus.²

Stability for Cosmetic Creams

In 2020, Rampazzo et al. assessed the stability and cytotoxicity of a cosmetic cream containing sapucaia nut oil. All three tested concentrations (1%, 5%, and 10%) of the cream were found to be stable, with an effective preservative system, and deemed safe for use on human skin. To maintain a pH appropriate for a body cream, the formulation requires a stabilizing agent. The cream with 5% nut oil was identified as the most stable and satisfying for use on the skin.⁷

More recently, Hertel Pereira et al. investigated the benefits of using L. pisonis pericarp extract, known to exhibit abundant antioxidants, in an all-natural skin cream. They found that formulation instability increased proportionally with the concentration of the extract, but the use of the outer pericarp of L. pisonis was well suited for the cream formulation, with physical-chemical and organoleptic qualities unchanged after the stability test.¹¹

Conclusion

The available literature on the medical applications of macadamia and sapucaia plants is sparse. Some recent findings are promising regarding possible uses in skin health. However, much more research is necessary before considering macadamia and sapucaia as viable sources of botanical agents capable of delivering significant cutaneous benefits.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur in Miami. She founded the division of cosmetic dermatology at the University of Miami in 1997. The third edition of her bestselling textbook, “Cosmetic Dermatology,” was published in 2022. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Johnson & Johnson, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., an SaaS company used to generate skin care routines in office and as an e-commerce solution. Write to her at [email protected].

References

1. Dailey A and Vuong QV. Antioxidants (Basel). 2015 Nov 12;4(4):699-718.

2. Silva LL et al. J Ethnopharmacol. 2012 Jan 6;139(1):90-97.

3. Somwongin S et al. Ultrason Sonochem. 2023 Jan;92:106266.

4. Addy J et al. J Cosmet Sci. 2017 Jan/Feb;68(1):59-67.

5. Hanum TI et al. Open Access Maced J Med Sci. 2019 Nov 14;7(22):3917-3920.

6. Akhtar N and Yazan Y. Pak J Pharm Sci. 2008 Jan;21(1):45-50.

7. Rampazzo APS et al. J Cosmet Sci. 2020 Sep/Oct;71(5):239-250.

8. Rosa TLM et al. Food Res Int. 2020 Nov;137:109383.

9. Demoliner F et al. Food Res Int. 2018 Oct;112:434-442.

10. Vieira ME et al. Acta Biochim Biophys Sin (Shanghai). 2015 Sep;47(9):716-729.

11. Hertel Pereira AC et al. J Cosmet Sci. 2021 Mar-Apr;72(2):155-162.

Editor’s note: This article is adapted from an explanatory statement that Dr. Feldman wrote for the Coalition of State Rheumatology Organizations (CSRO).

According to the Guinness Book of World records, the longest time someone has held their breath underwater voluntarily is 24 minutes and 37.36 seconds. While certainly an amazing feat, UnitedHealthcare, many of the Blues, and other national “payers” are expecting rheumatologists and other specialists to live “underwater” in order to take care of their patients. In other words, these insurance companies are mandating that specialists use certain provider-administered biosimilars whose acquisition cost is higher than what the insurance company is willing to reimburse them. Essentially, the insurance companies expect the rheumatologists to pay them to take care of their patients. Because of the substantial and destabilizing financial losses incurred, many practices and free-standing infusion centers have been forced to cease offering these biosimilars. Most rheumatologists will provide patients with appropriate alternatives when available and permitted by the insurer; otherwise, they must refer patients to hospital-based infusion centers. That results in delayed care and increased costs for patients and the system, because hospital-based infusion typically costs more than twice what office-based infusion costs.

Quantifying the Problem

To help quantify the magnitude of this issue, the Coalition of State Rheumatology Organizations (CSRO) recently conducted a survey of its membership. A shocking 97% of respondents reported that their practice had been affected by reimbursement rates for some biosimilars being lower than acquisition costs, with 91% of respondents stating that this issue is more pronounced for certain biosimilars than others. Across the board, respondents most frequently identified Inflectra (infliximab-dyyb) and Avsola (infliximab-axxq) as being especially affected: Over 88% and over 85% of respondents identified these two products, respectively, as being underwater. These results support the ongoing anecdotal reports CSRO continues to receive from rheumatology practices.

However, the survey results indicated that this issue is by no means confined to those two biosimilars. Truxima (rituximab-abbs) — a biosimilar for Rituxan — was frequently mentioned as well. Notably, respondents almost uniformly identified biosimilars in the infliximab and rituximab families, which illustrates that this issue is no longer confined to one or two early-to-market biosimilars but has almost become a hallmark of this particular biosimilars market. Remarkably, one respondent commented that the brand products are now cheaper to acquire than the biosimilars. Furthermore, the survey included respondents from across the country, indicating that this issue is not confined to a particular region.
 

How Did This Happen?

Biosimilars held promise for increasing availability and decreasing biologic costs for patients but, thus far, no patients have seen their cost go down. It appears that the only biosimilars that have made it to “preferred” status on the formulary are the ones that have made more money for the middlemen in the drug supply chain, particularly those that construct formularies. Now, we have provider-administered biosimilars whose acquisition cost exceeds the reimbursement for these drugs. This disparity was ultimately created by biosimilar manufacturers “over-rebating” their drugs to health insurance companies to gain “fail-first” status on the formulary.

