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This Rash Really Stinks!
ANSWER
The correct diagnosis is Darier disease (choice “d”).
DISCUSSION
Darier disease, also known as Darier-White disease or keratosis follicularis, is an inherited defect transmitted by autosomal dominant mode. The pathophysiologic process is a breakdown of cell adhesion that normally binds keratin filaments to tiny connecting fibers called desmosomes.
Darier disease manifests with a “branny” papulosquamous rash, typically arising in the third decade of life and affecting the chest, scalp, back, and intertriginous areas. The nail and intraoral findings noted in this patient are typical. In the author’s experience, the former is more commonly seen and is essentially pathognomic for the disease.
Darier disease is relatively rare, occurring in 1:30,000 to 1:100,000 population, depending on the geographic area studied. Men and women are equally affected, although it is more common in those with darker skin.
The differential outlined in the answer choices is reasonable, considering the condition’s rarity and how unlikely it is to manifest solely in the inframammary area. One could conclude that, just as with psoriasis (choice “b”) and seborrhea, intertrigo (choice “c”) is not always a primary process. And although yeast infection (choice “a”) can complicate any florid rash in this area, topical and oral anti-yeast treatment had utterly failed to help.
TREATMENT
Isotretinoin is used in cases such as this one, but it only offers temporary relief. For less severe cases, oral antibiotics (eg minocycline) or topical steroids (used with caution given the risk for atrophy in the inframammary area) often suffice. This patient’s prognosis is guarded at best, although control of the worst is certainly possible.
ANSWER
The correct diagnosis is Darier disease (choice “d”).
DISCUSSION
Darier disease, also known as Darier-White disease or keratosis follicularis, is an inherited defect transmitted by autosomal dominant mode. The pathophysiologic process is a breakdown of cell adhesion that normally binds keratin filaments to tiny connecting fibers called desmosomes.
Darier disease manifests with a “branny” papulosquamous rash, typically arising in the third decade of life and affecting the chest, scalp, back, and intertriginous areas. The nail and intraoral findings noted in this patient are typical. In the author’s experience, the former is more commonly seen and is essentially pathognomic for the disease.
Darier disease is relatively rare, occurring in 1:30,000 to 1:100,000 population, depending on the geographic area studied. Men and women are equally affected, although it is more common in those with darker skin.
The differential outlined in the answer choices is reasonable, considering the condition’s rarity and how unlikely it is to manifest solely in the inframammary area. One could conclude that, just as with psoriasis (choice “b”) and seborrhea, intertrigo (choice “c”) is not always a primary process. And although yeast infection (choice “a”) can complicate any florid rash in this area, topical and oral anti-yeast treatment had utterly failed to help.
TREATMENT
Isotretinoin is used in cases such as this one, but it only offers temporary relief. For less severe cases, oral antibiotics (eg minocycline) or topical steroids (used with caution given the risk for atrophy in the inframammary area) often suffice. This patient’s prognosis is guarded at best, although control of the worst is certainly possible.
ANSWER
The correct diagnosis is Darier disease (choice “d”).
DISCUSSION
Darier disease, also known as Darier-White disease or keratosis follicularis, is an inherited defect transmitted by autosomal dominant mode. The pathophysiologic process is a breakdown of cell adhesion that normally binds keratin filaments to tiny connecting fibers called desmosomes.
Darier disease manifests with a “branny” papulosquamous rash, typically arising in the third decade of life and affecting the chest, scalp, back, and intertriginous areas. The nail and intraoral findings noted in this patient are typical. In the author’s experience, the former is more commonly seen and is essentially pathognomic for the disease.
Darier disease is relatively rare, occurring in 1:30,000 to 1:100,000 population, depending on the geographic area studied. Men and women are equally affected, although it is more common in those with darker skin.
The differential outlined in the answer choices is reasonable, considering the condition’s rarity and how unlikely it is to manifest solely in the inframammary area. One could conclude that, just as with psoriasis (choice “b”) and seborrhea, intertrigo (choice “c”) is not always a primary process. And although yeast infection (choice “a”) can complicate any florid rash in this area, topical and oral anti-yeast treatment had utterly failed to help.
TREATMENT
Isotretinoin is used in cases such as this one, but it only offers temporary relief. For less severe cases, oral antibiotics (eg minocycline) or topical steroids (used with caution given the risk for atrophy in the inframammary area) often suffice. This patient’s prognosis is guarded at best, although control of the worst is certainly possible.
A 50-year-old woman is referred to dermatology with a “yeast” infection of several years’ duration. The condition causes considerable discomfort, especially during hot weather when the rash emits a very objectionable odor.
The florid, white, scaly rash under her breasts is a stark contrast to the patient’s type V skin. On both sides, the affected skin perfectly matches the inframammary fold. There are sharp margins and uniform moist scaling.
Looking elsewhere, 7 of 10 fingernails exhibit longitudinal white and red streaks, along with triangular nicks in the edges of several nails. The roof of the patient’s mouth is studded with fleshy nodules measuring 0.6 to 1.0 cm. Several pits are seen on her palms.
The patient is in no distress but is quite agitated by the lack of effective treatment. She reports trying a number of prescription and OTC anti-yeast creams, lotions, and oral medications, none of which resolved the problem.
