User login
Panel backs limited new olaparib use in prostate cancer
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
CPAP not only solution for sleep apnea
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
Although continuous positive airway pressure (CPAP) machines are the gold standard in the management of sleep apnea, several other treatments should be considered.
“Just because you have a hammer doesn’t mean everything is a nail,” Kimberly Hardin, MD, professor of clinical internal medicine at University of California, Davis, said at the annual meeting of the American College of Physicians.
“Sleep has been underestimated in the health arena for many, many years,” said Dr. Hardin, who likened sound sleep to the “sixth vital sign.” “We know that sleep plays an integral role in our health.”
Surgical options include nasal surgery and maxillomandibular advancement surgery, also known as double-jaw surgery. Such procedures should be considered only for patients who are unwilling or unable to use CPAP or other nonsurgical treatments.
Sleep apnea occurs in 4% of adult men and 2% of adult women aged 30-60. Most commonly, obstructive sleep apnea involves the cessation or significant decrease in airflow while sleeping. The Apnea Hypopnea Index (AHI) is the number of times a patient experiences apnea or hypopnea during one night divided by the hours of sleep. Normal sleep AHI is fewer than five events per hour on average; mild sleep apnea is five to 14 events; moderate, 15-29; and severe, at least 30 events.
To identify sleep apnea, physicians have several tools at their disposal, starting with preliminary questionnaires that query patients as to whether they are having trouble falling asleep, staying asleep, or are tired during the day. Additional assessment tools include sleep lab testing and at-home testing.
At-home testing has come to include more than the common devices that are worn around the chest and nose for a night.
“It’s not very fun looking,” Dr. Hardin said of the weighty, obtrusive monitoring devices. “So lots of folks have come up with some new ways of doing things.”
These new options incorporate headbands, wrist and finger devices, arterial tonometry, and sleep rings.
Studies show that U.S. adults do not get enough sleep, and poor-quality sleep is as inadequate as insufficient sleep. Barely a third of adults get the minimum 7 hours recommended by the Centers for Disease Control and Prevention. Non-Hispanic Black adults are less likely to report sleeping 7-9 hours and are more likely to report sleeping 6 or fewer hours than are non-Hispanic White and Hispanic adults.
Dr. Hardin said doctors can advise patients to keep their bedrooms quiet, dark, and cool with no TVs or electronics, to maintain regular wake and sleep times, and to stop consuming caffeine late in the day.
Insufficient or poor sleep can have wide-ranging implications on medical conditions such as diabetes, heart disease, obesity, immunodeficiency, cognitive function, mental health, and, ultimately, mortality, according to Dr. Hardin.
“Some people say, ‘Oh, never mind, I can sleep when I’m dead,’ “ Dr. Hardin said. But such a mentality can have a bearing on life expectancy.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2023
Wireless neurostimulation safe for urge incontinence
CHICAGO – , according to new findings presented at the 2023 annual meeting of the American Urological Association.
As many as half of women in the United States aged 60 and older will experience urinary incontinence. Of those, roughly one in four experience urge urinary incontinence, marked by a sudden need to void that cannot be fully suppressed.
Researchers studied the benefits of the RENOVA iStim (BlueWind Medical) implantable tibial neuromodulation system for the treatment of overactive bladder in the OASIS trial.
Study investigator Roger R. Dmochowski, MD, MMHC, professor of urology and surgery and associate surgeon-in-chief at Vanderbilt University Medical Center, Nashville, Tenn., said the first-line treatment of urinary incontinence is lifestyle changes to retrain the bladder or physical therapy, including pelvic floor and Kegel exercises, per AUA guidelines. He said the success rate is about 30% and is not sustained. Second-line treatments include medications, which most (60%) patients stop taking by 6 months.
More than three-quarters of the 151 women who received the device responded to therapy at 1 year, and 84.6% of the patients showed improvement, according to Dr. Dmochowski.
The participants (mean age, 58.8) demonstrated a mean baseline of 4.8 urge incidents per day (standard deviation, 2.9) and 10 voids/day (SD, 3.3). No device or procedure-related serious adverse events were reported at 12 months. Half of the women no longer had symptoms on three consecutive days, Dr. Dmochowski said.
Because urge urinary incontinence is a chronic condition, “treatment with the BlueWind System will be ongoing, with frequency determined based on the patient’s response,” Dr. Dmochowski said. “The patient is then empowered to control when and where they perform therapy.”
“The device is activated by the external wearable. It’s like an on-off switch. It has a receiver within it that basically has the capacity to be turned on and off by the wearable, which is the control device. The device is in an off-position until the wearable is applied,” he said.
He said the device should be worn twice a day for about 20 minutes, with many patients using it less.
Only one implanted tibial neuromodulation device has been approved by the Food and Drug Administration – eCOIN (Valencia Technologies). The RENOVA iStim is an investigational device under review by the FDA, Dr. Dmochowski said.
In installing the device, Dr. Dmochowski said urologists use a subfascial technique to enable direct visualization of the tibial nerve and suture fixation that increases the possibility of a predictable placement. Patients use an external wearable, which activates the implant, without concern for battery longevity or replacement.
“This therapy is not associated with any adverse effects and may be beneficial for patients who do not respond to other treatments for OAB such as medications or Botox,” said Carol E. Bretschneider, MD, a urogynecologic and pelvic surgeon at Northwestern Medicine Central DuPage Hospital, outside Chicago. “Neurostimulators can be a great advanced therapy option for patients who do not respond to more conservative treatments or cannot take or tolerate a medication.”
The devices do not stimulate or strengthen muscles but act by modulating the reflexes that influence the bladder, sphincter, and pelvic floor, added Dr. Bretschneider, who was not involved in the study.
Other treatments for urge incontinence can include acupuncture, or percutaneous tibial nerve stimulation, to target the posterior tibial nerve in the ankle, which shares the same nerve root that controls the bladder, according to Aron Liaw, MD, a reconstructive urologist and assistant professor of urology at Wayne State University in Detroit. This treatment has been shown to be at least as effective as available medications, but with fewer side effects, he said.
But regular stimulation is necessary to achieve and preserve efficacy, he said.
Dr. Liaw, who was not involved in the neuromodulation study, said the benefits of a device like Renova iStim are that implantation is relatively easy and can be performed in office settings, and patients can then treat themselves at home. However, because the new study did not compare the device to other treatments or a placebo device, its relative benefits are unclear, he said,
Other treatments for urge urinary incontinence, such as bladder Botox and sacral neuromodulation, also are minimally invasive and have proven benefit, “so a device like this could well be less effective with little other advantage,” he said.
“Lifestyle changes can make a big difference, but making big lifestyle changes is not always easy,” added Dr. Liaw. “I have found neuromodulation [to be] very effective, especially in conjunction with lifestyle changes.”
BlueWind Medical funds the OASIS trial. Dr. Dmochowski reported he received no grants nor has any relevant financial relationships. Dr. Bretschneider and Dr. Liaw report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , according to new findings presented at the 2023 annual meeting of the American Urological Association.
As many as half of women in the United States aged 60 and older will experience urinary incontinence. Of those, roughly one in four experience urge urinary incontinence, marked by a sudden need to void that cannot be fully suppressed.
Researchers studied the benefits of the RENOVA iStim (BlueWind Medical) implantable tibial neuromodulation system for the treatment of overactive bladder in the OASIS trial.
Study investigator Roger R. Dmochowski, MD, MMHC, professor of urology and surgery and associate surgeon-in-chief at Vanderbilt University Medical Center, Nashville, Tenn., said the first-line treatment of urinary incontinence is lifestyle changes to retrain the bladder or physical therapy, including pelvic floor and Kegel exercises, per AUA guidelines. He said the success rate is about 30% and is not sustained. Second-line treatments include medications, which most (60%) patients stop taking by 6 months.
More than three-quarters of the 151 women who received the device responded to therapy at 1 year, and 84.6% of the patients showed improvement, according to Dr. Dmochowski.
The participants (mean age, 58.8) demonstrated a mean baseline of 4.8 urge incidents per day (standard deviation, 2.9) and 10 voids/day (SD, 3.3). No device or procedure-related serious adverse events were reported at 12 months. Half of the women no longer had symptoms on three consecutive days, Dr. Dmochowski said.
Because urge urinary incontinence is a chronic condition, “treatment with the BlueWind System will be ongoing, with frequency determined based on the patient’s response,” Dr. Dmochowski said. “The patient is then empowered to control when and where they perform therapy.”
“The device is activated by the external wearable. It’s like an on-off switch. It has a receiver within it that basically has the capacity to be turned on and off by the wearable, which is the control device. The device is in an off-position until the wearable is applied,” he said.
He said the device should be worn twice a day for about 20 minutes, with many patients using it less.
Only one implanted tibial neuromodulation device has been approved by the Food and Drug Administration – eCOIN (Valencia Technologies). The RENOVA iStim is an investigational device under review by the FDA, Dr. Dmochowski said.
In installing the device, Dr. Dmochowski said urologists use a subfascial technique to enable direct visualization of the tibial nerve and suture fixation that increases the possibility of a predictable placement. Patients use an external wearable, which activates the implant, without concern for battery longevity or replacement.
“This therapy is not associated with any adverse effects and may be beneficial for patients who do not respond to other treatments for OAB such as medications or Botox,” said Carol E. Bretschneider, MD, a urogynecologic and pelvic surgeon at Northwestern Medicine Central DuPage Hospital, outside Chicago. “Neurostimulators can be a great advanced therapy option for patients who do not respond to more conservative treatments or cannot take or tolerate a medication.”
The devices do not stimulate or strengthen muscles but act by modulating the reflexes that influence the bladder, sphincter, and pelvic floor, added Dr. Bretschneider, who was not involved in the study.
Other treatments for urge incontinence can include acupuncture, or percutaneous tibial nerve stimulation, to target the posterior tibial nerve in the ankle, which shares the same nerve root that controls the bladder, according to Aron Liaw, MD, a reconstructive urologist and assistant professor of urology at Wayne State University in Detroit. This treatment has been shown to be at least as effective as available medications, but with fewer side effects, he said.
But regular stimulation is necessary to achieve and preserve efficacy, he said.
Dr. Liaw, who was not involved in the neuromodulation study, said the benefits of a device like Renova iStim are that implantation is relatively easy and can be performed in office settings, and patients can then treat themselves at home. However, because the new study did not compare the device to other treatments or a placebo device, its relative benefits are unclear, he said,
Other treatments for urge urinary incontinence, such as bladder Botox and sacral neuromodulation, also are minimally invasive and have proven benefit, “so a device like this could well be less effective with little other advantage,” he said.
“Lifestyle changes can make a big difference, but making big lifestyle changes is not always easy,” added Dr. Liaw. “I have found neuromodulation [to be] very effective, especially in conjunction with lifestyle changes.”
BlueWind Medical funds the OASIS trial. Dr. Dmochowski reported he received no grants nor has any relevant financial relationships. Dr. Bretschneider and Dr. Liaw report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , according to new findings presented at the 2023 annual meeting of the American Urological Association.
As many as half of women in the United States aged 60 and older will experience urinary incontinence. Of those, roughly one in four experience urge urinary incontinence, marked by a sudden need to void that cannot be fully suppressed.
Researchers studied the benefits of the RENOVA iStim (BlueWind Medical) implantable tibial neuromodulation system for the treatment of overactive bladder in the OASIS trial.
Study investigator Roger R. Dmochowski, MD, MMHC, professor of urology and surgery and associate surgeon-in-chief at Vanderbilt University Medical Center, Nashville, Tenn., said the first-line treatment of urinary incontinence is lifestyle changes to retrain the bladder or physical therapy, including pelvic floor and Kegel exercises, per AUA guidelines. He said the success rate is about 30% and is not sustained. Second-line treatments include medications, which most (60%) patients stop taking by 6 months.
More than three-quarters of the 151 women who received the device responded to therapy at 1 year, and 84.6% of the patients showed improvement, according to Dr. Dmochowski.
The participants (mean age, 58.8) demonstrated a mean baseline of 4.8 urge incidents per day (standard deviation, 2.9) and 10 voids/day (SD, 3.3). No device or procedure-related serious adverse events were reported at 12 months. Half of the women no longer had symptoms on three consecutive days, Dr. Dmochowski said.
Because urge urinary incontinence is a chronic condition, “treatment with the BlueWind System will be ongoing, with frequency determined based on the patient’s response,” Dr. Dmochowski said. “The patient is then empowered to control when and where they perform therapy.”
“The device is activated by the external wearable. It’s like an on-off switch. It has a receiver within it that basically has the capacity to be turned on and off by the wearable, which is the control device. The device is in an off-position until the wearable is applied,” he said.
He said the device should be worn twice a day for about 20 minutes, with many patients using it less.
Only one implanted tibial neuromodulation device has been approved by the Food and Drug Administration – eCOIN (Valencia Technologies). The RENOVA iStim is an investigational device under review by the FDA, Dr. Dmochowski said.
In installing the device, Dr. Dmochowski said urologists use a subfascial technique to enable direct visualization of the tibial nerve and suture fixation that increases the possibility of a predictable placement. Patients use an external wearable, which activates the implant, without concern for battery longevity or replacement.
“This therapy is not associated with any adverse effects and may be beneficial for patients who do not respond to other treatments for OAB such as medications or Botox,” said Carol E. Bretschneider, MD, a urogynecologic and pelvic surgeon at Northwestern Medicine Central DuPage Hospital, outside Chicago. “Neurostimulators can be a great advanced therapy option for patients who do not respond to more conservative treatments or cannot take or tolerate a medication.”