For example, the manufacturer of Inflectra offered substantial rebates to health insurers for preferred formulary placement. These rebates are factored into the sales price of the medication, which then results in a rapidly declining average sales price (ASP) for the biosimilar. Unfortunately, the acquisition cost for the drug does not experience commensurate reductions, resulting in physicians being reimbursed far less for the drug than it costs to acquire. The financial losses for physicians put them underwater as a result of the acquisition costs for the preferred drugs far surpassing the reimbursement from the health insurance company that constructed the formulary.

While various factors affect ASPs and acquisition costs, this particular consequence of formulary placement based on price concessions is a major driver of the underwater situation in which physicians have found themselves with many biosimilars. Not only does that lead to a lower uptake of biosimilars, but it also results in patients being referred to the hospital outpatient infusion sites to receive this care, as freestanding infusion centers cannot treat these patients either. Hospitals incur higher costs because of facility fees and elevated rates, and this makes private rheumatology in-office infusion centers a much lower-cost option. Similarly, home infusion services, while convenient, are marginally more expensive than private practices and, in cases of biologic infusions, it is important to note that physicians’ offices have a greater safety profile than home infusion of biologics. The overall result of these “fail-first underwater drugs” is delayed and more costly care for the patient and the “system,” particularly self-insured employers.
 

What Is Being Done to Correct This?

Since ASPs are updated quarterly, it is possible that acquisition costs and reimbursements might stabilize over time, making the drugs affordable again to practices. However, that does not appear to be happening in the near future, so that possibility does not offer immediate relief to struggling practices. It doesn’t promise a favorable outlook for future biosimilar entries of provider-administered medications if formularies continue to prefer the highest-rebated medication.

This dynamic between ASP and acquisition cost does not happen on the pharmacy side because the price concessions on specific drug rebates and fees are proprietary. There appears to be no equivalent to a publicly known ASP on the pharmacy side, which has led to myriad pricing definitions and manipulation on the pharmacy benefit side of medications. In any event, the savings from rebates and other manufacturer price concessions on pharmacy drugs do not influence ASPs of medical benefit drugs.

The Inflation Reduction Act provided a temporary increase in the add-on payment for biosimilars from ASP+6% to ASP+8%, but as long as the biosimilar’s ASP is lower than the reference brand’s ASP, that temporary increase does not appear to make up for the large differential between ASP and acquisition cost. It should be noted that any federal attempt to artificially lower the ASP of a provider-administered drug without a pathway assuring that the acquisition cost for the provider is less than the reimbursement is going to result in loss of access for patients to those medications and/or higher hospital site of care costs.
 

A Few Partial Fixes, But Most Complaints Go Ignored

Considering the higher costs of hospital-based infusion, insurers should be motivated to keep patients within private practices. Perhaps through insurers’ recognition of that fact, some practices have successfully negotiated exceptions for specific patients by discussing this situation with insurers. From the feedback that CSRO has received from rheumatology practices, it appears that most insurers have been ignoring the complaints from physicians. The few who have responded have resulted in only partial fixes, with some of the biosimilars still left underwater.

Ultimate Solution?

This issue is a direct result of the “rebate game,” whereby price concessions from drug manufacturers drive formulary placement. For provider-administered medications, this results in an artificially lowered ASP, not as a consequence of free-market incentives that benefit the patient, but as a result of misaligned incentives created by Safe Harbor–protected “kickbacks,” distorting the free market and paradoxically reducing access to these medications, delaying care, and increasing prices for patients and the healthcare system.

While federal and state governments are not likely to address this particular situation in the biosimilars market, CSRO is highlighting this issue as a prime example of why the current formulary construction system urgently requires federal reform. At this time, the biosimilars most affected are Inflectra and Avsola, but if nothing changes, more and more biosimilars will fall victim to the short-sighted pricing strategy of aggressive rebating to gain formulary position, with physician purchasers and patients left to navigate the aftermath. The existing system, which necessitates drug companies purchasing formulary access from pharmacy benefit managers, has led to delayed and even denied patient access to certain provider-administered drugs. Moreover, it now appears to be hindering the adoption of biosimilars.

To address this, a multifaceted approach is required. It not only involves reevaluating the rebate system and its impact on formulary construction and ASP, but also ensuring that acquisition costs for providers are aligned with reimbursement rates. Insurers must recognize the economic and clinical value of maintaining infusions within private practices and immediately update their policies to ensure that physician in-office infusion is financially feasible for these “fail-first” biosimilars.

Ultimately, the goal should be to create a sustainable model that promotes the use of affordable biosimilars, enhances patient access to affordable care, and supports the financial viability of medical practices. Concerted efforts to reform the current formulary construction system are required to achieve a healthcare environment that is both cost effective and patient centric.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Editor’s note: This article is adapted from an explanatory statement that Dr. Feldman wrote for the Coalition of State Rheumatology Organizations (CSRO).

According to the Guinness Book of World records, the longest time someone has held their breath underwater voluntarily is 24 minutes and 37.36 seconds. While certainly an amazing feat, UnitedHealthcare, many of the Blues, and other national “payers” are expecting rheumatologists and other specialists to live “underwater” in order to take care of their patients. In other words, these insurance companies are mandating that specialists use certain provider-administered biosimilars whose acquisition cost is higher than what the insurance company is willing to reimburse them. Essentially, the insurance companies expect the rheumatologists to pay them to take care of their patients. Because of the substantial and destabilizing financial losses incurred, many practices and free-standing infusion centers have been forced to cease offering these biosimilars. Most rheumatologists will provide patients with appropriate alternatives when available and permitted by the insurer; otherwise, they must refer patients to hospital-based infusion centers. That results in delayed care and increased costs for patients and the system, because hospital-based infusion typically costs more than twice what office-based infusion costs.