History-taking reveals a family history of skin problems, although neither the patient nor anyone else in the family has ever been seen by a dermatologist. No one has ever suggested that a biopsy be done.
A punch biopsy is performed on the affected inframammary skin. The pathology report shows acantholysis with focal dyskeratotic keratinocytes. Intraepidermal separation is seen throughout the specimen.
Is pediatric subspecialty training financially worth it?
Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.
Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.
“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.
The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
Pediatric subspecialty training rarely pays off
However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”
Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.
For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.
They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.
Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
The financial gap has worsened
To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.
The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.
The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.
“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.
Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.
The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
‘Pediatric subspecialty training is worth it!’
Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.
“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”
But it’s also important for trainees to be aware of economic considerations in their decision-making.
Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.
“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”
A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.
The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.
The authors and Dr. Mink have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.
Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.
“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.
The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
Pediatric subspecialty training rarely pays off
However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”
Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.
For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.
They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.
Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
The financial gap has worsened
To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.
The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.
The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.
“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.
Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.
The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
‘Pediatric subspecialty training is worth it!’
Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.
“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”
But it’s also important for trainees to be aware of economic considerations in their decision-making.
Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.
“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”
A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.
The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.
The authors and Dr. Mink have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Pursuing fellowship training is often financially costly in terms of lifetime earnings, compared with starting a career as a general pediatrician immediately after residency, a report suggests.
Researchers found that most pediatric subspecialists – including those practicing neurology, pulmonology, and adolescent medicine – do not see a financial return from additional training because of the delays in receiving increased compensation and the repayment of educational debt.
“Most pediatric subspecialists don’t experience a relative increase in compensation after training compared to a general pediatrician, so there isn’t a financial benefit to additional training,” lead author Eva Catenaccio, MD, from the division of pediatric neurology, department of neurology, Johns Hopkins University, Baltimore, told this news organization.
The findings, published online March 8 in Pediatrics, contribute to the ongoing debate about the length of pediatric fellowship training programs. The data also provide evidence for the potential effect of a pediatric subspecialty loan repayment program.
Pediatric subspecialty training rarely pays off
However, not all practitioners in pediatric subspecialties would find themselves in the red relative to their generalist peers. Three subspecialties had a positive financial return: cardiology, critical care, and neonatology. Dr. Catenaccio explained that this may be because these subspecialties tend to be “inpatient procedure oriented, which are often more [lucrative] than outpatient cognitive–oriented subspecialties, such as pediatric infectious diseases, endocrinology, or adolescent medicine.”
Enrolling in a pediatric fellowship program resulted in lifetime financial returns that ranged from an increase of $852,129 for cardiology, relative to general pediatrics, to a loss of $1,594,366 for adolescent medicine, researchers found.
For the study, researchers calculated the financial returns of 15 pediatric subspecialties – emergency medicine, neurology, cardiology, critical care, neonatology, hematology and oncology, pulmonology, hospitalist medicine, allergy and immunology, gastroenterology, rheumatology, nephrology, adolescent medicine, infectious diseases, and endocrinology – in comparison with returns of private practice general pediatrics on the basis of 2018-2019 data on fellowship stipends, compensation, and educational debt.
They obtained most of the data from the Association of American Medical Colleges Survey of Resident/Fellow Stipends and Benefits, AAMC’s annual Medical School Faculty Salary Report, and the AAMC Medical School Graduation Questionnaire.
Richard Mink, MD, department of pediatrics, Harbor-UCLA Medical Center, Torrance, Calif., noted that it would have been helpful to have also compared the lifetime earnings of practitioners in pediatric subspecialties to academic general pediatricians and not just those in private practice.
The financial gap has worsened
To better understand which aspects of fellowship training have the greatest effect on lifetime compensation, Dr. Catenaccio and colleagues evaluated the potential effects of shortening fellowship length, eliminating school debt, and implementing a federal loan repayment plan. These changes enhanced the returns of cardiology, critical care, and neonatology – subspecialties that had already seen financial returns before these changes – and resulted in a positive financial return for emergency medicine.
The changes also narrowed the financial gap between subspecialties and general pediatrics. However, the remaining subspecialties still earned less than private practice pediatrics.
The new study is an update to a 2011 report, which reflected 2007-2008 data for 11 subspecialties. This time around, the researchers included the subspecialty of hospitalist medicine, which was approved as a board-certified subspecialty by the American Board of Pediatrics in 2014, as well as neurology, allergy and immunology, and adolescent medicine.
“I was most surprised that the additional pediatric subspecialties we included since the 2011 report followed the same general trend, with pediatric subspecialty training having a lower lifetime earning potential than general pediatrics,” Dr. Catenaccio said.
Comparing results from the two study periods showed that the financial gap between general pediatrics and subspecialty pediatrics worsened over time. For example, the financial return for pediatric endocrinology decreased an additional $500,000 between 2007 and 2018.
The researchers believe a combination of increased educational debt burden, slow growth in compensation, and changing interest rates over time have caused the financial differences between general pediatrics and subspecialty pediatrics to become more pronounced.
‘Pediatric subspecialty training is worth it!’
Despite the financial gaps, Dr. Catenaccio and colleagues say pediatric subspecialty training is still worthwhile but that policymakers should address these financial differences to help guide workforce distribution in a way that meets the needs of patients.