The devices do not stimulate or strengthen muscles but act by modulating the reflexes that influence the bladder, sphincter, and pelvic floor, added Dr. Bretschneider, who was not involved in the study.
Other treatments for urge incontinence can include acupuncture, or percutaneous tibial nerve stimulation, to target the posterior tibial nerve in the ankle, which shares the same nerve root that controls the bladder, according to Aron Liaw, MD, a reconstructive urologist and assistant professor of urology at Wayne State University in Detroit. This treatment has been shown to be at least as effective as available medications, but with fewer side effects, he said.
But regular stimulation is necessary to achieve and preserve efficacy, he said.
Dr. Liaw, who was not involved in the neuromodulation study, said the benefits of a device like Renova iStim are that implantation is relatively easy and can be performed in office settings, and patients can then treat themselves at home. However, because the new study did not compare the device to other treatments or a placebo device, its relative benefits are unclear, he said,
Other treatments for urge urinary incontinence, such as bladder Botox and sacral neuromodulation, also are minimally invasive and have proven benefit, “so a device like this could well be less effective with little other advantage,” he said.
“Lifestyle changes can make a big difference, but making big lifestyle changes is not always easy,” added Dr. Liaw. “I have found neuromodulation [to be] very effective, especially in conjunction with lifestyle changes.”
BlueWind Medical funds the OASIS trial. Dr. Dmochowski reported he received no grants nor has any relevant financial relationships. Dr. Bretschneider and Dr. Liaw report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AUA 2023
Gender-diverse teens face barriers to physical activity
WASHINGTON – in a poster presented at the Pediatric Academic Societies annual meeting. Other barriers included body dissatisfaction and discomfort or pain from binding or tucking, based on data from 160 individuals.
Previous studies suggest that gender-diverse teens have lower levels of physical activity than cisgender teens, but data on the specific barriers to physical activity reported by gender-diverse adolescents are lacking, according to Karishma Desai, BA, a medical student at Northwestern University, Chicago, and colleagues.
The researchers reviewed data from adolescents aged 13-18 years who identified as transgender or nonbinary and lived in the United States. Participants were recruited through flyers, wallet cards, email, and social media. They completed an online survey that included questions on preferred types of physical activity and potential barriers to physical activity. Major barriers were defined as items that “almost always” or “always” got in the way of physical activity.
Overall, 51% of the participants identified as female/transfeminine, 31% as male/transmasculine, 9% as genderqueer or agender, 8% as nonbinary, and 1% as unsure. A total of 86 participants were assigned male at birth, 73 were assigned female, and 1 was assigned intersex or other. Nearly all of the participants (96%) had begun social transition; approximately half (48%) reported using a chest binder, and 75% had been or were currently taking gender-affirming hormones.
Potential negative judgment from others was the top barrier to physical activity (cited by 39% of participants), followed by body dissatisfaction from gender dysphoria (38%) and discomfort with the available options for locker rooms or changing rooms (38%). Approximately one-third (36%) of respondents reported physical discomfort or pain from binding or tucking as a barrier to physical activity, and 34% cited discomfort with requirements for a physical activity uniform or athletic clothing at school. Other gender-diverse specific barriers to physical activity included bullying related to being transgender (31%) and the inability to participate in a group of choice because of gender identity (24%).
In addition, participants cited general barriers to physical activity including bullying related to weight (33%), dissatisfaction with weight or size (31%), and bullying in general or for reasons other than gender status (29%).
However, more than 50% of respondents said they were comfortable or very comfortable (4 or 5 on a 5-point Likert Scale) with physical activity in the settings of coed or all-gender teams (61%) or engaging in individual activities (71%). By contrast, 36% were comfortable or very comfortable with a team, group, or class that aligned with sex assignment at birth.
The majority of participants (81%) were comfortable or very comfortable with their homes or a private location as a setting for physical activity, 54% with a public space such as a park, and 43% with a school setting.
Increasing gender congruence was the biggest facilitator of physical activity, reported by 53% of participants, the researchers noted. Other facilitators of physical activity included increasing body satisfaction (43%), staying healthy to avoid long-term health problems in the future (43%), and staying healthy to prepare for gender-related surgery in the future (18%).
The study findings were limited by the use of self-reports and the use of a convenience sample, as well as the lack of data on race, the researchers noted. However, the results suggest that access to all-gender teams, standardizing physical activity clothing, and increasing inclusive facilities may promote greater physical activity participation by gender-diverse adolescents, and offering private or individual options may increase comfort with physical activity, they concluded.
Study provides teens’ perspectives
The current study is especially timely given the recent passage by the U.S. House of Representatives of the anti-trans sports bill preventing transgender women and girls from playing on sports teams “consistent with their gender identity,” said Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, in an interview. Ms. Thew was not involved in the current study.
“The House bill seeks to amend federal law to require that sex shall be recognized based solely on a person’s reproductive biology and genetics at birth, for the purpose of determining compliance with Title IX in athletics,” Ms. Thew said.
“Despite political responses to sports participation for transgender adolescents, we have not heard the perspective of the teens themselves,” she emphasized. “It is imperative for parents, coaches, and clinicians to hear the adolescents’ concerns so they can advocate for the students and provide the needed support.” In addition, Ms. Thew noted, “these concerns may also provide overdue changes to the required uniforms described for specific sports.”
Ms. Thew said she was surprised by the finding of transgender teens’ comfort with coed teams and individual activities, both of which may be opportunities to promote physical activity for transgender adolescents.
However, she added that she was not surprised by some of the results. “Many transgender adolescents experience the discomfort and further body dysmorphia of being put into gender-conforming attire such as swimwear, spandex shorts for female volleyball players, or field hockey skirts, for example.”
Although many schools are establishing safe, comfortable places for all adolescents to change clothing prior to physical education and sports participation, “resources are limited, and students and parents need to advocate within the school system,” Ms. Thew noted.
“We as a society, including athletic clothing makers, need to hear the testimony of transgender adolescents on the discomfort from body modifications to better support and innovate attire to meet their needs,” she added.
“The take-home message for clinicians is twofold,” said Ms. Thew. “Clinicians need to advocate for transgender patients to have the same opportunities as all teens when it comes to sports participation and physical activity. Also, clinicians need to ask all adolescents about their comfort in participating in physical activity both on club/school teams and independently,” she said. “If barriers are identified, clinicians need to work to support the adolescent with alternative activities/attire that will promote healthy physical activities for overall health.”
The current study also suggests that transgender adolescents who may have interest in, but discomfort with, physical activity should be redirected to coed or individual sports available in their communities, Ms. Thew added.
More research is needed on innovative sports attire that would improve comfort for transgender adolescents and thereby encourage physical activity, Ms. Thew told this news organization. More data also are needed on which sports transgender adolescents participate in and why, and how these activities might be promoted, she said.
Finally, more research will be needed to examine the impact of the recent House bills on physical activity for transgender youth, Ms. Thew said.
The study was supported by the Potocsnak Family Division of Adolescent and Young Adult Medicine at Ann and Robert H. Lurie’s Children’s Hospital of Chicago. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose, but she serves on the Editorial Advisory Board of Pediatric News.
WASHINGTON – in a poster presented at the Pediatric Academic Societies annual meeting. Other barriers included body dissatisfaction and discomfort or pain from binding or tucking, based on data from 160 individuals.
Previous studies suggest that gender-diverse teens have lower levels of physical activity than cisgender teens, but data on the specific barriers to physical activity reported by gender-diverse adolescents are lacking, according to Karishma Desai, BA, a medical student at Northwestern University, Chicago, and colleagues.
The researchers reviewed data from adolescents aged 13-18 years who identified as transgender or nonbinary and lived in the United States. Participants were recruited through flyers, wallet cards, email, and social media. They completed an online survey that included questions on preferred types of physical activity and potential barriers to physical activity. Major barriers were defined as items that “almost always” or “always” got in the way of physical activity.
Overall, 51% of the participants identified as female/transfeminine, 31% as male/transmasculine, 9% as genderqueer or agender, 8% as nonbinary, and 1% as unsure. A total of 86 participants were assigned male at birth, 73 were assigned female, and 1 was assigned intersex or other. Nearly all of the participants (96%) had begun social transition; approximately half (48%) reported using a chest binder, and 75% had been or were currently taking gender-affirming hormones.
Potential negative judgment from others was the top barrier to physical activity (cited by 39% of participants), followed by body dissatisfaction from gender dysphoria (38%) and discomfort with the available options for locker rooms or changing rooms (38%). Approximately one-third (36%) of respondents reported physical discomfort or pain from binding or tucking as a barrier to physical activity, and 34% cited discomfort with requirements for a physical activity uniform or athletic clothing at school. Other gender-diverse specific barriers to physical activity included bullying related to being transgender (31%) and the inability to participate in a group of choice because of gender identity (24%).
In addition, participants cited general barriers to physical activity including bullying related to weight (33%), dissatisfaction with weight or size (31%), and bullying in general or for reasons other than gender status (29%).
However, more than 50% of respondents said they were comfortable or very comfortable (4 or 5 on a 5-point Likert Scale) with physical activity in the settings of coed or all-gender teams (61%) or engaging in individual activities (71%). By contrast, 36% were comfortable or very comfortable with a team, group, or class that aligned with sex assignment at birth.
The majority of participants (81%) were comfortable or very comfortable with their homes or a private location as a setting for physical activity, 54% with a public space such as a park, and 43% with a school setting.
Increasing gender congruence was the biggest facilitator of physical activity, reported by 53% of participants, the researchers noted. Other facilitators of physical activity included increasing body satisfaction (43%), staying healthy to avoid long-term health problems in the future (43%), and staying healthy to prepare for gender-related surgery in the future (18%).
The study findings were limited by the use of self-reports and the use of a convenience sample, as well as the lack of data on race, the researchers noted. However, the results suggest that access to all-gender teams, standardizing physical activity clothing, and increasing inclusive facilities may promote greater physical activity participation by gender-diverse adolescents, and offering private or individual options may increase comfort with physical activity, they concluded.
Study provides teens’ perspectives
The current study is especially timely given the recent passage by the U.S. House of Representatives of the anti-trans sports bill preventing transgender women and girls from playing on sports teams “consistent with their gender identity,” said Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, in an interview. Ms. Thew was not involved in the current study.
“The House bill seeks to amend federal law to require that sex shall be recognized based solely on a person’s reproductive biology and genetics at birth, for the purpose of determining compliance with Title IX in athletics,” Ms. Thew said.
“Despite political responses to sports participation for transgender adolescents, we have not heard the perspective of the teens themselves,” she emphasized. “It is imperative for parents, coaches, and clinicians to hear the adolescents’ concerns so they can advocate for the students and provide the needed support.” In addition, Ms. Thew noted, “these concerns may also provide overdue changes to the required uniforms described for specific sports.”
Ms. Thew said she was surprised by the finding of transgender teens’ comfort with coed teams and individual activities, both of which may be opportunities to promote physical activity for transgender adolescents.
However, she added that she was not surprised by some of the results. “Many transgender adolescents experience the discomfort and further body dysmorphia of being put into gender-conforming attire such as swimwear, spandex shorts for female volleyball players, or field hockey skirts, for example.”
Although many schools are establishing safe, comfortable places for all adolescents to change clothing prior to physical education and sports participation, “resources are limited, and students and parents need to advocate within the school system,” Ms. Thew noted.
“We as a society, including athletic clothing makers, need to hear the testimony of transgender adolescents on the discomfort from body modifications to better support and innovate attire to meet their needs,” she added.
“The take-home message for clinicians is twofold,” said Ms. Thew. “Clinicians need to advocate for transgender patients to have the same opportunities as all teens when it comes to sports participation and physical activity. Also, clinicians need to ask all adolescents about their comfort in participating in physical activity both on club/school teams and independently,” she said. “If barriers are identified, clinicians need to work to support the adolescent with alternative activities/attire that will promote healthy physical activities for overall health.”
The current study also suggests that transgender adolescents who may have interest in, but discomfort with, physical activity should be redirected to coed or individual sports available in their communities, Ms. Thew added.
More research is needed on innovative sports attire that would improve comfort for transgender adolescents and thereby encourage physical activity, Ms. Thew told this news organization. More data also are needed on which sports transgender adolescents participate in and why, and how these activities might be promoted, she said.
Finally, more research will be needed to examine the impact of the recent House bills on physical activity for transgender youth, Ms. Thew said.
The study was supported by the Potocsnak Family Division of Adolescent and Young Adult Medicine at Ann and Robert H. Lurie’s Children’s Hospital of Chicago. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose, but she serves on the Editorial Advisory Board of Pediatric News.
WASHINGTON – in a poster presented at the Pediatric Academic Societies annual meeting. Other barriers included body dissatisfaction and discomfort or pain from binding or tucking, based on data from 160 individuals.
Previous studies suggest that gender-diverse teens have lower levels of physical activity than cisgender teens, but data on the specific barriers to physical activity reported by gender-diverse adolescents are lacking, according to Karishma Desai, BA, a medical student at Northwestern University, Chicago, and colleagues.
The researchers reviewed data from adolescents aged 13-18 years who identified as transgender or nonbinary and lived in the United States. Participants were recruited through flyers, wallet cards, email, and social media. They completed an online survey that included questions on preferred types of physical activity and potential barriers to physical activity. Major barriers were defined as items that “almost always” or “always” got in the way of physical activity.
Overall, 51% of the participants identified as female/transfeminine, 31% as male/transmasculine, 9% as genderqueer or agender, 8% as nonbinary, and 1% as unsure. A total of 86 participants were assigned male at birth, 73 were assigned female, and 1 was assigned intersex or other. Nearly all of the participants (96%) had begun social transition; approximately half (48%) reported using a chest binder, and 75% had been or were currently taking gender-affirming hormones.