Quantifying the Problem

To help quantify the magnitude of this issue, the Coalition of State Rheumatology Organizations (CSRO) recently conducted a survey of its membership. A shocking 97% of respondents reported that their practice had been affected by reimbursement rates for some biosimilars being lower than acquisition costs, with 91% of respondents stating that this issue is more pronounced for certain biosimilars than others. Across the board, respondents most frequently identified Inflectra (infliximab-dyyb) and Avsola (infliximab-axxq) as being especially affected: Over 88% and over 85% of respondents identified these two products, respectively, as being underwater. These results support the ongoing anecdotal reports CSRO continues to receive from rheumatology practices.

However, the survey results indicated that this issue is by no means confined to those two biosimilars. Truxima (rituximab-abbs) — a biosimilar for Rituxan — was frequently mentioned as well. Notably, respondents almost uniformly identified biosimilars in the infliximab and rituximab families, which illustrates that this issue is no longer confined to one or two early-to-market biosimilars but has almost become a hallmark of this particular biosimilars market. Remarkably, one respondent commented that the brand products are now cheaper to acquire than the biosimilars. Furthermore, the survey included respondents from across the country, indicating that this issue is not confined to a particular region.
 

How Did This Happen?

Biosimilars held promise for increasing availability and decreasing biologic costs for patients but, thus far, no patients have seen their cost go down. It appears that the only biosimilars that have made it to “preferred” status on the formulary are the ones that have made more money for the middlemen in the drug supply chain, particularly those that construct formularies. Now, we have provider-administered biosimilars whose acquisition cost exceeds the reimbursement for these drugs. This disparity was ultimately created by biosimilar manufacturers “over-rebating” their drugs to health insurance companies to gain “fail-first” status on the formulary.

For example, the manufacturer of Inflectra offered substantial rebates to health insurers for preferred formulary placement. These rebates are factored into the sales price of the medication, which then results in a rapidly declining average sales price (ASP) for the biosimilar. Unfortunately, the acquisition cost for the drug does not experience commensurate reductions, resulting in physicians being reimbursed far less for the drug than it costs to acquire. The financial losses for physicians put them underwater as a result of the acquisition costs for the preferred drugs far surpassing the reimbursement from the health insurance company that constructed the formulary.

While various factors affect ASPs and acquisition costs, this particular consequence of formulary placement based on price concessions is a major driver of the underwater situation in which physicians have found themselves with many biosimilars. Not only does that lead to a lower uptake of biosimilars, but it also results in patients being referred to the hospital outpatient infusion sites to receive this care, as freestanding infusion centers cannot treat these patients either. Hospitals incur higher costs because of facility fees and elevated rates, and this makes private rheumatology in-office infusion centers a much lower-cost option. Similarly, home infusion services, while convenient, are marginally more expensive than private practices and, in cases of biologic infusions, it is important to note that physicians’ offices have a greater safety profile than home infusion of biologics. The overall result of these “fail-first underwater drugs” is delayed and more costly care for the patient and the “system,” particularly self-insured employers.
 

What Is Being Done to Correct This?

Since ASPs are updated quarterly, it is possible that acquisition costs and reimbursements might stabilize over time, making the drugs affordable again to practices. However, that does not appear to be happening in the near future, so that possibility does not offer immediate relief to struggling practices. It doesn’t promise a favorable outlook for future biosimilar entries of provider-administered medications if formularies continue to prefer the highest-rebated medication.

This dynamic between ASP and acquisition cost does not happen on the pharmacy side because the price concessions on specific drug rebates and fees are proprietary. There appears to be no equivalent to a publicly known ASP on the pharmacy side, which has led to myriad pricing definitions and manipulation on the pharmacy benefit side of medications. In any event, the savings from rebates and other manufacturer price concessions on pharmacy drugs do not influence ASPs of medical benefit drugs.

The Inflation Reduction Act provided a temporary increase in the add-on payment for biosimilars from ASP+6% to ASP+8%, but as long as the biosimilar’s ASP is lower than the reference brand’s ASP, that temporary increase does not appear to make up for the large differential between ASP and acquisition cost. It should be noted that any federal attempt to artificially lower the ASP of a provider-administered drug without a pathway assuring that the acquisition cost for the provider is less than the reimbursement is going to result in loss of access for patients to those medications and/or higher hospital site of care costs.
 

A Few Partial Fixes, But Most Complaints Go Ignored

Considering the higher costs of hospital-based infusion, insurers should be motivated to keep patients within private practices. Perhaps through insurers’ recognition of that fact, some practices have successfully negotiated exceptions for specific patients by discussing this situation with insurers. From the feedback that CSRO has received from rheumatology practices, it appears that most insurers have been ignoring the complaints from physicians. The few who have responded have resulted in only partial fixes, with some of the biosimilars still left underwater.

Ultimate Solution?

This issue is a direct result of the “rebate game,” whereby price concessions from drug manufacturers drive formulary placement. For provider-administered medications, this results in an artificially lowered ASP, not as a consequence of free-market incentives that benefit the patient, but as a result of misaligned incentives created by Safe Harbor–protected “kickbacks,” distorting the free market and paradoxically reducing access to these medications, delaying care, and increasing prices for patients and the healthcare system.