“I think pediatric subspecialty training is worth it,” said Dr. Catenaccio, who’s pursuing pediatric subspecialty training. “There are so many factors that go into choosing a specialty or subspecialty in medicine, including the desire to care for a particular patient population, interest in certain diseases or organ systems, lifestyle considerations, and research opportunities.”
But it’s also important for trainees to be aware of economic considerations in their decision-making.
Dr. Mink, who wrote an accompanying commentary, agrees that young clinicians should not make career decisions on the basis of metrics such as lifetime earning measures.
“I think people who go into pediatrics have decided that money is not the driving force,” said Dr. Mink. He noted that pediatricians are usually not paid well, compared with other specialists. “To me the important thing is you have to like what you’re doing.”
A 2020 study found that trainees who chose a career in pediatric pulmonology, a subspecialty, said that financial considerations were not the driving factor in their decision-making. Nevertheless, Dr. Mink also believes young clinicians should take into account their educational debt.
The further widening of the financial gap between general pediatrics and pediatric subspecialties could lead to shortages in the pediatric subspecialty workforce.
The authors and Dr. Mink have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sun exposure linked to reduced pediatric MS risk
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, research shows. The use of sunscreen does not appear to affect the risk.
“This is the first study, as far as we are aware, to investigate the effect of sun exposure in pediatric MS,” first author Prince Sebastian, of the ANU Medical School, Australian National University, Canberra, said during a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
“In order to reduce the incidence of MS, parents should be encouraged to allow their children to spend at least 30 minutes outdoors in the sun every day, while using adequate sun protection,” Mr. Sebastian said.
“This is especially important for children with a family history of MS,” he said. As the findings show, “you can use adequate sun protection and still get the benefit of sun exposure in terms of MS risk reduction.”
Low sun exposure, exposure to ultraviolet light, and vitamin D have been well established as modifiable risk factors for MS in adults. However, research is lacking on the effect of these factors upon patients younger than 18 years who have pediatric MS, a less common form of the disease. Pediatric MS constitutes about 5% of all MS cases.
To investigate the issue, Mr. Sebastian and colleagues evaluated data on 332 patients with pediatric MS who were between the ages of 4 and 22 years. The patients were enrolled at 16 MS centers around the United States. They were compared by sex and age with 534 control persons aged 3-22 years who did not have MS.
For the patients with MS, the median disease duration was 7.3 months, and 63% were female. The median age of the patients was 15.9 years.
Compared with those who did not have MS, patients with MS were significantly less likely to have been exposed to cigarette smoke (17.8% vs. 14.2%). They were significantly more likely to be overweight (23.8% vs. 14.2%), and the median anti-VCA level was higher (3.7 vs. 2.2).
Those who were exposed to the sun during the most recent summer for a duration of 30 minutes to 1 hour daily, as determined on the basis of self-report or parent report, had a 2.6-fold reduced risk of having MS, compared with those who spent less than 30 minutes outdoors daily (odds ratio, 0.39; P < .05), after adjusting for age, sex, birth season, the child’s skin color, the mother’s education, smoke exposure, being overweight, and Epstein-Barr virus infection.
Sun exposure for 1-2 hours daily was associated with a 7.4-fold reduced risk for MS, compared with exposure of 30 minutes or less (OR, 0.13; P < .001).
The odds were similar for those with 2-3 hours of sun exposure (OR, 0.21; P < .001) and for those with more than 3 hours of daily exposure (OR, 0.14; P < .001), versus less than 30 minutes.
Mr. Sebastian and his team also assessed the role of summer ambient levels of UV light and whether such exposure conferred a similar degree of protection. The risk for MS was lower among those who were exposed to higher summer ambient UV levels than among those exposed to lower levels (OR, 0.80; P = .046).
He noted, “Based on the results, individuals residing in Florida (28° N) would have 20% lower odds of MS, compared with an individual residing in New York (40° N).”
Interestingly, median rates of the use of sun protection were similar for the participants with MS and those without MS (OR, 0.95), suggesting that the use of sunscreen did not reduce the protective effect of sun exposure.
“We predicted that greater use of protection would limit effective sun exposure and would therefore increase MS risk,” Mr. Sebastian said, “but we don’t see that, and it’s probably because someone who uses sun protection likely gets more sun exposure anyway.”
“Our results suggest that you can use adequate sun protection and still get most of the benefit in terms of MS prevention, which is quite encouraging,” he added.
For those with MS, median serum 25(OH)D levels were higher (27.7 ng/mL vs. 23.7 ng/mL; P < .001), but Mr. Sebastian noted that this difference was likely attributable to the use of vitamin D supplementation after an MS diagnosis. An important limitation of the study was a lack of data on supplementation.
Stronger effect of frequent sun protection
Previous studies have shown a link between sun exposure and MS. A study published in 2018 compared 2,251 patients with MS with 4,028 control persons who did not have MS. The participants were in Canada, Italy, and Norway.
In that study, for most of the patients with MS, the age of onset was older than 18 years. In that study, there was a nearly 50% increased risk among those with the lowest degree of summer sun exposure in comparison with those who had the highest level of exposure (risk ratio, 1.47).