Potential negative judgment from others was the top barrier to physical activity (cited by 39% of participants), followed by body dissatisfaction from gender dysphoria (38%) and discomfort with the available options for locker rooms or changing rooms (38%). Approximately one-third (36%) of respondents reported physical discomfort or pain from binding or tucking as a barrier to physical activity, and 34% cited discomfort with requirements for a physical activity uniform or athletic clothing at school. Other gender-diverse specific barriers to physical activity included bullying related to being transgender (31%) and the inability to participate in a group of choice because of gender identity (24%).
In addition, participants cited general barriers to physical activity including bullying related to weight (33%), dissatisfaction with weight or size (31%), and bullying in general or for reasons other than gender status (29%).
However, more than 50% of respondents said they were comfortable or very comfortable (4 or 5 on a 5-point Likert Scale) with physical activity in the settings of coed or all-gender teams (61%) or engaging in individual activities (71%). By contrast, 36% were comfortable or very comfortable with a team, group, or class that aligned with sex assignment at birth.
The majority of participants (81%) were comfortable or very comfortable with their homes or a private location as a setting for physical activity, 54% with a public space such as a park, and 43% with a school setting.
Increasing gender congruence was the biggest facilitator of physical activity, reported by 53% of participants, the researchers noted. Other facilitators of physical activity included increasing body satisfaction (43%), staying healthy to avoid long-term health problems in the future (43%), and staying healthy to prepare for gender-related surgery in the future (18%).
The study findings were limited by the use of self-reports and the use of a convenience sample, as well as the lack of data on race, the researchers noted. However, the results suggest that access to all-gender teams, standardizing physical activity clothing, and increasing inclusive facilities may promote greater physical activity participation by gender-diverse adolescents, and offering private or individual options may increase comfort with physical activity, they concluded.
Study provides teens’ perspectives
The current study is especially timely given the recent passage by the U.S. House of Representatives of the anti-trans sports bill preventing transgender women and girls from playing on sports teams “consistent with their gender identity,” said Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, in an interview. Ms. Thew was not involved in the current study.
“The House bill seeks to amend federal law to require that sex shall be recognized based solely on a person’s reproductive biology and genetics at birth, for the purpose of determining compliance with Title IX in athletics,” Ms. Thew said.
“Despite political responses to sports participation for transgender adolescents, we have not heard the perspective of the teens themselves,” she emphasized. “It is imperative for parents, coaches, and clinicians to hear the adolescents’ concerns so they can advocate for the students and provide the needed support.” In addition, Ms. Thew noted, “these concerns may also provide overdue changes to the required uniforms described for specific sports.”
Ms. Thew said she was surprised by the finding of transgender teens’ comfort with coed teams and individual activities, both of which may be opportunities to promote physical activity for transgender adolescents.
However, she added that she was not surprised by some of the results. “Many transgender adolescents experience the discomfort and further body dysmorphia of being put into gender-conforming attire such as swimwear, spandex shorts for female volleyball players, or field hockey skirts, for example.”
Although many schools are establishing safe, comfortable places for all adolescents to change clothing prior to physical education and sports participation, “resources are limited, and students and parents need to advocate within the school system,” Ms. Thew noted.
“We as a society, including athletic clothing makers, need to hear the testimony of transgender adolescents on the discomfort from body modifications to better support and innovate attire to meet their needs,” she added.
“The take-home message for clinicians is twofold,” said Ms. Thew. “Clinicians need to advocate for transgender patients to have the same opportunities as all teens when it comes to sports participation and physical activity. Also, clinicians need to ask all adolescents about their comfort in participating in physical activity both on club/school teams and independently,” she said. “If barriers are identified, clinicians need to work to support the adolescent with alternative activities/attire that will promote healthy physical activities for overall health.”
The current study also suggests that transgender adolescents who may have interest in, but discomfort with, physical activity should be redirected to coed or individual sports available in their communities, Ms. Thew added.
More research is needed on innovative sports attire that would improve comfort for transgender adolescents and thereby encourage physical activity, Ms. Thew told this news organization. More data also are needed on which sports transgender adolescents participate in and why, and how these activities might be promoted, she said.
Finally, more research will be needed to examine the impact of the recent House bills on physical activity for transgender youth, Ms. Thew said.
The study was supported by the Potocsnak Family Division of Adolescent and Young Adult Medicine at Ann and Robert H. Lurie’s Children’s Hospital of Chicago. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose, but she serves on the Editorial Advisory Board of Pediatric News.
AT PAS 2023
FDA expands atogepant approval to include chronic migraine
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
Malaria: Not just someone else’s problem
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
What is the most dangerous animal on Earth? Which one has killed more humans since we first began walking upright?
The mind leaps to the vicious and dangerous – great white sharks. lions. tigers. crocodiles. The fearsome predators of the planet But realistically, more people are killed and injured by large herbivores each year than predators. Just watch news updates from Yellowstone during their busy season.
Anyway, the correct answer is ... none of the above.
It’s the mosquito, and the many microbes it’s a vector for. Malaria, in particular. Even the once-devastating bubonic plague is no longer a major concern.
What do Presidents Washington, Kennedy, Eisenhower, Lincoln, Monroe, Grant, Garfield, Jackson, Teddy Roosevelt, and other historical VIPs like Oliver Cromwell, King Tut, and numerous kings, queens, and popes all have in common? They all had malaria. Cromwell, Tut, and many royal and religious figures died of it.
You can make a solid argument that malaria is the disease that’s affected the course of history more than any other (you could make a good case for the plague, too, but it’s less relevant today). The control of malaria is what allowed the Panama canal to happen.
I’m bringing this up because, mostly overlooked in the news recently as we argued about light beer endorsements, TV pundits, and the NFL draft, is the approval and gradual increase in use of a malaria vaccine.
This is a pretty big deal given the scope of the problem and the fact that the most effective prevention up until recently was a mosquito net.
We tend to see malaria as someone else’s problem, something that affects the tropics, but forget that as recently as the 1940s it was still common in the U.S. During the Civil War as many as 1 million soldiers were infected with it. Given the right conditions it could easily return here.
Which is why we should be more aware of these things. As COVID showed, infectious diseases are never some other country’s, or continent’s, problem. They affect all of us either directly or indirectly. In the interconnected economies of the world illnesses in one area can spread to others. Even if they don’t they can still have significant effects on supply chains, since so much of what we depend on comes from somewhere else.
COVID, by comparison, is small beer. Just think about smallpox, or the plague, or polio, as to what an unchecked disease can do to a society until medicine catches up with it.
There will always be new diseases. Microbes and humans have been in a state of hostilities for a few million years now, and likely always will be. But every victory along the way is a victory for everyone, regardless of who they are or where they live.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Getting a white-bagging exemption: A win for the patient, employer, and rheumatologist
Whether it’s filling out a prior authorization form or testifying before Congress, it is an action we perform that ultimately helps our patients achieve that care. We are familiar with many of the obstacles that block the path to the best care and interfere with our patient-doctor relationships. Much work has been done to pass legislation in the states to mitigate some of those obstacles, such as unreasonable step therapy regimens, nonmedical switching, and copay accumulators.
Unfortunately, that state legislation does not cover patients who work for companies that are self-insured. Self-insured employers, which account for about 60% of America’s workers, directly pay for the health benefits offered to employees instead of buying “fully funded” insurance plans. Most of those self-funded plans fall under “ERISA” protections and are regulated by the federal Department of Labor. ERISA stands for Employee Retirement Income Security Act. The law, which was enacted in 1974, also covers employee health plans. These plans must act as a fiduciary, meaning they must look after the well-being of the employees, including their finances and those of the plan itself.
The Coalition of State Rheumatology Organizations (CSRO) has learned of a number of issues involving patients who work for self-funded companies, regulated by ERISA. One such issue is that of mandated “white bagging.” White bagging has been discussed in “Rheum for Action” in the past. There is a long list of white-bagging problems, including dosing issues, lack of “chain of custody” with the medications, delays in treatment, mandatory up-front payments by the patient, and wastage of unused medication. However, there is another issue that is of concern not only to the employees (our patients) but to the employer as well.
Employers’ fiduciary responsibility
As mentioned earlier, the employers who self insure are responsible for the financial well-being of their employee and the plan itself. Therefore, if certain practices are mandated within the health plan that harm our patients or the plan financially, the company could be in violation of their fiduciary duty. Rheumatologists have said that buying and billing the drug to the medical side of the health plan in many cases costs much less than white bagging. Conceivably, that could result in breach of an employer’s fiduciary duty to their employee.
Evidence for violating fiduciary duty
CSRO recently received redacted receipts comparing costs between the two models of drug acquisition for a patient in an ERISA plan. White bagging for the patient occurred in 2021, and in 2022 an exemption was granted for the rheumatologist to buy and bill the administered medication. Unfortunately, the exemption to buy and bill in 2023 was denied and continues to be denied (as of this writing). A comparison of the receipts revealed the company was charged over $40,000 for the white-bagged medication in 2021, and the patient’s cost share for that year was $525. Under the traditional buy-and-bill acquisition model in 2022, the company was charged around $12,000 for the medication and the patient’s cost share was $30. There is a clear difference in cost to the employee and plan between the two acquisition models.
Is this major company unknowingly violating its fiduciary duty by mandating white bagging as per their contract with one of the three big pharmacy benefit managers (PBMs)? If so, how does something like this happen with a large national company that has ERISA attorneys looking over the contracts with the PBMs?
Why is white bagging mandated?
Often, white bagging is mandated because the cost of infusions in a hospital outpatient facility can be very high. Nationally, it has been shown that hospitals charge four to five times the cost they paid for the drug, and the 100 most expensive hospitals charge 10-18 times the cost of their drugs. With these up-charges, white bagging could easily be a lower cost for employee and company. But across-the-board mandating of white bagging ignores that physician office–based infusions may offer a much lower cost to employees and the employer.
Another reason large and small self-funded companies may unknowingly sign contracts that are often more profitable to the PBM than to the employer is that the employer pharmacy benefit consultants are paid handsomely by the big PBMs and have been known to “rig” the contract in favor of the PBM, according to Paul Holmes, an ERISA attorney with a focus in pharmacy health plan contracts. Clearly, the PBM profits more with white-bagged medicines billed through the pharmacy (PBM) side of insurance as opposed to buy-and-bill medications that are billed on the medical side of insurance. So mandated white bagging is often included in these contracts, ignoring the lower cost in an infusion suite at a physician’s office.
Suggestions for employers
Employers and employees should be able to obtain the costs of mandated, white-bagged drugs from their PBMs because the Consolidated Appropriations Act of 2021 (CAA) mandates that group health plans ensure access to cost data. The employer should also have access to their consultant’s compensation from the PBM as Section 202 in the CAA states that employer benefit consultants must “disclose actual and anticipated cash and non-cash compensation they expect to earn in connection with the sale, renewal, and extension of group health insurance.”
It would be wise for all self-insured companies to use this section to see how much their consultants are being influenced by the company that they are recommending. Additionally, the companies should consider hiring ERISA attorneys that understand not only the legalese of the contract with a PBM but also the pharmacy lingo, such as the difference between maximum allowable cost, average wholesale price, average sales price, and average manufacturer’s price.
Suggestion for the rheumatologist
This leads to a suggestion to rheumatologists trying to get an exemption from mandated white bagging. If a patient has already had white-bagged medication, have them obtain a receipt from the PBM for their charges to the plan for the medication. If the patient has not gone through the white bagging yet, the PBM should be able to tell the plan the cost of the white-bagged medication and the cost to the patient. Compare those costs with what would be charged through buy and bill, and if it is less, present that evidence to the employer and remind them of their fiduciary responsibility to their employees.
Granted, this process may take more effort than filling out a prior authorization, but getting the white-bag exemption will help the patient, the employer, and the rheumatologist in the long run. A win-win-win!
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 rhnews@mdedge.com.
Whether it’s filling out a prior authorization form or testifying before Congress, it is an action we perform that ultimately helps our patients achieve that care. We are familiar with many of the obstacles that block the path to the best care and interfere with our patient-doctor relationships. Much work has been done to pass legislation in the states to mitigate some of those obstacles, such as unreasonable step therapy regimens, nonmedical switching, and copay accumulators.
Unfortunately, that state legislation does not cover patients who work for companies that are self-insured. Self-insured employers, which account for about 60% of America’s workers, directly pay for the health benefits offered to employees instead of buying “fully funded” insurance plans. Most of those self-funded plans fall under “ERISA” protections and are regulated by the federal Department of Labor. ERISA stands for Employee Retirement Income Security Act. The law, which was enacted in 1974, also covers employee health plans. These plans must act as a fiduciary, meaning they must look after the well-being of the employees, including their finances and those of the plan itself.
The Coalition of State Rheumatology Organizations (CSRO) has learned of a number of issues involving patients who work for self-funded companies, regulated by ERISA. One such issue is that of mandated “white bagging.” White bagging has been discussed in “Rheum for Action” in the past. There is a long list of white-bagging problems, including dosing issues, lack of “chain of custody” with the medications, delays in treatment, mandatory up-front payments by the patient, and wastage of unused medication. However, there is another issue that is of concern not only to the employees (our patients) but to the employer as well.
Employers’ fiduciary responsibility
As mentioned earlier, the employers who self insure are responsible for the financial well-being of their employee and the plan itself. Therefore, if certain practices are mandated within the health plan that harm our patients or the plan financially, the company could be in violation of their fiduciary duty. Rheumatologists have said that buying and billing the drug to the medical side of the health plan in many cases costs much less than white bagging. Conceivably, that could result in breach of an employer’s fiduciary duty to their employee.