While federal and state governments are not likely to address this particular situation in the biosimilars market, CSRO is highlighting this issue as a prime example of why the current formulary construction system urgently requires federal reform. At this time, the biosimilars most affected are Inflectra and Avsola, but if nothing changes, more and more biosimilars will fall victim to the short-sighted pricing strategy of aggressive rebating to gain formulary position, with physician purchasers and patients left to navigate the aftermath. The existing system, which necessitates drug companies purchasing formulary access from pharmacy benefit managers, has led to delayed and even denied patient access to certain provider-administered drugs. Moreover, it now appears to be hindering the adoption of biosimilars.

To address this, a multifaceted approach is required. It not only involves reevaluating the rebate system and its impact on formulary construction and ASP, but also ensuring that acquisition costs for providers are aligned with reimbursement rates. Insurers must recognize the economic and clinical value of maintaining infusions within private practices and immediately update their policies to ensure that physician in-office infusion is financially feasible for these “fail-first” biosimilars.

Ultimately, the goal should be to create a sustainable model that promotes the use of affordable biosimilars, enhances patient access to affordable care, and supports the financial viability of medical practices. Concerted efforts to reform the current formulary construction system are required to achieve a healthcare environment that is both cost effective and patient centric.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Editor’s note: This article is adapted from an explanatory statement that Dr. Feldman wrote for the Coalition of State Rheumatology Organizations (CSRO).

According to the Guinness Book of World records, the longest time someone has held their breath underwater voluntarily is 24 minutes and 37.36 seconds. While certainly an amazing feat, UnitedHealthcare, many of the Blues, and other national “payers” are expecting rheumatologists and other specialists to live “underwater” in order to take care of their patients. In other words, these insurance companies are mandating that specialists use certain provider-administered biosimilars whose acquisition cost is higher than what the insurance company is willing to reimburse them. Essentially, the insurance companies expect the rheumatologists to pay them to take care of their patients. Because of the substantial and destabilizing financial losses incurred, many practices and free-standing infusion centers have been forced to cease offering these biosimilars. Most rheumatologists will provide patients with appropriate alternatives when available and permitted by the insurer; otherwise, they must refer patients to hospital-based infusion centers. That results in delayed care and increased costs for patients and the system, because hospital-based infusion typically costs more than twice what office-based infusion costs.

Quantifying the Problem

To help quantify the magnitude of this issue, the Coalition of State Rheumatology Organizations (CSRO) recently conducted a survey of its membership. A shocking 97% of respondents reported that their practice had been affected by reimbursement rates for some biosimilars being lower than acquisition costs, with 91% of respondents stating that this issue is more pronounced for certain biosimilars than others. Across the board, respondents most frequently identified Inflectra (infliximab-dyyb) and Avsola (infliximab-axxq) as being especially affected: Over 88% and over 85% of respondents identified these two products, respectively, as being underwater. These results support the ongoing anecdotal reports CSRO continues to receive from rheumatology practices.

However, the survey results indicated that this issue is by no means confined to those two biosimilars. Truxima (rituximab-abbs) — a biosimilar for Rituxan — was frequently mentioned as well. Notably, respondents almost uniformly identified biosimilars in the infliximab and rituximab families, which illustrates that this issue is no longer confined to one or two early-to-market biosimilars but has almost become a hallmark of this particular biosimilars market. Remarkably, one respondent commented that the brand products are now cheaper to acquire than the biosimilars. Furthermore, the survey included respondents from across the country, indicating that this issue is not confined to a particular region.
 

How Did This Happen?

Biosimilars held promise for increasing availability and decreasing biologic costs for patients but, thus far, no patients have seen their cost go down. It appears that the only biosimilars that have made it to “preferred” status on the formulary are the ones that have made more money for the middlemen in the drug supply chain, particularly those that construct formularies. Now, we have provider-administered biosimilars whose acquisition cost exceeds the reimbursement for these drugs. This disparity was ultimately created by biosimilar manufacturers “over-rebating” their drugs to health insurance companies to gain “fail-first” status on the formulary.

For example, the manufacturer of Inflectra offered substantial rebates to health insurers for preferred formulary placement. These rebates are factored into the sales price of the medication, which then results in a rapidly declining average sales price (ASP) for the biosimilar. Unfortunately, the acquisition cost for the drug does not experience commensurate reductions, resulting in physicians being reimbursed far less for the drug than it costs to acquire. The financial losses for physicians put them underwater as a result of the acquisition costs for the preferred drugs far surpassing the reimbursement from the health insurance company that constructed the formulary.

While various factors affect ASPs and acquisition costs, this particular consequence of formulary placement based on price concessions is a major driver of the underwater situation in which physicians have found themselves with many biosimilars. Not only does that lead to a lower uptake of biosimilars, but it also results in patients being referred to the hospital outpatient infusion sites to receive this care, as freestanding infusion centers cannot treat these patients either. Hospitals incur higher costs because of facility fees and elevated rates, and this makes private rheumatology in-office infusion centers a much lower-cost option. Similarly, home infusion services, while convenient, are marginally more expensive than private practices and, in cases of biologic infusions, it is important to note that physicians’ offices have a greater safety profile than home infusion of biologics. The overall result of these “fail-first underwater drugs” is delayed and more costly care for the patient and the “system,” particularly self-insured employers.
 

What Is Being Done to Correct This?