Contrary to the current study, that study did show an effect of the use of sun protection – those with the lowest degree of sun exposure during summer and winter and the highest use of sun protection had the highest risk for MS. They had a 76% increased risk, compared with those who had the highest degree of sun exposure and the least use of sun protection (RR, 1.76).
Sandra Magalhaes, PhD, of the University of New Brunswick, Fredericton, Canada, who was first author on that study, noted that the new study of pediatric MS adds valuable evidence on the issue.
“This study is important, as it adds to the etiological literature on MS implicating relevance of sun exposure,” Dr. Magalhaes said.
“We have a number of studies that have demonstrated an important effect of reduced levels of sun exposure and increased risk of MS. However, these studies focus on adult-onset MS populations; rather, the new study adds to the existing literature, as it also implicates sun exposure in etiology of pediatric-onset MS,” she said.
Notably, their previous work, unlike the current study, showed that, among those who experienced low levels of sun exposure, the risk for MS was higher for those who used sunscreen frequently.
“Overall, in their limited time outdoors, use of sunscreen may further increase risk of MS, which makes sense, since limited time outdoors in less sun, adding sun protection means [exposure to] even less sun.”
The findings of both studies support the bulk of research indicating that sun exposure is beneficial with regard to MS.
“There is a need for promoting balanced safe sun practices to reduce disease burden, especially in countries and cultures where children spend a lot of time indoors,” Dr. Magalhaes said. “Sun exposure has a number of important physiological roles, including vitamin D synthesis but also immune system functioning.”
Mr. Sebastian and Dr. Magalhaes have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACTRIMS FORUM 2021
New inhibitor shows promise in previously failed B-cell malignancies
who discontinued prior Bruton’s tyrosine kinase (BTK)–inhibitor treatment due to resistance or intolerance, according to the results of the BRUIN trial, a phase 1/2 study.
Pirtobrutinib (formerly known as LOXO-305) is an oral-dose, highly selective, reversible BTK inhibitor, which might address a growing, unmet need for alternative therapies in BTK-inhibitor treatment failure patients, according to Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Their report was published in The Lancet.
The study included 109 women (34%) and 214 men (66%), with a median age of 68 years, who were treated with pirtobrutinib. Of these, 203 patients were assigned to pirtobrutinib (25-300 mg once per day) in the phase 1 portion of the study, and 120 patients were assigned to pirtobrutinib (200 mg once per day) in phase 2.
Promising outcomes
Pirtobrutinib, showed promising efficacy and tolerable safety in patients with CLL or small lymphocytic lymphoma, mantle cell lymphoma, and Waldenström macroglobulinemia who were previously treated with a BTK inhibitor. In 121 efficacy-evaluable patients with CLL or SLL treated with a previous covalent BTK inhibitor, the overall response rate with pirtobrutinib was 62% (95% confidence interval, 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (67%), covalent BTK inhibitor intolerance (52%), BTK C481-mutant (71%), and BTK wild-type (66%) disease.
In 52 efficacy-evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI, 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but 8 remain progression free to date, the authors stated.
In 19 efficacy-evaluable patients with Waldenström macroglobulinemia, the ORR was 68%. Among eight patients with follicular lymphoma who were efficacy evaluable, responses were observed in four (50%) patients, and six (75%) of eight efficacy evaluable patients with Richter’s transformation identified before enrollment responded to treatment, the authors stated.
No dose-limiting toxicities were observed and the maximum tolerated dose was not reached, according to the researchers. The recommended phase 2 dose was 200 mg daily. The adverse events, which occurred in at least 10% of 323 patients, were fatigue (20%), diarrhea (17%), and contusion (13%). The most common grade 3 or higher adverse event was neutropenia (10%). Five patients (1%) discontinued treatment because of a treatment-related adverse event.
In this “first-in-human trial of pirtobrutinib, we showed promising efficacy and safety in patients with B-cell malignancies, including CLL or SLL, MCL, Waldenström macroglobulinemia, and follicular lymphoma. Activity was observed in heavily pretreated patients, including patients with resistance and intolerance to previous covalent BTK inhibitor treatment. Global randomized phase 3 studies in CLL or SLL, and MCL are planned,” the researchers concluded.
Birth of a third generation?
“The pirtobrutinib study, by opening the way for a third generation of BTK inhibitors, could improve such a personalized molecular approach in the treatment of B-cell malignancies,” according to accompanying editorial comment by Jean-Marie Michot, MD, and Vincent Ribrag, MD, both of the Institut de Cancérologie Gustave Roussy, Villejuif, France.
They discussed how BTK inhibitors have been a considerable therapeutic advance in the treatment of NHL-B and CLL and how the three currently approved BTK inhibitors, namely ibrutinib, acalabrutinib, and zanubrutinib, are all covalent and irreversible inhibitors at the protein – the C481 binding site. “Ibrutinib was the first approved drug. The second-generation inhibitors, acalabrutinib and zanubrutinib, were designed to be more BTK selective,” they added. However, the covalency and irreversibility of the drugs, considered therapeutic strengths, have resulted in induced resistance mutations occurring at the covalent binding, rendering the drugs inactive. “Two advantages of this new drug class are highlighted. First, the selectivity of the drug on BTK appears to be increased,” they wrote. “Second, this class does not bind BTK to the C481 residue, and the efficacy of the drug is therefore not affected by mutations in the BTK binding site.”