Evidence for violating fiduciary duty
CSRO recently received redacted receipts comparing costs between the two models of drug acquisition for a patient in an ERISA plan. White bagging for the patient occurred in 2021, and in 2022 an exemption was granted for the rheumatologist to buy and bill the administered medication. Unfortunately, the exemption to buy and bill in 2023 was denied and continues to be denied (as of this writing). A comparison of the receipts revealed the company was charged over $40,000 for the white-bagged medication in 2021, and the patient’s cost share for that year was $525. Under the traditional buy-and-bill acquisition model in 2022, the company was charged around $12,000 for the medication and the patient’s cost share was $30. There is a clear difference in cost to the employee and plan between the two acquisition models.
Is this major company unknowingly violating its fiduciary duty by mandating white bagging as per their contract with one of the three big pharmacy benefit managers (PBMs)? If so, how does something like this happen with a large national company that has ERISA attorneys looking over the contracts with the PBMs?
Why is white bagging mandated?
Often, white bagging is mandated because the cost of infusions in a hospital outpatient facility can be very high. Nationally, it has been shown that hospitals charge four to five times the cost they paid for the drug, and the 100 most expensive hospitals charge 10-18 times the cost of their drugs. With these up-charges, white bagging could easily be a lower cost for employee and company. But across-the-board mandating of white bagging ignores that physician office–based infusions may offer a much lower cost to employees and the employer.
Another reason large and small self-funded companies may unknowingly sign contracts that are often more profitable to the PBM than to the employer is that the employer pharmacy benefit consultants are paid handsomely by the big PBMs and have been known to “rig” the contract in favor of the PBM, according to Paul Holmes, an ERISA attorney with a focus in pharmacy health plan contracts. Clearly, the PBM profits more with white-bagged medicines billed through the pharmacy (PBM) side of insurance as opposed to buy-and-bill medications that are billed on the medical side of insurance. So mandated white bagging is often included in these contracts, ignoring the lower cost in an infusion suite at a physician’s office.
Suggestions for employers
Employers and employees should be able to obtain the costs of mandated, white-bagged drugs from their PBMs because the Consolidated Appropriations Act of 2021 (CAA) mandates that group health plans ensure access to cost data. The employer should also have access to their consultant’s compensation from the PBM as Section 202 in the CAA states that employer benefit consultants must “disclose actual and anticipated cash and non-cash compensation they expect to earn in connection with the sale, renewal, and extension of group health insurance.”
It would be wise for all self-insured companies to use this section to see how much their consultants are being influenced by the company that they are recommending. Additionally, the companies should consider hiring ERISA attorneys that understand not only the legalese of the contract with a PBM but also the pharmacy lingo, such as the difference between maximum allowable cost, average wholesale price, average sales price, and average manufacturer’s price.
Suggestion for the rheumatologist
This leads to a suggestion to rheumatologists trying to get an exemption from mandated white bagging. If a patient has already had white-bagged medication, have them obtain a receipt from the PBM for their charges to the plan for the medication. If the patient has not gone through the white bagging yet, the PBM should be able to tell the plan the cost of the white-bagged medication and the cost to the patient. Compare those costs with what would be charged through buy and bill, and if it is less, present that evidence to the employer and remind them of their fiduciary responsibility to their employees.
Granted, this process may take more effort than filling out a prior authorization, but getting the white-bag exemption will help the patient, the employer, and the rheumatologist in the long run. A win-win-win!
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 rhnews@mdedge.com.
Whether it’s filling out a prior authorization form or testifying before Congress, it is an action we perform that ultimately helps our patients achieve that care. We are familiar with many of the obstacles that block the path to the best care and interfere with our patient-doctor relationships. Much work has been done to pass legislation in the states to mitigate some of those obstacles, such as unreasonable step therapy regimens, nonmedical switching, and copay accumulators.
Unfortunately, that state legislation does not cover patients who work for companies that are self-insured. Self-insured employers, which account for about 60% of America’s workers, directly pay for the health benefits offered to employees instead of buying “fully funded” insurance plans. Most of those self-funded plans fall under “ERISA” protections and are regulated by the federal Department of Labor. ERISA stands for Employee Retirement Income Security Act. The law, which was enacted in 1974, also covers employee health plans. These plans must act as a fiduciary, meaning they must look after the well-being of the employees, including their finances and those of the plan itself.
The Coalition of State Rheumatology Organizations (CSRO) has learned of a number of issues involving patients who work for self-funded companies, regulated by ERISA. One such issue is that of mandated “white bagging.” White bagging has been discussed in “Rheum for Action” in the past. There is a long list of white-bagging problems, including dosing issues, lack of “chain of custody” with the medications, delays in treatment, mandatory up-front payments by the patient, and wastage of unused medication. However, there is another issue that is of concern not only to the employees (our patients) but to the employer as well.
Employers’ fiduciary responsibility
As mentioned earlier, the employers who self insure are responsible for the financial well-being of their employee and the plan itself. Therefore, if certain practices are mandated within the health plan that harm our patients or the plan financially, the company could be in violation of their fiduciary duty. Rheumatologists have said that buying and billing the drug to the medical side of the health plan in many cases costs much less than white bagging. Conceivably, that could result in breach of an employer’s fiduciary duty to their employee.
Evidence for violating fiduciary duty
CSRO recently received redacted receipts comparing costs between the two models of drug acquisition for a patient in an ERISA plan. White bagging for the patient occurred in 2021, and in 2022 an exemption was granted for the rheumatologist to buy and bill the administered medication. Unfortunately, the exemption to buy and bill in 2023 was denied and continues to be denied (as of this writing). A comparison of the receipts revealed the company was charged over $40,000 for the white-bagged medication in 2021, and the patient’s cost share for that year was $525. Under the traditional buy-and-bill acquisition model in 2022, the company was charged around $12,000 for the medication and the patient’s cost share was $30. There is a clear difference in cost to the employee and plan between the two acquisition models.
Is this major company unknowingly violating its fiduciary duty by mandating white bagging as per their contract with one of the three big pharmacy benefit managers (PBMs)? If so, how does something like this happen with a large national company that has ERISA attorneys looking over the contracts with the PBMs?
Why is white bagging mandated?
Often, white bagging is mandated because the cost of infusions in a hospital outpatient facility can be very high. Nationally, it has been shown that hospitals charge four to five times the cost they paid for the drug, and the 100 most expensive hospitals charge 10-18 times the cost of their drugs. With these up-charges, white bagging could easily be a lower cost for employee and company. But across-the-board mandating of white bagging ignores that physician office–based infusions may offer a much lower cost to employees and the employer.
Another reason large and small self-funded companies may unknowingly sign contracts that are often more profitable to the PBM than to the employer is that the employer pharmacy benefit consultants are paid handsomely by the big PBMs and have been known to “rig” the contract in favor of the PBM, according to Paul Holmes, an ERISA attorney with a focus in pharmacy health plan contracts. Clearly, the PBM profits more with white-bagged medicines billed through the pharmacy (PBM) side of insurance as opposed to buy-and-bill medications that are billed on the medical side of insurance. So mandated white bagging is often included in these contracts, ignoring the lower cost in an infusion suite at a physician’s office.
Suggestions for employers
Employers and employees should be able to obtain the costs of mandated, white-bagged drugs from their PBMs because the Consolidated Appropriations Act of 2021 (CAA) mandates that group health plans ensure access to cost data. The employer should also have access to their consultant’s compensation from the PBM as Section 202 in the CAA states that employer benefit consultants must “disclose actual and anticipated cash and non-cash compensation they expect to earn in connection with the sale, renewal, and extension of group health insurance.”
It would be wise for all self-insured companies to use this section to see how much their consultants are being influenced by the company that they are recommending. Additionally, the companies should consider hiring ERISA attorneys that understand not only the legalese of the contract with a PBM but also the pharmacy lingo, such as the difference between maximum allowable cost, average wholesale price, average sales price, and average manufacturer’s price.
Suggestion for the rheumatologist
This leads to a suggestion to rheumatologists trying to get an exemption from mandated white bagging. If a patient has already had white-bagged medication, have them obtain a receipt from the PBM for their charges to the plan for the medication. If the patient has not gone through the white bagging yet, the PBM should be able to tell the plan the cost of the white-bagged medication and the cost to the patient. Compare those costs with what would be charged through buy and bill, and if it is less, present that evidence to the employer and remind them of their fiduciary responsibility to their employees.
Granted, this process may take more effort than filling out a prior authorization, but getting the white-bag exemption will help the patient, the employer, and the rheumatologist in the long run. A win-win-win!
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 rhnews@mdedge.com.
Subcutaneous Nodule on the Postauricular Neck
The Diagnosis: Pleomorphic Lipoma
Pleomorphic lipoma is a rare, benign, adipocytic neoplasm that presents in the subcutaneous tissues of the upper shoulder, back, or neck. It predominantly affects men aged 50 to 70 years. Most lesions are situated in the subcutaneous tissues; few cases of intramuscular and retroperitoneal tumors have been reported.1 Clinically, pleomorphic lipomas present as painless, well-circumscribed lesions of the subcutaneous tissue that often resemble a lipoma or occasionally may be mistaken for liposarcoma. Histopathologic examination of ordinary lipomas reveals uniform mature adipocytes. However, pleomorphic lipomas consist of a mixture of multinucleated floretlike giant cells, variable-sized adipocytes, and fibrous tissue (ropy collagen bundles) with some myxoid and spindled areas.1,2 The most characteristic histologic feature of pleomorphic lipoma is multinucleated floretlike giant cells. The nuclei of these giant cells appear hyperchromatic, enlarged, and disposed to the periphery of the cell in a circular pattern. Additionally, tumors frequently contain excess mature dense collagen bundles that are strongly refractile in polarized light. Numerous mast cells are present. Atypical lipoblasts and capillary networks commonly are not visible in pleomorphic lipoma.3 The spindle cells express CD34 on immunohistochemistry. Loss of Rb-1 expression is typical.4
Dermatofibrosarcoma protuberans is a slow-growing soft tissue sarcoma that commonly begins as a pink or violet plaque on the trunk or upper limbs. Involvement of the head or neck accounts for only 10% to 15% of cases.5 This tumor has low metastatic potential but is highly infiltrative of surrounding tissues. It is associated with a translocation between chromosomes 22 and 17, leading to the fusion of the platelet-derived growth factor subunit β, PDGFB, and collagen type 1α1, COL1A1, genes.5 Clinically, patients often report that the lesion was present for several years prior to presentation with general stability in size and shape. Eventually, untreated lesions progress to become nodules or tumors and may even bleed or ulcerate. Histology reveals a storiform spindle cell proliferation throughout the dermis with infiltration into subcutaneous fat, commonly appearing in a honeycomblike pattern (Figure 1). Numerous histologic variants exist, including myxoid, sclerosing, pigmented (Bednar tumor), myoid, atrophic, or fibrosarcomatous dermatofibrosarcoma protuberans, as well as a giant cell fibroblastoma variant.6 These tumor subtypes can exist independently or in association with one another, creating hybrid lesions that can closely mimic other entities such as pleomorphic lipoma. The spindle cells stain positively for CD34. Treatment of these tumors involves complete surgical excision or Mohs micrographic surgery; however, recurrence is common for tumors involving the head or neck.5
Superficial angiomyxoma is a slow-growing papule that most commonly appears on the trunk, head, or neck in middle-aged adults. Occasionally, patients with Carney complex also can develop lesions on the external ear or breast.7 Histologically, superficial angiomyxoma is a hypocellular tumor characterized by abundant myxoid stroma, thin blood vessels, and small spindled and stellate cells with minimal cytoplasm (Figure 2).8 Superficial angiomyxoma and pleomorphic lipoma present differently on histology; superficial angiomyxoma is not associated with nuclear atypia or pleomorphism, whereas pleomorphic lipoma characteristically contains multinucleated floretlike giant cells and pleomorphism. Frequently, there also is loss of normal PRKAR1A gene expression, which is responsible for protein kinase A regulatory subunit 1-alpha expression.8
Multinucleate cell angiohistiocytoma is a rare benign proliferation that presents with numerous red-violet asymptomatic papules that commonly appear on the upper and lower extremities of women aged 40 to 70 years. Lesions feature both a fibrohistiocytic and vascular component.9 Histologic examination commonly shows multinucleated cells with angular outlining in the superficial dermis accompanied by fibrosis and ectatic small-caliber vessels (Figure 3). Although both pleomorphic lipoma and multinucleate cell angiohistiocytoma have similar-appearing multinucleated giant cells, the latter has a proliferation of narrow vessels in thick collagen bundles and lacks an adipocytic component, which distinguishes it from the former.10 Multinucleate cell angiohistiocytoma also is characterized by a substantial number of factor XIIIa–positive fibrohistiocytic interstitial cells and vascular hyperplasia.9
Nodular fasciitis is a benign lesion involving the rapid proliferation of myofibroblasts and fibroblasts in the subcutaneous tissue and most commonly is encountered on the extremities or head and neck regions. Many cases appear at sites of prior trauma, especially in patients aged 20 to 40 years. However, in infants and children the lesions typically are found in the head and neck regions.11 Clinically, lesions present as subcutaneous nodules. Histology reveals an infiltrative and poorly circumscribed proliferation of spindled myofibroblasts associated with myxoid stroma and dense collagen depositions. The spindled cells are loosely associated, rendering a tissue culture–like appearance (Figure 4). It also is common to see erythrocyte extravasation adjacent to myxoid stroma.11 Positive stains include vimentin, smooth muscle actin, and CD68, though immunohistochemistry often is not necessary for diagnosis.12 There often is abundant mitotic activity in nodular fasciitis, especially in early lesions, and the differential diagnosis includes sarcoma. Although nodular fasciitis is mitotically active, it does not show atypical mitotic figures. Nodular fasciitis commonly harbors a gene translocation of the MYH9 gene’s promoter region to the USP6 gene’s coding region.13
- Sakhadeo U, Mundhe R, DeSouza MA, et al. Pleomorphic lipoma: a gentle giant of pathology. J Cytol. 2015;32:201-203. doi:10.4103 /0970-9371.168904
- Shmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma. a clinicopathologic analysis of 48 cases. Cancer. 1981;47:126-133.