Since ASPs are updated quarterly, it is possible that acquisition costs and reimbursements might stabilize over time, making the drugs affordable again to practices. However, that does not appear to be happening in the near future, so that possibility does not offer immediate relief to struggling practices. It doesn’t promise a favorable outlook for future biosimilar entries of provider-administered medications if formularies continue to prefer the highest-rebated medication.

This dynamic between ASP and acquisition cost does not happen on the pharmacy side because the price concessions on specific drug rebates and fees are proprietary. There appears to be no equivalent to a publicly known ASP on the pharmacy side, which has led to myriad pricing definitions and manipulation on the pharmacy benefit side of medications. In any event, the savings from rebates and other manufacturer price concessions on pharmacy drugs do not influence ASPs of medical benefit drugs.

The Inflation Reduction Act provided a temporary increase in the add-on payment for biosimilars from ASP+6% to ASP+8%, but as long as the biosimilar’s ASP is lower than the reference brand’s ASP, that temporary increase does not appear to make up for the large differential between ASP and acquisition cost. It should be noted that any federal attempt to artificially lower the ASP of a provider-administered drug without a pathway assuring that the acquisition cost for the provider is less than the reimbursement is going to result in loss of access for patients to those medications and/or higher hospital site of care costs.
 

A Few Partial Fixes, But Most Complaints Go Ignored

Considering the higher costs of hospital-based infusion, insurers should be motivated to keep patients within private practices. Perhaps through insurers’ recognition of that fact, some practices have successfully negotiated exceptions for specific patients by discussing this situation with insurers. From the feedback that CSRO has received from rheumatology practices, it appears that most insurers have been ignoring the complaints from physicians. The few who have responded have resulted in only partial fixes, with some of the biosimilars still left underwater.

Ultimate Solution?

This issue is a direct result of the “rebate game,” whereby price concessions from drug manufacturers drive formulary placement. For provider-administered medications, this results in an artificially lowered ASP, not as a consequence of free-market incentives that benefit the patient, but as a result of misaligned incentives created by Safe Harbor–protected “kickbacks,” distorting the free market and paradoxically reducing access to these medications, delaying care, and increasing prices for patients and the healthcare system.

While federal and state governments are not likely to address this particular situation in the biosimilars market, CSRO is highlighting this issue as a prime example of why the current formulary construction system urgently requires federal reform. At this time, the biosimilars most affected are Inflectra and Avsola, but if nothing changes, more and more biosimilars will fall victim to the short-sighted pricing strategy of aggressive rebating to gain formulary position, with physician purchasers and patients left to navigate the aftermath. The existing system, which necessitates drug companies purchasing formulary access from pharmacy benefit managers, has led to delayed and even denied patient access to certain provider-administered drugs. Moreover, it now appears to be hindering the adoption of biosimilars.

To address this, a multifaceted approach is required. It not only involves reevaluating the rebate system and its impact on formulary construction and ASP, but also ensuring that acquisition costs for providers are aligned with reimbursement rates. Insurers must recognize the economic and clinical value of maintaining infusions within private practices and immediately update their policies to ensure that physician in-office infusion is financially feasible for these “fail-first” biosimilars.

Ultimately, the goal should be to create a sustainable model that promotes the use of affordable biosimilars, enhances patient access to affordable care, and supports the financial viability of medical practices. Concerted efforts to reform the current formulary construction system are required to achieve a healthcare environment that is both cost effective and patient centric.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.

One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.

While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.

Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.

Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. The best-performing chatbot in Mr. Chen and colleagues’ study, Claude AI, performed significantly higher than the Reddit physicians on all the domains evaluated: quality, empathy, and readability.
 

Q&A With Author of New Research

Mr. Chen discussed his new study’s implications during an interview with this news organization.

Question: What is novel about this study?

Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.



Question: Why would chatbot responses seem more empathetic than those of physicians?

Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.



Question: Do chatbots just seem empathetic because they are chattier?

Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.



Question: How were quality and empathy measured by the reviewers?

Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.

Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.

With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.

Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’



Question: Why would physicians, not patients, be the best evaluators of empathy?

Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.



Question: Should cancer patients go ahead and consult chatbots?

Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.

Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.

This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.

This Q&A was edited for clarity.

Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.

One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.

While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.

Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.

Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. The best-performing chatbot in Mr. Chen and colleagues’ study, Claude AI, performed significantly higher than the Reddit physicians on all the domains evaluated: quality, empathy, and readability.
 

Q&A With Author of New Research

Mr. Chen discussed his new study’s implications during an interview with this news organization.

Question: What is novel about this study?

Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.



Question: Why would chatbot responses seem more empathetic than those of physicians?

Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.



Question: Do chatbots just seem empathetic because they are chattier?

Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.



Question: How were quality and empathy measured by the reviewers?

Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.

Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.

With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.

Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’



Question: Why would physicians, not patients, be the best evaluators of empathy?

Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.



Question: Should cancer patients go ahead and consult chatbots?

Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.

Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.

This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.

This Q&A was edited for clarity.

Large language models (LLM) such as ChatGPT have shown mixed results in the quality of their responses to consumer questions about cancer.

One recent study found AI chatbots to churn out incomplete, inaccurate, or even nonsensical cancer treatment recommendations, while another found them to generate largely accurate — if technical — responses to the most common cancer questions.

While researchers have seen success with purpose-built chatbots created to address patient concerns about specific cancers, the consensus to date has been that the generalized models like ChatGPT remain works in progress and that physicians should avoid pointing patients to them, for now.