Several of the study authors reported receiving grants and personal fees from Loxo Oncology (a wholly owned subsidiary of Eli Lilly), which sponsored the study, as well as financial relationships with other pharmaceutical and biotechnology companies.
Dr. Michot and Dr. Ribrag reported that they had no disclosures relevant to the discussion.
who discontinued prior Bruton’s tyrosine kinase (BTK)–inhibitor treatment due to resistance or intolerance, according to the results of the BRUIN trial, a phase 1/2 study.
Pirtobrutinib (formerly known as LOXO-305) is an oral-dose, highly selective, reversible BTK inhibitor, which might address a growing, unmet need for alternative therapies in BTK-inhibitor treatment failure patients, according to Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Their report was published in The Lancet.
The study included 109 women (34%) and 214 men (66%), with a median age of 68 years, who were treated with pirtobrutinib. Of these, 203 patients were assigned to pirtobrutinib (25-300 mg once per day) in the phase 1 portion of the study, and 120 patients were assigned to pirtobrutinib (200 mg once per day) in phase 2.
Promising outcomes
Pirtobrutinib, showed promising efficacy and tolerable safety in patients with CLL or small lymphocytic lymphoma, mantle cell lymphoma, and Waldenström macroglobulinemia who were previously treated with a BTK inhibitor. In 121 efficacy-evaluable patients with CLL or SLL treated with a previous covalent BTK inhibitor, the overall response rate with pirtobrutinib was 62% (95% confidence interval, 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (67%), covalent BTK inhibitor intolerance (52%), BTK C481-mutant (71%), and BTK wild-type (66%) disease.
In 52 efficacy-evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI, 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but 8 remain progression free to date, the authors stated.
In 19 efficacy-evaluable patients with Waldenström macroglobulinemia, the ORR was 68%. Among eight patients with follicular lymphoma who were efficacy evaluable, responses were observed in four (50%) patients, and six (75%) of eight efficacy evaluable patients with Richter’s transformation identified before enrollment responded to treatment, the authors stated.
No dose-limiting toxicities were observed and the maximum tolerated dose was not reached, according to the researchers. The recommended phase 2 dose was 200 mg daily. The adverse events, which occurred in at least 10% of 323 patients, were fatigue (20%), diarrhea (17%), and contusion (13%). The most common grade 3 or higher adverse event was neutropenia (10%). Five patients (1%) discontinued treatment because of a treatment-related adverse event.
In this “first-in-human trial of pirtobrutinib, we showed promising efficacy and safety in patients with B-cell malignancies, including CLL or SLL, MCL, Waldenström macroglobulinemia, and follicular lymphoma. Activity was observed in heavily pretreated patients, including patients with resistance and intolerance to previous covalent BTK inhibitor treatment. Global randomized phase 3 studies in CLL or SLL, and MCL are planned,” the researchers concluded.
Birth of a third generation?
“The pirtobrutinib study, by opening the way for a third generation of BTK inhibitors, could improve such a personalized molecular approach in the treatment of B-cell malignancies,” according to accompanying editorial comment by Jean-Marie Michot, MD, and Vincent Ribrag, MD, both of the Institut de Cancérologie Gustave Roussy, Villejuif, France.
They discussed how BTK inhibitors have been a considerable therapeutic advance in the treatment of NHL-B and CLL and how the three currently approved BTK inhibitors, namely ibrutinib, acalabrutinib, and zanubrutinib, are all covalent and irreversible inhibitors at the protein – the C481 binding site. “Ibrutinib was the first approved drug. The second-generation inhibitors, acalabrutinib and zanubrutinib, were designed to be more BTK selective,” they added. However, the covalency and irreversibility of the drugs, considered therapeutic strengths, have resulted in induced resistance mutations occurring at the covalent binding, rendering the drugs inactive. “Two advantages of this new drug class are highlighted. First, the selectivity of the drug on BTK appears to be increased,” they wrote. “Second, this class does not bind BTK to the C481 residue, and the efficacy of the drug is therefore not affected by mutations in the BTK binding site.”
Several of the study authors reported receiving grants and personal fees from Loxo Oncology (a wholly owned subsidiary of Eli Lilly), which sponsored the study, as well as financial relationships with other pharmaceutical and biotechnology companies.
Dr. Michot and Dr. Ribrag reported that they had no disclosures relevant to the discussion.
who discontinued prior Bruton’s tyrosine kinase (BTK)–inhibitor treatment due to resistance or intolerance, according to the results of the BRUIN trial, a phase 1/2 study.
Pirtobrutinib (formerly known as LOXO-305) is an oral-dose, highly selective, reversible BTK inhibitor, which might address a growing, unmet need for alternative therapies in BTK-inhibitor treatment failure patients, according to Anthony R. Mato, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. Their report was published in The Lancet.
The study included 109 women (34%) and 214 men (66%), with a median age of 68 years, who were treated with pirtobrutinib. Of these, 203 patients were assigned to pirtobrutinib (25-300 mg once per day) in the phase 1 portion of the study, and 120 patients were assigned to pirtobrutinib (200 mg once per day) in phase 2.