- Azzopardi JG, Iocco J, Salm R. Pleomorphic lipoma: a tumour simulating liposarcoma. Histopathology. 1983;7:511-523. doi:10.1111/j.1365-2559.1983.tb02264.x
- Jäger M, Winkelmann R, Eichler K, et al. Pleomorphic lipoma. J Dtsch Dermatol Ges. 2018;16:208-210. doi:10.1111/ddg.13422
- Allen A, Ahn C, Sangüeza OP. Dermatofibrosarcoma protuberans. Dermatol Clin. 2019;37:483-488. doi:10.1016/j.det.2019.05.006
- Socoliuc C, Zurac S, Andrei R, et al. Multiple histological subtypes of dermatofibrosarcoma protuberans occurring in the same tumor. Rom J Intern Med. 2015;53:79-88. doi:10.1515/rjim-2015-0011
- Abarzúa-Araya A, Lallas A, Piana S, et al. Superficial angiomyxoma of the skin. Dermatol Pract Concept. 2016;6:47-49. doi:10.5826 /dpc.0603a09
- Hornick J. Practical Soft Tissue Pathology A Diagnostic Approach. 2nd ed. Elsevier Health Sciences; 2017.
- Rato M, Monteiro AF, Parente J, et al. Case for diagnosis. multinucleated cell angiohistiocytoma. An Bras Dermatol. 2018;93:291-293. doi:10.1590 /abd1806-4841.20186821
- Grgurich E, Quinn K, Oram C, et al. Multinucleate cell angiohistiocytoma: case report and literature review. J Cutan Pathol. 2019;46:59-61. doi:10.1111/cup.13361
- Zuber TJ, Finley JL. Nodular fasciitis. South Med J. 1994;87:842-844. doi:10.1097/00007611-199408000-00020
- Yver CM, Husson MA, Friedman O. Pathology clinic: nodular fasciitis involving the external ear [published online March 18, 2021]. Ear Nose Throat J. doi:10.1177/01455613211001958
- Erickson-Johnson M, Chou M, Evers B, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433. https://doi.org/10.1038 /labinvest.2011.118
The Diagnosis: Pleomorphic Lipoma
Pleomorphic lipoma is a rare, benign, adipocytic neoplasm that presents in the subcutaneous tissues of the upper shoulder, back, or neck. It predominantly affects men aged 50 to 70 years. Most lesions are situated in the subcutaneous tissues; few cases of intramuscular and retroperitoneal tumors have been reported.1 Clinically, pleomorphic lipomas present as painless, well-circumscribed lesions of the subcutaneous tissue that often resemble a lipoma or occasionally may be mistaken for liposarcoma. Histopathologic examination of ordinary lipomas reveals uniform mature adipocytes. However, pleomorphic lipomas consist of a mixture of multinucleated floretlike giant cells, variable-sized adipocytes, and fibrous tissue (ropy collagen bundles) with some myxoid and spindled areas.1,2 The most characteristic histologic feature of pleomorphic lipoma is multinucleated floretlike giant cells. The nuclei of these giant cells appear hyperchromatic, enlarged, and disposed to the periphery of the cell in a circular pattern. Additionally, tumors frequently contain excess mature dense collagen bundles that are strongly refractile in polarized light. Numerous mast cells are present. Atypical lipoblasts and capillary networks commonly are not visible in pleomorphic lipoma.3 The spindle cells express CD34 on immunohistochemistry. Loss of Rb-1 expression is typical.4
Dermatofibrosarcoma protuberans is a slow-growing soft tissue sarcoma that commonly begins as a pink or violet plaque on the trunk or upper limbs. Involvement of the head or neck accounts for only 10% to 15% of cases.5 This tumor has low metastatic potential but is highly infiltrative of surrounding tissues. It is associated with a translocation between chromosomes 22 and 17, leading to the fusion of the platelet-derived growth factor subunit β, PDGFB, and collagen type 1α1, COL1A1, genes.5 Clinically, patients often report that the lesion was present for several years prior to presentation with general stability in size and shape. Eventually, untreated lesions progress to become nodules or tumors and may even bleed or ulcerate. Histology reveals a storiform spindle cell proliferation throughout the dermis with infiltration into subcutaneous fat, commonly appearing in a honeycomblike pattern (Figure 1). Numerous histologic variants exist, including myxoid, sclerosing, pigmented (Bednar tumor), myoid, atrophic, or fibrosarcomatous dermatofibrosarcoma protuberans, as well as a giant cell fibroblastoma variant.6 These tumor subtypes can exist independently or in association with one another, creating hybrid lesions that can closely mimic other entities such as pleomorphic lipoma. The spindle cells stain positively for CD34. Treatment of these tumors involves complete surgical excision or Mohs micrographic surgery; however, recurrence is common for tumors involving the head or neck.5
Superficial angiomyxoma is a slow-growing papule that most commonly appears on the trunk, head, or neck in middle-aged adults. Occasionally, patients with Carney complex also can develop lesions on the external ear or breast.7 Histologically, superficial angiomyxoma is a hypocellular tumor characterized by abundant myxoid stroma, thin blood vessels, and small spindled and stellate cells with minimal cytoplasm (Figure 2).8 Superficial angiomyxoma and pleomorphic lipoma present differently on histology; superficial angiomyxoma is not associated with nuclear atypia or pleomorphism, whereas pleomorphic lipoma characteristically contains multinucleated floretlike giant cells and pleomorphism. Frequently, there also is loss of normal PRKAR1A gene expression, which is responsible for protein kinase A regulatory subunit 1-alpha expression.8
Multinucleate cell angiohistiocytoma is a rare benign proliferation that presents with numerous red-violet asymptomatic papules that commonly appear on the upper and lower extremities of women aged 40 to 70 years. Lesions feature both a fibrohistiocytic and vascular component.9 Histologic examination commonly shows multinucleated cells with angular outlining in the superficial dermis accompanied by fibrosis and ectatic small-caliber vessels (Figure 3). Although both pleomorphic lipoma and multinucleate cell angiohistiocytoma have similar-appearing multinucleated giant cells, the latter has a proliferation of narrow vessels in thick collagen bundles and lacks an adipocytic component, which distinguishes it from the former.10 Multinucleate cell angiohistiocytoma also is characterized by a substantial number of factor XIIIa–positive fibrohistiocytic interstitial cells and vascular hyperplasia.9
Nodular fasciitis is a benign lesion involving the rapid proliferation of myofibroblasts and fibroblasts in the subcutaneous tissue and most commonly is encountered on the extremities or head and neck regions. Many cases appear at sites of prior trauma, especially in patients aged 20 to 40 years. However, in infants and children the lesions typically are found in the head and neck regions.11 Clinically, lesions present as subcutaneous nodules. Histology reveals an infiltrative and poorly circumscribed proliferation of spindled myofibroblasts associated with myxoid stroma and dense collagen depositions. The spindled cells are loosely associated, rendering a tissue culture–like appearance (Figure 4). It also is common to see erythrocyte extravasation adjacent to myxoid stroma.11 Positive stains include vimentin, smooth muscle actin, and CD68, though immunohistochemistry often is not necessary for diagnosis.12 There often is abundant mitotic activity in nodular fasciitis, especially in early lesions, and the differential diagnosis includes sarcoma. Although nodular fasciitis is mitotically active, it does not show atypical mitotic figures. Nodular fasciitis commonly harbors a gene translocation of the MYH9 gene’s promoter region to the USP6 gene’s coding region.13
The Diagnosis: Pleomorphic Lipoma
Pleomorphic lipoma is a rare, benign, adipocytic neoplasm that presents in the subcutaneous tissues of the upper shoulder, back, or neck. It predominantly affects men aged 50 to 70 years. Most lesions are situated in the subcutaneous tissues; few cases of intramuscular and retroperitoneal tumors have been reported.1 Clinically, pleomorphic lipomas present as painless, well-circumscribed lesions of the subcutaneous tissue that often resemble a lipoma or occasionally may be mistaken for liposarcoma. Histopathologic examination of ordinary lipomas reveals uniform mature adipocytes. However, pleomorphic lipomas consist of a mixture of multinucleated floretlike giant cells, variable-sized adipocytes, and fibrous tissue (ropy collagen bundles) with some myxoid and spindled areas.1,2 The most characteristic histologic feature of pleomorphic lipoma is multinucleated floretlike giant cells. The nuclei of these giant cells appear hyperchromatic, enlarged, and disposed to the periphery of the cell in a circular pattern. Additionally, tumors frequently contain excess mature dense collagen bundles that are strongly refractile in polarized light. Numerous mast cells are present. Atypical lipoblasts and capillary networks commonly are not visible in pleomorphic lipoma.3 The spindle cells express CD34 on immunohistochemistry. Loss of Rb-1 expression is typical.4
Dermatofibrosarcoma protuberans is a slow-growing soft tissue sarcoma that commonly begins as a pink or violet plaque on the trunk or upper limbs. Involvement of the head or neck accounts for only 10% to 15% of cases.5 This tumor has low metastatic potential but is highly infiltrative of surrounding tissues. It is associated with a translocation between chromosomes 22 and 17, leading to the fusion of the platelet-derived growth factor subunit β, PDGFB, and collagen type 1α1, COL1A1, genes.5 Clinically, patients often report that the lesion was present for several years prior to presentation with general stability in size and shape. Eventually, untreated lesions progress to become nodules or tumors and may even bleed or ulcerate. Histology reveals a storiform spindle cell proliferation throughout the dermis with infiltration into subcutaneous fat, commonly appearing in a honeycomblike pattern (Figure 1). Numerous histologic variants exist, including myxoid, sclerosing, pigmented (Bednar tumor), myoid, atrophic, or fibrosarcomatous dermatofibrosarcoma protuberans, as well as a giant cell fibroblastoma variant.6 These tumor subtypes can exist independently or in association with one another, creating hybrid lesions that can closely mimic other entities such as pleomorphic lipoma. The spindle cells stain positively for CD34. Treatment of these tumors involves complete surgical excision or Mohs micrographic surgery; however, recurrence is common for tumors involving the head or neck.5
Superficial angiomyxoma is a slow-growing papule that most commonly appears on the trunk, head, or neck in middle-aged adults. Occasionally, patients with Carney complex also can develop lesions on the external ear or breast.7 Histologically, superficial angiomyxoma is a hypocellular tumor characterized by abundant myxoid stroma, thin blood vessels, and small spindled and stellate cells with minimal cytoplasm (Figure 2).8 Superficial angiomyxoma and pleomorphic lipoma present differently on histology; superficial angiomyxoma is not associated with nuclear atypia or pleomorphism, whereas pleomorphic lipoma characteristically contains multinucleated floretlike giant cells and pleomorphism. Frequently, there also is loss of normal PRKAR1A gene expression, which is responsible for protein kinase A regulatory subunit 1-alpha expression.8
Multinucleate cell angiohistiocytoma is a rare benign proliferation that presents with numerous red-violet asymptomatic papules that commonly appear on the upper and lower extremities of women aged 40 to 70 years. Lesions feature both a fibrohistiocytic and vascular component.9 Histologic examination commonly shows multinucleated cells with angular outlining in the superficial dermis accompanied by fibrosis and ectatic small-caliber vessels (Figure 3). Although both pleomorphic lipoma and multinucleate cell angiohistiocytoma have similar-appearing multinucleated giant cells, the latter has a proliferation of narrow vessels in thick collagen bundles and lacks an adipocytic component, which distinguishes it from the former.10 Multinucleate cell angiohistiocytoma also is characterized by a substantial number of factor XIIIa–positive fibrohistiocytic interstitial cells and vascular hyperplasia.9
Nodular fasciitis is a benign lesion involving the rapid proliferation of myofibroblasts and fibroblasts in the subcutaneous tissue and most commonly is encountered on the extremities or head and neck regions. Many cases appear at sites of prior trauma, especially in patients aged 20 to 40 years. However, in infants and children the lesions typically are found in the head and neck regions.11 Clinically, lesions present as subcutaneous nodules. Histology reveals an infiltrative and poorly circumscribed proliferation of spindled myofibroblasts associated with myxoid stroma and dense collagen depositions. The spindled cells are loosely associated, rendering a tissue culture–like appearance (Figure 4). It also is common to see erythrocyte extravasation adjacent to myxoid stroma.11 Positive stains include vimentin, smooth muscle actin, and CD68, though immunohistochemistry often is not necessary for diagnosis.12 There often is abundant mitotic activity in nodular fasciitis, especially in early lesions, and the differential diagnosis includes sarcoma. Although nodular fasciitis is mitotically active, it does not show atypical mitotic figures. Nodular fasciitis commonly harbors a gene translocation of the MYH9 gene’s promoter region to the USP6 gene’s coding region.13
- Sakhadeo U, Mundhe R, DeSouza MA, et al. Pleomorphic lipoma: a gentle giant of pathology. J Cytol. 2015;32:201-203. doi:10.4103 /0970-9371.168904
- Shmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma. a clinicopathologic analysis of 48 cases. Cancer. 1981;47:126-133.