Yet new findings suggest that these chatbots may do better than individual physicians, at least on some measures, when it comes to answering queries about cancer. For research published May 16 in JAMA Oncology (doi: 10.1001/jamaoncol.2024.0836), David Chen, a medical student at the University of Toronto, and his colleagues, isolated a random sample of 200 questions related to cancer care addressed to doctors on the public online forum Reddit. They then compared responses from oncologists with responses generated by three different AI chatbots. The blinded responses were rated for quality, readability, and empathy by six physicians, including oncologists and palliative and supportive care specialists.

Mr. Chen and colleagues’ research was modeled after a 2023 study that measured the quality of physician responses compared with chatbots for general medicine questions addressed to doctors on Reddit. That study found that the chatbots produced more empathetic-sounding answers, something Mr. Chen’s study also found. The best-performing chatbot in Mr. Chen and colleagues’ study, Claude AI, performed significantly higher than the Reddit physicians on all the domains evaluated: quality, empathy, and readability.
 

Q&A With Author of New Research

Mr. Chen discussed his new study’s implications during an interview with this news organization.

Question: What is novel about this study?

Mr. Chen: We’ve seen many evaluations of chatbots that test for medical accuracy, but this study occurs in the domain of oncology care, where there are unique psychosocial and emotional considerations that are not precisely reflected in a general medicine setting. In effect, this study is putting these chatbots through a harder challenge.



Question: Why would chatbot responses seem more empathetic than those of physicians?

Mr. Chen: With the physician responses that we observed in our sample data set, we saw that there was very high variation of amount of apparent effort [in the physician responses]. Some physicians would put in a lot of time and effort, thinking through their response, and others wouldn’t do so as much. These chatbots don’t face fatigue the way humans do, or burnout. So they’re able to consistently provide responses with less variation in empathy.



Question: Do chatbots just seem empathetic because they are chattier?

Mr. Chen: We did think of verbosity as a potential confounder in this study. So we set a word count limit for the chatbot responses to keep it in the range of the physician responses. That way, verbosity was no longer a significant factor.



Question: How were quality and empathy measured by the reviewers?

Mr. Chen: For our study we used two teams of readers, each team composed of three physicians. In terms of the actual metrics we used, they were pilot metrics. There are no well-defined measurement scales or checklists that we could use to measure empathy. This is an emerging field of research. So we came up by consensus with our own set of ratings, and we feel that this is an area for the research to define a standardized set of guidelines.

Another novel aspect of this study is that we separated out different dimensions of quality and empathy. A quality response didn’t just mean it was medically accurate — quality also had to do with the focus and completeness of the response.

With empathy there are cognitive and emotional dimensions. Cognitive empathy uses critical thinking to understand the person’s emotions and thoughts and then adjusting a response to fit that. A patient may not want the best medically indicated treatment for their condition, because they want to preserve their quality of life. The chatbot may be able to adjust its recommendation with consideration of some of those humanistic elements that the patient is presenting with.

Emotional empathy is more about being supportive of the patient’s emotions by using expressions like ‘I understand where you’re coming from.’ or, ‘I can see how that makes you feel.’



Question: Why would physicians, not patients, be the best evaluators of empathy?

Mr. Chen: We’re actually very interested in evaluating patient ratings of empathy. We are conducting a follow-up study that evaluates patient ratings of empathy to the same set of chatbot and physician responses,to see if there are differences.



Question: Should cancer patients go ahead and consult chatbots?

Mr. Chen: Although we did observe increases in all of the metrics compared with physicians, this is a very specialized evaluation scenario where we’re using these Reddit questions and responses.

Naturally, we would need to do a trial, a head to head randomized comparison of physicians versus chatbots.

This pilot study does highlight the promising potential of these chatbots to suggest responses. But we can’t fully recommend that they should be used as standalone clinical tools without physicians.

This Q&A was edited for clarity.

In an experiment that pitted the wits of pediatric dermatologists against ChatGPT versions 3.5 and 4.0 to answer board examination–type questions, pediatric dermatologists outperformed both iterations of the artificial intelligence (AI)–based tool, results from a small single-center study showed.

“We were relieved to find that the pediatric dermatologists in our study performed better than ChatGPT on both multiple choice and case-based questions; however, the latest iteration of ChatGPT (4.0) was very close,” one of the study’s first authors Charles Huang, a fourth-year medical student at Thomas Jefferson University, Philadelphia, said in an interview. “Something else that was interesting in our data was that the pediatric dermatologists performed much better than ChatGPT on questions related to procedural dermatology/surgical techniques, perhaps indicating that knowledge/reasoning gained through practical experience isn’t easily replicated in AI tools such as ChatGPT.”

Charles Huang

For the study, which was published on May 9 in Pediatric Dermatology, Mr. Huang, and co-first author Esther Zhang, BS, a medical student at the University of Pennsylvania, Philadelphia, and coauthors from the Department of Dermatology, Children’s Hospital of Philadelphia, asked five pediatric dermatologists to answer 24 text-based questions including 16 single-answer, multiple-choice questions and two multiple answer questions drawn from the American Board of Dermatology 2021 Certification Sample Test and six free-response case-based questions drawn from the “Photoquiz” section of Pediatric Dermatology between July 2022 and July 2023. The researchers then processed the same set of questions through ChatGPT versions 3.5 and 4.0 and used statistical analysis to compare responses between the pediatric dermatologists and ChatGPT. A 5-point scale adapted from current AI tools was used to score replies to case-based questions.