Promising outcomes
Pirtobrutinib, showed promising efficacy and tolerable safety in patients with CLL or small lymphocytic lymphoma, mantle cell lymphoma, and Waldenström macroglobulinemia who were previously treated with a BTK inhibitor. In 121 efficacy-evaluable patients with CLL or SLL treated with a previous covalent BTK inhibitor, the overall response rate with pirtobrutinib was 62% (95% confidence interval, 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (67%), covalent BTK inhibitor intolerance (52%), BTK C481-mutant (71%), and BTK wild-type (66%) disease.
In 52 efficacy-evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI, 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but 8 remain progression free to date, the authors stated.
In 19 efficacy-evaluable patients with Waldenström macroglobulinemia, the ORR was 68%. Among eight patients with follicular lymphoma who were efficacy evaluable, responses were observed in four (50%) patients, and six (75%) of eight efficacy evaluable patients with Richter’s transformation identified before enrollment responded to treatment, the authors stated.
No dose-limiting toxicities were observed and the maximum tolerated dose was not reached, according to the researchers. The recommended phase 2 dose was 200 mg daily. The adverse events, which occurred in at least 10% of 323 patients, were fatigue (20%), diarrhea (17%), and contusion (13%). The most common grade 3 or higher adverse event was neutropenia (10%). Five patients (1%) discontinued treatment because of a treatment-related adverse event.
In this “first-in-human trial of pirtobrutinib, we showed promising efficacy and safety in patients with B-cell malignancies, including CLL or SLL, MCL, Waldenström macroglobulinemia, and follicular lymphoma. Activity was observed in heavily pretreated patients, including patients with resistance and intolerance to previous covalent BTK inhibitor treatment. Global randomized phase 3 studies in CLL or SLL, and MCL are planned,” the researchers concluded.
Birth of a third generation?
“The pirtobrutinib study, by opening the way for a third generation of BTK inhibitors, could improve such a personalized molecular approach in the treatment of B-cell malignancies,” according to accompanying editorial comment by Jean-Marie Michot, MD, and Vincent Ribrag, MD, both of the Institut de Cancérologie Gustave Roussy, Villejuif, France.
They discussed how BTK inhibitors have been a considerable therapeutic advance in the treatment of NHL-B and CLL and how the three currently approved BTK inhibitors, namely ibrutinib, acalabrutinib, and zanubrutinib, are all covalent and irreversible inhibitors at the protein – the C481 binding site. “Ibrutinib was the first approved drug. The second-generation inhibitors, acalabrutinib and zanubrutinib, were designed to be more BTK selective,” they added. However, the covalency and irreversibility of the drugs, considered therapeutic strengths, have resulted in induced resistance mutations occurring at the covalent binding, rendering the drugs inactive. “Two advantages of this new drug class are highlighted. First, the selectivity of the drug on BTK appears to be increased,” they wrote. “Second, this class does not bind BTK to the C481 residue, and the efficacy of the drug is therefore not affected by mutations in the BTK binding site.”
Several of the study authors reported receiving grants and personal fees from Loxo Oncology (a wholly owned subsidiary of Eli Lilly), which sponsored the study, as well as financial relationships with other pharmaceutical and biotechnology companies.
Dr. Michot and Dr. Ribrag reported that they had no disclosures relevant to the discussion.
FROM THE LANCET
Have you used ambulatory cervical ripening in your practice?
[polldaddy:10771173]
[polldaddy:10771173]
[polldaddy:10771173]
Meghan Markle interview resurfaces suicidality screening debate
An eye-opening moment during March 7’s Meghan Markle/Prince Harry interview with Oprah Winfrey was Markle’s admission that, before the royal couple moved from the U.K., she was suicidal and had nowhere to turn for help.
For health care practitioners, this has resurfaced the debate over universal suicidality screening and discussion about what should happen when patients screen positive.
The American Psychiatric Association reports suicide is the 10th leading cause of death in the United States, but the second leading cause of death in people age 10-34 years old.
The latest data from the Centers for Disease Control and Prevention show that, in 2019, suicide rates dropped for the first time in 14 years. However, it is widely expected that, in the face of the COVID-19 pandemic and its associated isolation, loneliness, and stress, the next round of data will show a surge in suicide deaths.
, chair of the APA’s Committee on Women’s Mental Health.
“I can see it in my office. People who didn’t necessarily complain about anxiety and depression before or who had been stable for many years are decompensating now,” Dr. De Faria said in an interview.
Although other parts of the interview may have been controversial, said Dr. De Faria, Markle’s disclosure has opened up a much-needed discussion.
“I’m all for people talking about mental health, and I commend [Markle] for sharing her struggle and putting it out there,” she added.
In a perfect world, she noted, there would be universal suicide screening by all medical professionals.
However, Dr. De Faria, associate clinical professor of psychiatry, University of Florida, Gainesville, acknowledged that from a resource standpoint this is not a pragmatic solution.
Primary care physicians are often the frontline defense for suicide prevention, noted Mona Masood, DO, a Philadelphia-area psychiatrist and founder and chief organizer of the Physician Support Line, a free mental health hotline exclusively for doctors staffed by volunteer psychiatrists.
“I believe our general practitioner colleagues, our family medicine colleagues are the ones who are going to be seeing the majority of mental health concerns or illnesses because of the stigma that is often there from seeing a psychiatrist,” Dr. Masood said in an interview.