- Azzopardi JG, Iocco J, Salm R. Pleomorphic lipoma: a tumour simulating liposarcoma. Histopathology. 1983;7:511-523. doi:10.1111/j.1365-2559.1983.tb02264.x
- Jäger M, Winkelmann R, Eichler K, et al. Pleomorphic lipoma. J Dtsch Dermatol Ges. 2018;16:208-210. doi:10.1111/ddg.13422
- Allen A, Ahn C, Sangüeza OP. Dermatofibrosarcoma protuberans. Dermatol Clin. 2019;37:483-488. doi:10.1016/j.det.2019.05.006
- Socoliuc C, Zurac S, Andrei R, et al. Multiple histological subtypes of dermatofibrosarcoma protuberans occurring in the same tumor. Rom J Intern Med. 2015;53:79-88. doi:10.1515/rjim-2015-0011
- Abarzúa-Araya A, Lallas A, Piana S, et al. Superficial angiomyxoma of the skin. Dermatol Pract Concept. 2016;6:47-49. doi:10.5826 /dpc.0603a09
- Hornick J. Practical Soft Tissue Pathology A Diagnostic Approach. 2nd ed. Elsevier Health Sciences; 2017.
- Rato M, Monteiro AF, Parente J, et al. Case for diagnosis. multinucleated cell angiohistiocytoma. An Bras Dermatol. 2018;93:291-293. doi:10.1590 /abd1806-4841.20186821
- Grgurich E, Quinn K, Oram C, et al. Multinucleate cell angiohistiocytoma: case report and literature review. J Cutan Pathol. 2019;46:59-61. doi:10.1111/cup.13361
- Zuber TJ, Finley JL. Nodular fasciitis. South Med J. 1994;87:842-844. doi:10.1097/00007611-199408000-00020
- Yver CM, Husson MA, Friedman O. Pathology clinic: nodular fasciitis involving the external ear [published online March 18, 2021]. Ear Nose Throat J. doi:10.1177/01455613211001958
- Erickson-Johnson M, Chou M, Evers B, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433. https://doi.org/10.1038 /labinvest.2011.118
- Sakhadeo U, Mundhe R, DeSouza MA, et al. Pleomorphic lipoma: a gentle giant of pathology. J Cytol. 2015;32:201-203. doi:10.4103 /0970-9371.168904
- Shmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma. a clinicopathologic analysis of 48 cases. Cancer. 1981;47:126-133.
- Azzopardi JG, Iocco J, Salm R. Pleomorphic lipoma: a tumour simulating liposarcoma. Histopathology. 1983;7:511-523. doi:10.1111/j.1365-2559.1983.tb02264.x
- Jäger M, Winkelmann R, Eichler K, et al. Pleomorphic lipoma. J Dtsch Dermatol Ges. 2018;16:208-210. doi:10.1111/ddg.13422
- Allen A, Ahn C, Sangüeza OP. Dermatofibrosarcoma protuberans. Dermatol Clin. 2019;37:483-488. doi:10.1016/j.det.2019.05.006
- Socoliuc C, Zurac S, Andrei R, et al. Multiple histological subtypes of dermatofibrosarcoma protuberans occurring in the same tumor. Rom J Intern Med. 2015;53:79-88. doi:10.1515/rjim-2015-0011
- Abarzúa-Araya A, Lallas A, Piana S, et al. Superficial angiomyxoma of the skin. Dermatol Pract Concept. 2016;6:47-49. doi:10.5826 /dpc.0603a09
- Hornick J. Practical Soft Tissue Pathology A Diagnostic Approach. 2nd ed. Elsevier Health Sciences; 2017.
- Rato M, Monteiro AF, Parente J, et al. Case for diagnosis. multinucleated cell angiohistiocytoma. An Bras Dermatol. 2018;93:291-293. doi:10.1590 /abd1806-4841.20186821
- Grgurich E, Quinn K, Oram C, et al. Multinucleate cell angiohistiocytoma: case report and literature review. J Cutan Pathol. 2019;46:59-61. doi:10.1111/cup.13361
- Zuber TJ, Finley JL. Nodular fasciitis. South Med J. 1994;87:842-844. doi:10.1097/00007611-199408000-00020
- Yver CM, Husson MA, Friedman O. Pathology clinic: nodular fasciitis involving the external ear [published online March 18, 2021]. Ear Nose Throat J. doi:10.1177/01455613211001958
- Erickson-Johnson M, Chou M, Evers B, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-1433. https://doi.org/10.1038 /labinvest.2011.118
An otherwise healthy 56-year-old man with a family history of lymphoma presented with a raised lesion on the postauricular neck. He first noticed the nodule 3 months prior and was unsure if it was still getting larger. It was predominantly asymptomatic. Physical examination revealed a 1.5×1.5-cm, mobile, subcutaneous nodule. An incisional biopsy was performed and submitted for histologic evaluation.
Disparities in Melanoma Demographics, Tumor Stage, and Metastases in Hispanic and Latino Patients: A Retrospective Study
To the Editor:
Melanoma is an aggressive form of skin cancer with a high rate of metastasis and poor prognosis.1 Historically, Hispanic and/or Latino patients have presented with more advanced-stage melanomas and have lower survival rates compared with non-Hispanic and/or non-Latino White patients.2 In this study, we evaluated recent data from the last decade to investigate if disparities in melanoma tumor stage at diagnosis and risk for metastases continue to exist in the Hispanic and/or Latino population.
We conducted a retrospective review of melanoma patients at 2 major medical centers in Los Angeles, California—Keck Medicine of USC and Los Angeles County-USC Medical Center—from January 2010 to January 2020. The data collected from electronic medical records included age at melanoma diagnosis, sex, race and ethnicity, insurance type, Breslow depth of lesion, presence of ulceration, and presence of lymph node or distant metastases. Melanoma tumor stage was determined using the American Joint Committee on Cancer classification. Patients who self-reported their ethnicity as not Hispanic and/or Latino were designated to this group regardless of their reported race. Those patients who reported their ethnicity as not Hispanic and/or Latino and reported their race as White were designated as non-Hispanic and/or non-Latino White. This study was approved by the institutional review board of the University of Southern California (Los Angeles). Data analysis was performed using the Pearson χ2 test, Fisher exact test, and Wilcoxon rank sum test. Statistical significance was determined at P<.05.
The final cohort of patients included 79 Hispanic and/or Latino patients and 402 non-Hispanic and/or non-Latino White patients. The median age for the Hispanic and/or Latino group was 54 years and 64 years for the non-Hispanic and/or non-Latino White group (P<.001). There was a greater percentage of females in the Hispanic and/or Latino group compared with the non-Hispanic and/or non-Latino White group (53.2% vs 34.6%)(P=.002). Hispanic and/or Latino patients presented with more advanced tumor stage melanomas (T3: 15.2%; T4: 21.5%) compared with non-Hispanic and/or non-Latino White patients (T3: 8.0%; T4: 10.7%)(P=.004). Furthermore, Hispanic and/or Latino patients had higher rates of lymph node metastases compared with non-Hispanic and/or non-Latino White patients (20.3% vs 7.7% [P<.001]) and higher rates of distant metastases (12.7% vs 5.2% [P=.014])(Table 1). The majority of Hispanic and/or Latino patients had Medicaid (39.2%), while most non-Hispanic and/or non-Latino White patients had a preferred provider organization insurance plan (37.3%) or Medicare (34.3%)(P<.001)(Table 2).
This retrospective study analyzing nearly 10 years of recent melanoma data found that disparities in melanoma diagnosis and treatment continue to exist among Hispanic and/or Latino patients. Compared to non-Hispanic and/or non-Latino White patients, Hispanic and/or Latino patients were diagnosed with melanoma at a younger age and the proportion of females with melanoma was higher. Cormier et al2 also reported that Hispanic patients were younger at melanoma diagnosis, and females represented a larger majority of patients in the Hispanic population compared with the White population. Hispanic and/or Latino patients in our study had more advanced melanoma tumor stage at diagnosis and a higher risk of lymph node and distant metastases, similar to findings reported by Koblinksi et al.3
Our retrospective cohort study demonstrated that the demographics of Hispanic and/or Latino patients with melanoma differ from non-Hispanic and/or non-Latino White patients, specifically with a greater proportion of younger and female patients in the Hispanic and/or Latino population. We also found that Hispanic and/or Latino patients continue to experience worse melanoma outcomes compared with non-Hispanic and/or non-Latino White patients. Further studies are needed to investigate the etiologies behind these health care disparities and potential interventions to address them. In addition, there needs to be increased awareness of the risk for melanoma in Hispanic and/or Latino patients among both health care providers and patients.
Limitations of this study included a smaller sample size of patients from one geographic region. The retrospective design of this study also increased the risk for selection bias, as some of the patients may have had incomplete records or were lost to follow-up. Therefore, the study cohort may not be representative of the general population. Additionally, patients’ skin types could not be determined using standardized tools such as the Fitzpatrick scale, thus we could not assess how patient skin type may have affected melanoma outcomes.
- Aggarwal P, Knabel P, Fleischer AB. United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019. J Am Acad Dermatol. 2021;85:388-395. doi:10.1016/j.jaad.2021.03.109
- Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907. doi:10.1001/archinte.166.17.1907
- Koblinski JE, Maykowski P, Zeitouni NC. Disparities in melanoma stage at diagnosis in Arizona: a 10-year Arizona Cancer Registry study. J Am Acad Dermatol. 2021;84:1776-1779. doi:10.1016/j.jaad.2021.02.045
To the Editor:
Melanoma is an aggressive form of skin cancer with a high rate of metastasis and poor prognosis.1 Historically, Hispanic and/or Latino patients have presented with more advanced-stage melanomas and have lower survival rates compared with non-Hispanic and/or non-Latino White patients.2 In this study, we evaluated recent data from the last decade to investigate if disparities in melanoma tumor stage at diagnosis and risk for metastases continue to exist in the Hispanic and/or Latino population.
We conducted a retrospective review of melanoma patients at 2 major medical centers in Los Angeles, California—Keck Medicine of USC and Los Angeles County-USC Medical Center—from January 2010 to January 2020. The data collected from electronic medical records included age at melanoma diagnosis, sex, race and ethnicity, insurance type, Breslow depth of lesion, presence of ulceration, and presence of lymph node or distant metastases. Melanoma tumor stage was determined using the American Joint Committee on Cancer classification. Patients who self-reported their ethnicity as not Hispanic and/or Latino were designated to this group regardless of their reported race. Those patients who reported their ethnicity as not Hispanic and/or Latino and reported their race as White were designated as non-Hispanic and/or non-Latino White. This study was approved by the institutional review board of the University of Southern California (Los Angeles). Data analysis was performed using the Pearson χ2 test, Fisher exact test, and Wilcoxon rank sum test. Statistical significance was determined at P<.05.
The final cohort of patients included 79 Hispanic and/or Latino patients and 402 non-Hispanic and/or non-Latino White patients. The median age for the Hispanic and/or Latino group was 54 years and 64 years for the non-Hispanic and/or non-Latino White group (P<.001). There was a greater percentage of females in the Hispanic and/or Latino group compared with the non-Hispanic and/or non-Latino White group (53.2% vs 34.6%)(P=.002). Hispanic and/or Latino patients presented with more advanced tumor stage melanomas (T3: 15.2%; T4: 21.5%) compared with non-Hispanic and/or non-Latino White patients (T3: 8.0%; T4: 10.7%)(P=.004). Furthermore, Hispanic and/or Latino patients had higher rates of lymph node metastases compared with non-Hispanic and/or non-Latino White patients (20.3% vs 7.7% [P<.001]) and higher rates of distant metastases (12.7% vs 5.2% [P=.014])(Table 1). The majority of Hispanic and/or Latino patients had Medicaid (39.2%), while most non-Hispanic and/or non-Latino White patients had a preferred provider organization insurance plan (37.3%) or Medicare (34.3%)(P<.001)(Table 2).
This retrospective study analyzing nearly 10 years of recent melanoma data found that disparities in melanoma diagnosis and treatment continue to exist among Hispanic and/or Latino patients. Compared to non-Hispanic and/or non-Latino White patients, Hispanic and/or Latino patients were diagnosed with melanoma at a younger age and the proportion of females with melanoma was higher. Cormier et al2 also reported that Hispanic patients were younger at melanoma diagnosis, and females represented a larger majority of patients in the Hispanic population compared with the White population. Hispanic and/or Latino patients in our study had more advanced melanoma tumor stage at diagnosis and a higher risk of lymph node and distant metastases, similar to findings reported by Koblinksi et al.3
Our retrospective cohort study demonstrated that the demographics of Hispanic and/or Latino patients with melanoma differ from non-Hispanic and/or non-Latino White patients, specifically with a greater proportion of younger and female patients in the Hispanic and/or Latino population. We also found that Hispanic and/or Latino patients continue to experience worse melanoma outcomes compared with non-Hispanic and/or non-Latino White patients. Further studies are needed to investigate the etiologies behind these health care disparities and potential interventions to address them. In addition, there needs to be increased awareness of the risk for melanoma in Hispanic and/or Latino patients among both health care providers and patients.
Limitations of this study included a smaller sample size of patients from one geographic region. The retrospective design of this study also increased the risk for selection bias, as some of the patients may have had incomplete records or were lost to follow-up. Therefore, the study cohort may not be representative of the general population. Additionally, patients’ skin types could not be determined using standardized tools such as the Fitzpatrick scale, thus we could not assess how patient skin type may have affected melanoma outcomes.