On average, study participants had 5.6 years of clinical experience. Pediatric dermatologists performed significantly better than ChatGPT version 3.5 on multiple-choice and multiple answer questions (91.4% vs 76.2%, respectively; P = .021) but not significantly better than ChatGPT version 4.0 (90.5%; P = .44). As for replies to case-based questions, the average performance based on the 5-point scale was 3.81 for pediatric dermatologists and 3.53 for ChatGPT overall. The mean scores were significantly greater for pediatric dermatologists than for ChatGPT version 3.5 (P = .039) but not ChatGPT version 4.0 (P = .43).

The researchers acknowledged certain limitations of the analysis, including the evolving nature of AI tools, which may affect the reproducibility of results with subsequent model updates. And, while participating pediatric dermatologists said they were unfamiliar with the questions and cases used in the study, “there is potential for prior exposure through other dermatology board examination review processes,” they wrote.

“AI tools such as ChatGPT and similar large language models can be a valuable tool in your clinical practice, but be aware of potential pitfalls such as patient privacy, medical inaccuracies, [and] intrinsic biases in the tools,” Mr. Huang told this news organization. “As these technologies continue to advance, it is essential for all of us as medical clinicians to gain familiarity and stay abreast of new developments, just as we adapted to electronic health records and the use of the Internet.”

Maria Buethe, MD, PhD, a pediatric dermatology fellow at Rady Children’s Hospital–San Diego, who was asked to comment on the study, said she found it “interesting” that ChatGPT’s version 4.0 started to produce comparable results to clinician responses in some of the tested scenarios.

Dr. Buethe

“The authors propose a set of best practices for pediatric dermatology clinicians using ChatGPT and other AI tools,” said Dr. Buethe, who was senior author of a recent literature review on AI and its application to pediatric dermatology. It was published in SKIN The Journal of Cutaneous Medicine. “One interesting recommended use for AI tools is to utilize it to generate differential diagnosis, which can broaden the list of pathologies previously considered.”

Asked to comment on the study, Erum Ilyas, MD, who practices dermatology in King of Prussia, Pennsylvania, and is a member of the Society for Pediatric Dermatology, said she was not surprised that ChatGPT “can perform fairly well on multiple-choice questions as we find available in testing circumstances,” as presented in the study. “Just as board questions only support testing a base of medical knowledge and facts for clinicians to master, they do not necessarily provide real-life circumstances that apply to caring for patients, which is inherently nuanced.”

Dr. Ilyas

A version of this article appeared on Medscape.com .

In an experiment that pitted the wits of pediatric dermatologists against ChatGPT versions 3.5 and 4.0 to answer board examination–type questions, pediatric dermatologists outperformed both iterations of the artificial intelligence (AI)–based tool, results from a small single-center study showed.

“We were relieved to find that the pediatric dermatologists in our study performed better than ChatGPT on both multiple choice and case-based questions; however, the latest iteration of ChatGPT (4.0) was very close,” one of the study’s first authors Charles Huang, a fourth-year medical student at Thomas Jefferson University, Philadelphia, said in an interview. “Something else that was interesting in our data was that the pediatric dermatologists performed much better than ChatGPT on questions related to procedural dermatology/surgical techniques, perhaps indicating that knowledge/reasoning gained through practical experience isn’t easily replicated in AI tools such as ChatGPT.”

Charles Huang

For the study, which was published on May 9 in Pediatric Dermatology, Mr. Huang, and co-first author Esther Zhang, BS, a medical student at the University of Pennsylvania, Philadelphia, and coauthors from the Department of Dermatology, Children’s Hospital of Philadelphia, asked five pediatric dermatologists to answer 24 text-based questions including 16 single-answer, multiple-choice questions and two multiple answer questions drawn from the American Board of Dermatology 2021 Certification Sample Test and six free-response case-based questions drawn from the “Photoquiz” section of Pediatric Dermatology between July 2022 and July 2023. The researchers then processed the same set of questions through ChatGPT versions 3.5 and 4.0 and used statistical analysis to compare responses between the pediatric dermatologists and ChatGPT. A 5-point scale adapted from current AI tools was used to score replies to case-based questions.

On average, study participants had 5.6 years of clinical experience. Pediatric dermatologists performed significantly better than ChatGPT version 3.5 on multiple-choice and multiple answer questions (91.4% vs 76.2%, respectively; P = .021) but not significantly better than ChatGPT version 4.0 (90.5%; P = .44). As for replies to case-based questions, the average performance based on the 5-point scale was 3.81 for pediatric dermatologists and 3.53 for ChatGPT overall. The mean scores were significantly greater for pediatric dermatologists than for ChatGPT version 3.5 (P = .039) but not ChatGPT version 4.0 (P = .43).

The researchers acknowledged certain limitations of the analysis, including the evolving nature of AI tools, which may affect the reproducibility of results with subsequent model updates. And, while participating pediatric dermatologists said they were unfamiliar with the questions and cases used in the study, “there is potential for prior exposure through other dermatology board examination review processes,” they wrote.

“AI tools such as ChatGPT and similar large language models can be a valuable tool in your clinical practice, but be aware of potential pitfalls such as patient privacy, medical inaccuracies, [and] intrinsic biases in the tools,” Mr. Huang told this news organization. “As these technologies continue to advance, it is essential for all of us as medical clinicians to gain familiarity and stay abreast of new developments, just as we adapted to electronic health records and the use of the Internet.”