Dr. De Faria noted that the Patient Health Questionnaire-2 (PHQ-2) for mental health offers a simple screen that includes two key questions. It asks: Over the last 2 weeks, how often have you been bothered by the following problems?
- Little interest or pleasure in doing things.
- Feeling down, depressed, or hopeless.
However, both Dr. De Faria and Dr. Masood emphasized that individualized follow-up questions and follow-up care are equally important.
Unlike Dr. De Faria, who prefers universal screening but understands the challenges of implementing it, Dr. Masood favors targeted screening.
“For physicians, the whole point of what we do is to save lives. To talk to somebody about the complete opposite and to ask, ‘Are you planning on ending your life?’ is very jarring. But for the patient, that may be their only outlet. A primary care provider may be the only professional that they talk to about their mental health,” said Dr. Masood.
Patients can easily say “no” to suicidal ideation questions from a general screen, but targeted, probing questions let patients know that they’re being heard and seen beyond their physical examination, she added.
She also suggested that clinicians ask open-ended questions of those patients who are struggling.
Dr. Masood noted that having a plan in place before screening a patient is especially key.
“I’d argue that one of the subconscious reasons why so many doctors do not ask the question [about suicidality] is because if you ask it, you have to be ready for the answer and to know what you’d do,” she said.
All primary care physicians should have “mental health professionals as resources in your back pocket” in order to have a referral ready to give to patients in need, she said.
“Outside of your clinic time, have a rapport with your local psychiatrist or therapist and know where to send someone who is suicidal,” Dr. Masood said. “Know what is in your local area so you’ll already know how to implement your plan.”
Dr. Masood also recommended:
- Informing staff about protocols for patients with suicidal thoughts who need to go to the hospital for evaluation.
- Creating a safe space in the clinic/office, such as an unused exam room, where patients can wait for next steps.
- Having staff inform a patient’s emergency contact about the situation.
- Trying for a “warm handoff,” where the emergency contact takes the patient to the nearest crisis center and having staff call ahead to let them know to expect the patient.
- If the patient has no emergency contact, following your state’s involuntary crisis response protocol, which involves calling 911 for emergency services.
In addition, the APA’s suicide prevention page includes a long list of helpful resources for patients, families, and physicians.
A version of this article first appeared on Medscape.com.
An eye-opening moment during March 7’s Meghan Markle/Prince Harry interview with Oprah Winfrey was Markle’s admission that, before the royal couple moved from the U.K., she was suicidal and had nowhere to turn for help.
For health care practitioners, this has resurfaced the debate over universal suicidality screening and discussion about what should happen when patients screen positive.
The American Psychiatric Association reports suicide is the 10th leading cause of death in the United States, but the second leading cause of death in people age 10-34 years old.
The latest data from the Centers for Disease Control and Prevention show that, in 2019, suicide rates dropped for the first time in 14 years. However, it is widely expected that, in the face of the COVID-19 pandemic and its associated isolation, loneliness, and stress, the next round of data will show a surge in suicide deaths.
, chair of the APA’s Committee on Women’s Mental Health.
“I can see it in my office. People who didn’t necessarily complain about anxiety and depression before or who had been stable for many years are decompensating now,” Dr. De Faria said in an interview.
Although other parts of the interview may have been controversial, said Dr. De Faria, Markle’s disclosure has opened up a much-needed discussion.
“I’m all for people talking about mental health, and I commend [Markle] for sharing her struggle and putting it out there,” she added.
In a perfect world, she noted, there would be universal suicide screening by all medical professionals.
However, Dr. De Faria, associate clinical professor of psychiatry, University of Florida, Gainesville, acknowledged that from a resource standpoint this is not a pragmatic solution.
Primary care physicians are often the frontline defense for suicide prevention, noted Mona Masood, DO, a Philadelphia-area psychiatrist and founder and chief organizer of the Physician Support Line, a free mental health hotline exclusively for doctors staffed by volunteer psychiatrists.
“I believe our general practitioner colleagues, our family medicine colleagues are the ones who are going to be seeing the majority of mental health concerns or illnesses because of the stigma that is often there from seeing a psychiatrist,” Dr. Masood said in an interview.
Dr. De Faria noted that the Patient Health Questionnaire-2 (PHQ-2) for mental health offers a simple screen that includes two key questions. It asks: Over the last 2 weeks, how often have you been bothered by the following problems?
- Little interest or pleasure in doing things.
- Feeling down, depressed, or hopeless.
However, both Dr. De Faria and Dr. Masood emphasized that individualized follow-up questions and follow-up care are equally important.
Unlike Dr. De Faria, who prefers universal screening but understands the challenges of implementing it, Dr. Masood favors targeted screening.
“For physicians, the whole point of what we do is to save lives. To talk to somebody about the complete opposite and to ask, ‘Are you planning on ending your life?’ is very jarring. But for the patient, that may be their only outlet. A primary care provider may be the only professional that they talk to about their mental health,” said Dr. Masood.
Patients can easily say “no” to suicidal ideation questions from a general screen, but targeted, probing questions let patients know that they’re being heard and seen beyond their physical examination, she added.
She also suggested that clinicians ask open-ended questions of those patients who are struggling.