To the Editor:
Melanoma is an aggressive form of skin cancer with a high rate of metastasis and poor prognosis.1 Historically, Hispanic and/or Latino patients have presented with more advanced-stage melanomas and have lower survival rates compared with non-Hispanic and/or non-Latino White patients.2 In this study, we evaluated recent data from the last decade to investigate if disparities in melanoma tumor stage at diagnosis and risk for metastases continue to exist in the Hispanic and/or Latino population.
We conducted a retrospective review of melanoma patients at 2 major medical centers in Los Angeles, California—Keck Medicine of USC and Los Angeles County-USC Medical Center—from January 2010 to January 2020. The data collected from electronic medical records included age at melanoma diagnosis, sex, race and ethnicity, insurance type, Breslow depth of lesion, presence of ulceration, and presence of lymph node or distant metastases. Melanoma tumor stage was determined using the American Joint Committee on Cancer classification. Patients who self-reported their ethnicity as not Hispanic and/or Latino were designated to this group regardless of their reported race. Those patients who reported their ethnicity as not Hispanic and/or Latino and reported their race as White were designated as non-Hispanic and/or non-Latino White. This study was approved by the institutional review board of the University of Southern California (Los Angeles). Data analysis was performed using the Pearson χ2 test, Fisher exact test, and Wilcoxon rank sum test. Statistical significance was determined at P<.05.
The final cohort of patients included 79 Hispanic and/or Latino patients and 402 non-Hispanic and/or non-Latino White patients. The median age for the Hispanic and/or Latino group was 54 years and 64 years for the non-Hispanic and/or non-Latino White group (P<.001). There was a greater percentage of females in the Hispanic and/or Latino group compared with the non-Hispanic and/or non-Latino White group (53.2% vs 34.6%)(P=.002). Hispanic and/or Latino patients presented with more advanced tumor stage melanomas (T3: 15.2%; T4: 21.5%) compared with non-Hispanic and/or non-Latino White patients (T3: 8.0%; T4: 10.7%)(P=.004). Furthermore, Hispanic and/or Latino patients had higher rates of lymph node metastases compared with non-Hispanic and/or non-Latino White patients (20.3% vs 7.7% [P<.001]) and higher rates of distant metastases (12.7% vs 5.2% [P=.014])(Table 1). The majority of Hispanic and/or Latino patients had Medicaid (39.2%), while most non-Hispanic and/or non-Latino White patients had a preferred provider organization insurance plan (37.3%) or Medicare (34.3%)(P<.001)(Table 2).
This retrospective study analyzing nearly 10 years of recent melanoma data found that disparities in melanoma diagnosis and treatment continue to exist among Hispanic and/or Latino patients. Compared to non-Hispanic and/or non-Latino White patients, Hispanic and/or Latino patients were diagnosed with melanoma at a younger age and the proportion of females with melanoma was higher. Cormier et al2 also reported that Hispanic patients were younger at melanoma diagnosis, and females represented a larger majority of patients in the Hispanic population compared with the White population. Hispanic and/or Latino patients in our study had more advanced melanoma tumor stage at diagnosis and a higher risk of lymph node and distant metastases, similar to findings reported by Koblinksi et al.3
Our retrospective cohort study demonstrated that the demographics of Hispanic and/or Latino patients with melanoma differ from non-Hispanic and/or non-Latino White patients, specifically with a greater proportion of younger and female patients in the Hispanic and/or Latino population. We also found that Hispanic and/or Latino patients continue to experience worse melanoma outcomes compared with non-Hispanic and/or non-Latino White patients. Further studies are needed to investigate the etiologies behind these health care disparities and potential interventions to address them. In addition, there needs to be increased awareness of the risk for melanoma in Hispanic and/or Latino patients among both health care providers and patients.
Limitations of this study included a smaller sample size of patients from one geographic region. The retrospective design of this study also increased the risk for selection bias, as some of the patients may have had incomplete records or were lost to follow-up. Therefore, the study cohort may not be representative of the general population. Additionally, patients’ skin types could not be determined using standardized tools such as the Fitzpatrick scale, thus we could not assess how patient skin type may have affected melanoma outcomes.
- Aggarwal P, Knabel P, Fleischer AB. United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019. J Am Acad Dermatol. 2021;85:388-395. doi:10.1016/j.jaad.2021.03.109
- Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907. doi:10.1001/archinte.166.17.1907
- Koblinski JE, Maykowski P, Zeitouni NC. Disparities in melanoma stage at diagnosis in Arizona: a 10-year Arizona Cancer Registry study. J Am Acad Dermatol. 2021;84:1776-1779. doi:10.1016/j.jaad.2021.02.045
- Aggarwal P, Knabel P, Fleischer AB. United States burden of melanoma and non-melanoma skin cancer from 1990 to 2019. J Am Acad Dermatol. 2021;85:388-395. doi:10.1016/j.jaad.2021.03.109
- Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907. doi:10.1001/archinte.166.17.1907
- Koblinski JE, Maykowski P, Zeitouni NC. Disparities in melanoma stage at diagnosis in Arizona: a 10-year Arizona Cancer Registry study. J Am Acad Dermatol. 2021;84:1776-1779. doi:10.1016/j.jaad.2021.02.045
Practice Points
- Hispanic and/or Latino patients often present with more advanced-stage melanomas and have decreased survival rates compared with non-Hispanic and/or non-Latino White patients.
- More education and awareness on the risk for melanoma as well as sun-protective behaviors in the Hispanic and/or Latino population is needed among both health care providers and patients to prevent diagnosis of melanoma in later stages and improve outcomes.
Botanical Briefs: Handling the Heat From Capsicum Peppers
Cutaneous Manifestations
Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.1
Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.2Capsicum peppers also have induced allergic contact dermatitis in a food production worker.3
Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.4
Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.7 Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.
Obtaining Relief
Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.8 Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.9
Identifying Features and Plant Facts
The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000
Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.12 Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.
Irritant Chemicals
Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.13 Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.14 Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.15
Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.1 Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.
Medicinal Use
On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,5 postherpetic neuralgia,6 psoriasis,16 and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,17 fibromyalgia,18 migraines,14 cluster headaches,9 and HIV-associated distal sensory neuropathy.5
Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.19 The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.11 Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.20,21
Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.22 The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.23
Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.27 Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.
Final Thoughts
Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.
- Otang WM, Grierson DS, Afolayan AJ. A survey of plants responsible for causing irritant contact dermatitis in the Amathole district, Eastern Cape, South Africa. J Ethnopharmacol. 2014;157:274-284. doi:10.1016/j.jep.2014.10.002
- Weinberg RB. Hunan hand. N Engl J Med. 1981;305:1020.
- Lambrecht C, Goossens A. Occupational allergic contact dermatitis caused by capsicum. Contact Dermatitis. 2015;72:252-253. doi:10.1111/cod.12345
- Haar RJ, Iacopino V, Ranadive N, et al. Health impacts of chemical irritants used for crowd control: a systematic review of the injuries and deaths caused by tear gas and pepper spray. BMC Public Health. 2017;17:831. doi:10.1186/s12889-017-4814-6
- Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18:42-53. doi:10.1016/j.jpain.2016.09.008
- Yong YL, Tan LT-H, Ming LC, et al. The effectiveness and safety of topical capsaicin in postherpetic neuralgia: a systematic review and meta-analysis. Front Pharmacol. 2016;7:538. doi:10.3389/fphar.2016.00538
- Firoz EF, Levin JM, Hartman RD, et al. Lip plumper contact urticaria. J Am Acad Dermatol. 2009;60:861-863. doi:10.1016/j.jaad.2008.09.028
- Jones LA, Tandberg D, Troutman WG. Household treatment for “chile burns” of the hands. J Toxicol Clin Toxicol. 1987;25:483-491. doi:10.3109/15563658708992651
- Saxena AK, Mandhyan R. Multimodal approach for the management of Hunan hand syndrome: a case report. Pain Pract. 2013;13:227-230. doi:10.1111/j.1533-2500.2012.00567.x
- Cordell GA, Araujo OE. Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother. 1993;27:330-336. doi:10.1177/106002809302700316
- Baranidharan G, Das S, Bhaskar A. A review of the high-concentration capsaicin patch and experience in its use in the management of neuropathic pain. Ther Adv Neurol Disord. 2013;6:287-297. doi:10.1177/1756285613496862
- Carrizo García C, Barfuss MHJ, Sehr EM, et al. Phylogenetic relationships, diversification and expansion of chili peppers (Capsicum, Solanaceae). Ann Bot. 2016;118:35-51. doi:10.1093/aob/mcw079
- Basharat S, Gilani SA, Iftikhar F, et al. Capsaicin: plants of the genus Capsicum and positive effect of Oriental spice on skin health. Skin Pharmacol Physiol. 2020;33:331-341. doi:10.1159/000512196
- Hopps JJ, Dunn WR, Randall MD. Vasorelaxation to capsaicin and its effects on calcium influx in arteries. Eur J Pharmacol. 2012;681:88-93. doi:10.1016/j.ejphar.2012.02.019
- Burks TF, Buck SH, Miller MS. Mechanisms of depletion of substance P by capsaicin. Fed Proc. 1985;44:2531-2534.
- Ellis CN, Berberian B, Sulica VI, et al. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol. 1993;29:438-442. doi:10.1016/0190-9622(93)70208-b
- Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg. 1992;74:375-377. doi:10.1213/00000539-199203000-00011
- Casanueva B, Rodero B, Quintial C, et al. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int. 2013;33:2665-2670. doi:10.1007/s00296-012-2490-5
- Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40:847-873. doi:10.1177/0192623312444471
- Jones IA, Togashi R, Wilson ML, et al. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15:77-90. doi:10.1038/s41584-018-0123-4
- Campbell JN, Stevens R, Hanson P, et al. Injectable capsaicin for the management of pain due to osteoarthritis. Molecules. 2021;26:778.
- Maji AK, Banerji P. Phytochemistry and gastrointestinal benefits of the medicinal spice, Capsicum annum L. (chilli): a review. J Complement Integr Med. 2016;13:97-122. doi:10.1515jcim-2015-0037
- Baenas N, Belovié M, Ilie N, et al. Industrial use of pepper (Capsicum annum L.) derived products: technological benefits and biological advantages. Food Chem. 2019;274:872-885. doi:10.1016/j.foodchem.2018.09.047
- Lin RJ, Wu IJ, Hong JY, et al. Capsaicin-induced TRIB3 upregulation promotes apoptosis in cancer cells. Cancer Manag Res. 2018;10:4237-4248. doi:10.2147/CMAR.S162383
- Jung MY, Kang HJ, Moon A. Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett. 2001;165:139-145. doi:10.1016/s0304-3835(01)00426-8
- Ito K, Nakazato T, Yamato K, et al. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004;64:1071-1078. doi:10.1158/0008-5472.can-03-1670
- Báez S, Tsuchiya Y, Calvo A, et al. Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. World J Gastroenterol. 2010;16:372-378. doi:10.3748/wjg.v16.i3.372
Cutaneous Manifestations
Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.1
Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.2Capsicum peppers also have induced allergic contact dermatitis in a food production worker.3
Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.4
Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.7 Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.
Obtaining Relief
Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.8 Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.9
Identifying Features and Plant Facts
The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000
Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.12 Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.
Irritant Chemicals
Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.13 Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.14 Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.15
Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.1 Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.
Medicinal Use
On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,5 postherpetic neuralgia,6 psoriasis,16 and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,17 fibromyalgia,18 migraines,14 cluster headaches,9 and HIV-associated distal sensory neuropathy.5
Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.19 The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.11 Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.20,21
Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.22 The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.23
Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.27 Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.
Final Thoughts
Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.
Cutaneous Manifestations
Capsicum peppers are used worldwide in preparing spicy dishes. Their active ingredient—capsaicin—is used as a topical medicine to treat localized pain. Capsicum peppers can cause irritant contact dermatitis with symptoms of erythema, cutaneous burning, and itch.1
Irritant contact dermatitis is a common occupational skin disorder. Many cooks have experienced the sting of a chili pepper after contact with the hands or eyes. Cases of chronic exposure to Capsicum peppers with persistent burning and pain have been called Hunan hand syndrome.2Capsicum peppers also have induced allergic contact dermatitis in a food production worker.3
Capsicum peppers also are used in pepper spray, tear gas, and animal repellents because of their stinging properties. These agents usually cause cutaneous tingling and burning that soon resolves; however, a review of 31 studies showed that crowd-control methods with Capsicum-containing tear gas and pepper spray can cause moderate to severe skin damage such as a persistent skin rash or erythema, or even first-, second-, or third-degree burns.4
Topical application of capsaicin isolate is meant to cause burning and deplete local neuropeptides, with a cutaneous reaction that ranges from mild to intolerable.5,6 Capsaicin also is found in other products. In one published case report, a 3-year-old boy broke out in facial urticaria when his mother kissed him on the cheek after she applied lip plumper containing capsaicin to her lips.7 Dermatologists should consider capsaicin an active ingredient that can irritate the skin in the garden, in the kitchen, and in topical products.
Obtaining Relief
Capsaicin-induced dermatitis can be relieved by washing the area with soap, detergent, baking soda, or oily compounds that act as solvents for the nonpolar capsaicin.8 Application of ice water or a high-potency topical steroid also may help. If the reaction is severe and persistent, a continuous stellate ganglion block may alleviate the pain of capsaicin-induced contact dermatitis.9
Identifying Features and Plant Facts
The Capsicum genus includes chili peppers, paprika, and red peppers. Capsicum peppers are native to tropical regions of the Americas (Figure). The use of Capsicum peppers in food can be traced to Indigenous peoples of Mexico as early as 7000
Capsicum belongs to the family Solanaceae, which includes tobacco, tomatoes, potatoes, and nightshade plants. There are many varieties of peppers in the Capsicum genus, with 5 domesticated species: Capsicum annuum, Capsicum baccatum, Capsicum chinense, Capsicum frutescens, and Capsicum pubescens. These include bell, poblano, cayenne, tabasco, habanero, and ají peppers, among others. Capsicum species grow as a shrub with flowers that rotate to stellate corollas and rounded berries of different sizes and colors.12 Capsaicin and other alkaloids are concentrated in the fruit; therefore, Capsicum dermatitis is most commonly induced by contact with the flesh of peppers.