Maria Buethe, MD, PhD, a pediatric dermatology fellow at Rady Children’s Hospital–San Diego, who was asked to comment on the study, said she found it “interesting” that ChatGPT’s version 4.0 started to produce comparable results to clinician responses in some of the tested scenarios.

Dr. Buethe

“The authors propose a set of best practices for pediatric dermatology clinicians using ChatGPT and other AI tools,” said Dr. Buethe, who was senior author of a recent literature review on AI and its application to pediatric dermatology. It was published in SKIN The Journal of Cutaneous Medicine. “One interesting recommended use for AI tools is to utilize it to generate differential diagnosis, which can broaden the list of pathologies previously considered.”

Asked to comment on the study, Erum Ilyas, MD, who practices dermatology in King of Prussia, Pennsylvania, and is a member of the Society for Pediatric Dermatology, said she was not surprised that ChatGPT “can perform fairly well on multiple-choice questions as we find available in testing circumstances,” as presented in the study. “Just as board questions only support testing a base of medical knowledge and facts for clinicians to master, they do not necessarily provide real-life circumstances that apply to caring for patients, which is inherently nuanced.”

Dr. Ilyas

A version of this article appeared on Medscape.com .

In an experiment that pitted the wits of pediatric dermatologists against ChatGPT versions 3.5 and 4.0 to answer board examination–type questions, pediatric dermatologists outperformed both iterations of the artificial intelligence (AI)–based tool, results from a small single-center study showed.

“We were relieved to find that the pediatric dermatologists in our study performed better than ChatGPT on both multiple choice and case-based questions; however, the latest iteration of ChatGPT (4.0) was very close,” one of the study’s first authors Charles Huang, a fourth-year medical student at Thomas Jefferson University, Philadelphia, said in an interview. “Something else that was interesting in our data was that the pediatric dermatologists performed much better than ChatGPT on questions related to procedural dermatology/surgical techniques, perhaps indicating that knowledge/reasoning gained through practical experience isn’t easily replicated in AI tools such as ChatGPT.”

Charles Huang

For the study, which was published on May 9 in Pediatric Dermatology, Mr. Huang, and co-first author Esther Zhang, BS, a medical student at the University of Pennsylvania, Philadelphia, and coauthors from the Department of Dermatology, Children’s Hospital of Philadelphia, asked five pediatric dermatologists to answer 24 text-based questions including 16 single-answer, multiple-choice questions and two multiple answer questions drawn from the American Board of Dermatology 2021 Certification Sample Test and six free-response case-based questions drawn from the “Photoquiz” section of Pediatric Dermatology between July 2022 and July 2023. The researchers then processed the same set of questions through ChatGPT versions 3.5 and 4.0 and used statistical analysis to compare responses between the pediatric dermatologists and ChatGPT. A 5-point scale adapted from current AI tools was used to score replies to case-based questions.

On average, study participants had 5.6 years of clinical experience. Pediatric dermatologists performed significantly better than ChatGPT version 3.5 on multiple-choice and multiple answer questions (91.4% vs 76.2%, respectively; P = .021) but not significantly better than ChatGPT version 4.0 (90.5%; P = .44). As for replies to case-based questions, the average performance based on the 5-point scale was 3.81 for pediatric dermatologists and 3.53 for ChatGPT overall. The mean scores were significantly greater for pediatric dermatologists than for ChatGPT version 3.5 (P = .039) but not ChatGPT version 4.0 (P = .43).

The researchers acknowledged certain limitations of the analysis, including the evolving nature of AI tools, which may affect the reproducibility of results with subsequent model updates. And, while participating pediatric dermatologists said they were unfamiliar with the questions and cases used in the study, “there is potential for prior exposure through other dermatology board examination review processes,” they wrote.

“AI tools such as ChatGPT and similar large language models can be a valuable tool in your clinical practice, but be aware of potential pitfalls such as patient privacy, medical inaccuracies, [and] intrinsic biases in the tools,” Mr. Huang told this news organization. “As these technologies continue to advance, it is essential for all of us as medical clinicians to gain familiarity and stay abreast of new developments, just as we adapted to electronic health records and the use of the Internet.”

Maria Buethe, MD, PhD, a pediatric dermatology fellow at Rady Children’s Hospital–San Diego, who was asked to comment on the study, said she found it “interesting” that ChatGPT’s version 4.0 started to produce comparable results to clinician responses in some of the tested scenarios.

Dr. Buethe

“The authors propose a set of best practices for pediatric dermatology clinicians using ChatGPT and other AI tools,” said Dr. Buethe, who was senior author of a recent literature review on AI and its application to pediatric dermatology. It was published in SKIN The Journal of Cutaneous Medicine. “One interesting recommended use for AI tools is to utilize it to generate differential diagnosis, which can broaden the list of pathologies previously considered.”

Asked to comment on the study, Erum Ilyas, MD, who practices dermatology in King of Prussia, Pennsylvania, and is a member of the Society for Pediatric Dermatology, said she was not surprised that ChatGPT “can perform fairly well on multiple-choice questions as we find available in testing circumstances,” as presented in the study. “Just as board questions only support testing a base of medical knowledge and facts for clinicians to master, they do not necessarily provide real-life circumstances that apply to caring for patients, which is inherently nuanced.”

Dr. Ilyas

A version of this article appeared on Medscape.com .