Irritant Chemicals
Capsaicin (8-methyl-6-nonanoyl vanillylamide) is a nonpolar phenol, which is why washing skin that has come in contact with capsaicin with water or vinegar alone is insufficient to solubilize it.13 Capsaicin binds to the transient receptor potential vanilloid 1 (TRPV1), a calcium channel on neurons that opens in response to heat. When bound, the channel opens at a lower temperature threshold and depolarizes nerve endings, leading to vasodilation and activation of sensory nerves.14 Substance P is released and the individual experiences a painful burning sensation. When purified capsaicin is frequently applied at an appropriate dose, synthesis of substance P is diminished, resulting in reduced local pain overall.15
Capsaicin does not affect neurons without TRPV1, and administration of capsaicin is not painful if given with anesthesia. An inappropriately high dose of capsaicin destroys cells in the epidermal barrier, resulting in water loss and inducing release of vasoactive peptides and inflammatory cytokines.1 Careful handling of Capsicum peppers and capsaicin products can reduce the risk for irritation.
Medicinal Use
On-/Off-Label and Potential Uses—Capsaicin is US Food and Drug Administration approved for use in arthritis and musculoskeletal pain. It also is used to treat diabetic neuropathy,5 postherpetic neuralgia,6 psoriasis,16 and other conditions. Studies have shown that capsaicin might be useful in treating trigeminal neuralgia,17 fibromyalgia,18 migraines,14 cluster headaches,9 and HIV-associated distal sensory neuropathy.5
Delivery of Capsaicin—Capsaicin preferentially acts on C-fibers, which transmit dull, aching, chronic pain.19 The compound is available as a cream, lotion, and large bandage (for the lower back), as well as low- and high-dose patches. Capsaicin creams, lotions, and the low-dose patch are uncomfortable and must be applied for 4 to 6 weeks to take effect, which may impact patient adherence. The high-dose patch, which requires administration under local anesthesia by a health care worker, brings pain relief with a single use and improves adherence.11 Synthetic TRPV1-agonist injectables based on capsaicin have undergone clinical trials for localized pain (eg, postoperative musculoskeletal pain); many patients experience pain relief, though benefit fades over weeks to months.20,21
Use in Traditional Medicine—Capsicum peppers have been used to aid digestion and promote healing in gastrointestinal conditions, such as dyspepsia.22 The peppers are a source of important vitamins and minerals, including vitamins A, C, and E; many of the B complex vitamins; and magnesium, calcium, and iron.23
Use as Cancer Therapy—Studies of the use of capsaicin in treating cancer have produced controversial results. In cell and animal models, capsaicin induces apoptosis through downregulation of the Bcl-2 protein; upregulation of oxidative stress, tribbles-related protein 3 (TRIB3), and caspase-3; and other pathways.19,24-26 On the other hand, consumption of Capsicum peppers has been associated with cancer of the stomach and gallbladder.27 Capsaicin might have anticarcinogenic properties, but its mechanism of action varies, depending on variables not fully understood.
Final Thoughts
Capsaicin is a neuropeptide-active compound found in Capsicum peppers that has many promising applications for use. However, dermatologists should be aware of the possibility of a skin reaction to this compound from handling peppers and using topical medicines. Exposure to capsaicin can cause irritant contact dermatitis that may require clinical care.
- Otang WM, Grierson DS, Afolayan AJ. A survey of plants responsible for causing irritant contact dermatitis in the Amathole district, Eastern Cape, South Africa. J Ethnopharmacol. 2014;157:274-284. doi:10.1016/j.jep.2014.10.002
- Weinberg RB. Hunan hand. N Engl J Med. 1981;305:1020.
- Lambrecht C, Goossens A. Occupational allergic contact dermatitis caused by capsicum. Contact Dermatitis. 2015;72:252-253. doi:10.1111/cod.12345
- Haar RJ, Iacopino V, Ranadive N, et al. Health impacts of chemical irritants used for crowd control: a systematic review of the injuries and deaths caused by tear gas and pepper spray. BMC Public Health. 2017;17:831. doi:10.1186/s12889-017-4814-6
- Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18:42-53. doi:10.1016/j.jpain.2016.09.008
- Yong YL, Tan LT-H, Ming LC, et al. The effectiveness and safety of topical capsaicin in postherpetic neuralgia: a systematic review and meta-analysis. Front Pharmacol. 2016;7:538. doi:10.3389/fphar.2016.00538
- Firoz EF, Levin JM, Hartman RD, et al. Lip plumper contact urticaria. J Am Acad Dermatol. 2009;60:861-863. doi:10.1016/j.jaad.2008.09.028
- Jones LA, Tandberg D, Troutman WG. Household treatment for “chile burns” of the hands. J Toxicol Clin Toxicol. 1987;25:483-491. doi:10.3109/15563658708992651
- Saxena AK, Mandhyan R. Multimodal approach for the management of Hunan hand syndrome: a case report. Pain Pract. 2013;13:227-230. doi:10.1111/j.1533-2500.2012.00567.x
- Cordell GA, Araujo OE. Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother. 1993;27:330-336. doi:10.1177/106002809302700316
- Baranidharan G, Das S, Bhaskar A. A review of the high-concentration capsaicin patch and experience in its use in the management of neuropathic pain. Ther Adv Neurol Disord. 2013;6:287-297. doi:10.1177/1756285613496862
- Carrizo García C, Barfuss MHJ, Sehr EM, et al. Phylogenetic relationships, diversification and expansion of chili peppers (Capsicum, Solanaceae). Ann Bot. 2016;118:35-51. doi:10.1093/aob/mcw079
- Basharat S, Gilani SA, Iftikhar F, et al. Capsaicin: plants of the genus Capsicum and positive effect of Oriental spice on skin health. Skin Pharmacol Physiol. 2020;33:331-341. doi:10.1159/000512196
- Hopps JJ, Dunn WR, Randall MD. Vasorelaxation to capsaicin and its effects on calcium influx in arteries. Eur J Pharmacol. 2012;681:88-93. doi:10.1016/j.ejphar.2012.02.019
- Burks TF, Buck SH, Miller MS. Mechanisms of depletion of substance P by capsaicin. Fed Proc. 1985;44:2531-2534.
- Ellis CN, Berberian B, Sulica VI, et al. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol. 1993;29:438-442. doi:10.1016/0190-9622(93)70208-b
- Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg. 1992;74:375-377. doi:10.1213/00000539-199203000-00011
- Casanueva B, Rodero B, Quintial C, et al. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int. 2013;33:2665-2670. doi:10.1007/s00296-012-2490-5
- Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40:847-873. doi:10.1177/0192623312444471
- Jones IA, Togashi R, Wilson ML, et al. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15:77-90. doi:10.1038/s41584-018-0123-4
- Campbell JN, Stevens R, Hanson P, et al. Injectable capsaicin for the management of pain due to osteoarthritis. Molecules. 2021;26:778.
- Maji AK, Banerji P. Phytochemistry and gastrointestinal benefits of the medicinal spice, Capsicum annum L. (chilli): a review. J Complement Integr Med. 2016;13:97-122. doi:10.1515jcim-2015-0037
- Baenas N, Belovié M, Ilie N, et al. Industrial use of pepper (Capsicum annum L.) derived products: technological benefits and biological advantages. Food Chem. 2019;274:872-885. doi:10.1016/j.foodchem.2018.09.047
- Lin RJ, Wu IJ, Hong JY, et al. Capsaicin-induced TRIB3 upregulation promotes apoptosis in cancer cells. Cancer Manag Res. 2018;10:4237-4248. doi:10.2147/CMAR.S162383
- Jung MY, Kang HJ, Moon A. Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett. 2001;165:139-145. doi:10.1016/s0304-3835(01)00426-8
- Ito K, Nakazato T, Yamato K, et al. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004;64:1071-1078. doi:10.1158/0008-5472.can-03-1670
- Báez S, Tsuchiya Y, Calvo A, et al. Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. World J Gastroenterol. 2010;16:372-378. doi:10.3748/wjg.v16.i3.372
- Otang WM, Grierson DS, Afolayan AJ. A survey of plants responsible for causing irritant contact dermatitis in the Amathole district, Eastern Cape, South Africa. J Ethnopharmacol. 2014;157:274-284. doi:10.1016/j.jep.2014.10.002
- Weinberg RB. Hunan hand. N Engl J Med. 1981;305:1020.
- Lambrecht C, Goossens A. Occupational allergic contact dermatitis caused by capsicum. Contact Dermatitis. 2015;72:252-253. doi:10.1111/cod.12345
- Haar RJ, Iacopino V, Ranadive N, et al. Health impacts of chemical irritants used for crowd control: a systematic review of the injuries and deaths caused by tear gas and pepper spray. BMC Public Health. 2017;17:831. doi:10.1186/s12889-017-4814-6
- Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18:42-53. doi:10.1016/j.jpain.2016.09.008
- Yong YL, Tan LT-H, Ming LC, et al. The effectiveness and safety of topical capsaicin in postherpetic neuralgia: a systematic review and meta-analysis. Front Pharmacol. 2016;7:538. doi:10.3389/fphar.2016.00538
- Firoz EF, Levin JM, Hartman RD, et al. Lip plumper contact urticaria. J Am Acad Dermatol. 2009;60:861-863. doi:10.1016/j.jaad.2008.09.028
- Jones LA, Tandberg D, Troutman WG. Household treatment for “chile burns” of the hands. J Toxicol Clin Toxicol. 1987;25:483-491. doi:10.3109/15563658708992651
- Saxena AK, Mandhyan R. Multimodal approach for the management of Hunan hand syndrome: a case report. Pain Pract. 2013;13:227-230. doi:10.1111/j.1533-2500.2012.00567.x
- Cordell GA, Araujo OE. Capsaicin: identification, nomenclature, and pharmacotherapy. Ann Pharmacother. 1993;27:330-336. doi:10.1177/106002809302700316
- Baranidharan G, Das S, Bhaskar A. A review of the high-concentration capsaicin patch and experience in its use in the management of neuropathic pain. Ther Adv Neurol Disord. 2013;6:287-297. doi:10.1177/1756285613496862
- Carrizo García C, Barfuss MHJ, Sehr EM, et al. Phylogenetic relationships, diversification and expansion of chili peppers (Capsicum, Solanaceae). Ann Bot. 2016;118:35-51. doi:10.1093/aob/mcw079
- Basharat S, Gilani SA, Iftikhar F, et al. Capsaicin: plants of the genus Capsicum and positive effect of Oriental spice on skin health. Skin Pharmacol Physiol. 2020;33:331-341. doi:10.1159/000512196
- Hopps JJ, Dunn WR, Randall MD. Vasorelaxation to capsaicin and its effects on calcium influx in arteries. Eur J Pharmacol. 2012;681:88-93. doi:10.1016/j.ejphar.2012.02.019
- Burks TF, Buck SH, Miller MS. Mechanisms of depletion of substance P by capsaicin. Fed Proc. 1985;44:2531-2534.
- Ellis CN, Berberian B, Sulica VI, et al. A double-blind evaluation of topical capsaicin in pruritic psoriasis. J Am Acad Dermatol. 1993;29:438-442. doi:10.1016/0190-9622(93)70208-b
- Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg. 1992;74:375-377. doi:10.1213/00000539-199203000-00011
- Casanueva B, Rodero B, Quintial C, et al. Short-term efficacy of topical capsaicin therapy in severely affected fibromyalgia patients. Rheumatol Int. 2013;33:2665-2670. doi:10.1007/s00296-012-2490-5
- Bley K, Boorman G, Mohammad B, et al. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40:847-873. doi:10.1177/0192623312444471
- Jones IA, Togashi R, Wilson ML, et al. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15:77-90. doi:10.1038/s41584-018-0123-4
- Campbell JN, Stevens R, Hanson P, et al. Injectable capsaicin for the management of pain due to osteoarthritis. Molecules. 2021;26:778.
- Maji AK, Banerji P. Phytochemistry and gastrointestinal benefits of the medicinal spice, Capsicum annum L. (chilli): a review. J Complement Integr Med. 2016;13:97-122. doi:10.1515jcim-2015-0037
- Baenas N, Belovié M, Ilie N, et al. Industrial use of pepper (Capsicum annum L.) derived products: technological benefits and biological advantages. Food Chem. 2019;274:872-885. doi:10.1016/j.foodchem.2018.09.047
- Lin RJ, Wu IJ, Hong JY, et al. Capsaicin-induced TRIB3 upregulation promotes apoptosis in cancer cells. Cancer Manag Res. 2018;10:4237-4248. doi:10.2147/CMAR.S162383
- Jung MY, Kang HJ, Moon A. Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett. 2001;165:139-145. doi:10.1016/s0304-3835(01)00426-8
- Ito K, Nakazato T, Yamato K, et al. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004;64:1071-1078. doi:10.1158/0008-5472.can-03-1670
- Báez S, Tsuchiya Y, Calvo A, et al. Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women. World J Gastroenterol. 2010;16:372-378. doi:10.3748/wjg.v16.i3.372
Practice Points
- Capsicum peppers—used worldwide in food preparation, pepper spray, and cosmetic products—can cause irritant dermatitis from the active ingredient capsaicin.
- Capsaicin, which is isolated as a medication to treat musculoskeletal pain, postherpetic neuralgia, and more, can cause a mild local skin reaction.