Dr. Masood noted that having a plan in place before screening a patient is especially key.
“I’d argue that one of the subconscious reasons why so many doctors do not ask the question [about suicidality] is because if you ask it, you have to be ready for the answer and to know what you’d do,” she said.
All primary care physicians should have “mental health professionals as resources in your back pocket” in order to have a referral ready to give to patients in need, she said.
“Outside of your clinic time, have a rapport with your local psychiatrist or therapist and know where to send someone who is suicidal,” Dr. Masood said. “Know what is in your local area so you’ll already know how to implement your plan.”
Dr. Masood also recommended:
- Informing staff about protocols for patients with suicidal thoughts who need to go to the hospital for evaluation.
- Creating a safe space in the clinic/office, such as an unused exam room, where patients can wait for next steps.
- Having staff inform a patient’s emergency contact about the situation.
- Trying for a “warm handoff,” where the emergency contact takes the patient to the nearest crisis center and having staff call ahead to let them know to expect the patient.
- If the patient has no emergency contact, following your state’s involuntary crisis response protocol, which involves calling 911 for emergency services.
In addition, the APA’s suicide prevention page includes a long list of helpful resources for patients, families, and physicians.
A version of this article first appeared on Medscape.com.
An eye-opening moment during March 7’s Meghan Markle/Prince Harry interview with Oprah Winfrey was Markle’s admission that, before the royal couple moved from the U.K., she was suicidal and had nowhere to turn for help.
For health care practitioners, this has resurfaced the debate over universal suicidality screening and discussion about what should happen when patients screen positive.
The American Psychiatric Association reports suicide is the 10th leading cause of death in the United States, but the second leading cause of death in people age 10-34 years old.
The latest data from the Centers for Disease Control and Prevention show that, in 2019, suicide rates dropped for the first time in 14 years. However, it is widely expected that, in the face of the COVID-19 pandemic and its associated isolation, loneliness, and stress, the next round of data will show a surge in suicide deaths.
, chair of the APA’s Committee on Women’s Mental Health.
“I can see it in my office. People who didn’t necessarily complain about anxiety and depression before or who had been stable for many years are decompensating now,” Dr. De Faria said in an interview.
Although other parts of the interview may have been controversial, said Dr. De Faria, Markle’s disclosure has opened up a much-needed discussion.
“I’m all for people talking about mental health, and I commend [Markle] for sharing her struggle and putting it out there,” she added.
In a perfect world, she noted, there would be universal suicide screening by all medical professionals.
However, Dr. De Faria, associate clinical professor of psychiatry, University of Florida, Gainesville, acknowledged that from a resource standpoint this is not a pragmatic solution.
Primary care physicians are often the frontline defense for suicide prevention, noted Mona Masood, DO, a Philadelphia-area psychiatrist and founder and chief organizer of the Physician Support Line, a free mental health hotline exclusively for doctors staffed by volunteer psychiatrists.
“I believe our general practitioner colleagues, our family medicine colleagues are the ones who are going to be seeing the majority of mental health concerns or illnesses because of the stigma that is often there from seeing a psychiatrist,” Dr. Masood said in an interview.
Dr. De Faria noted that the Patient Health Questionnaire-2 (PHQ-2) for mental health offers a simple screen that includes two key questions. It asks: Over the last 2 weeks, how often have you been bothered by the following problems?
- Little interest or pleasure in doing things.
- Feeling down, depressed, or hopeless.
However, both Dr. De Faria and Dr. Masood emphasized that individualized follow-up questions and follow-up care are equally important.
Unlike Dr. De Faria, who prefers universal screening but understands the challenges of implementing it, Dr. Masood favors targeted screening.
“For physicians, the whole point of what we do is to save lives. To talk to somebody about the complete opposite and to ask, ‘Are you planning on ending your life?’ is very jarring. But for the patient, that may be their only outlet. A primary care provider may be the only professional that they talk to about their mental health,” said Dr. Masood.
Patients can easily say “no” to suicidal ideation questions from a general screen, but targeted, probing questions let patients know that they’re being heard and seen beyond their physical examination, she added.
She also suggested that clinicians ask open-ended questions of those patients who are struggling.
Dr. Masood noted that having a plan in place before screening a patient is especially key.
“I’d argue that one of the subconscious reasons why so many doctors do not ask the question [about suicidality] is because if you ask it, you have to be ready for the answer and to know what you’d do,” she said.
All primary care physicians should have “mental health professionals as resources in your back pocket” in order to have a referral ready to give to patients in need, she said.
“Outside of your clinic time, have a rapport with your local psychiatrist or therapist and know where to send someone who is suicidal,” Dr. Masood said. “Know what is in your local area so you’ll already know how to implement your plan.”
Dr. Masood also recommended:
- Informing staff about protocols for patients with suicidal thoughts who need to go to the hospital for evaluation.
- Creating a safe space in the clinic/office, such as an unused exam room, where patients can wait for next steps.
- Having staff inform a patient’s emergency contact about the situation.
- Trying for a “warm handoff,” where the emergency contact takes the patient to the nearest crisis center and having staff call ahead to let them know to expect the patient.
- If the patient has no emergency contact, following your state’s involuntary crisis response protocol, which involves calling 911 for emergency services.
In addition, the APA’s suicide prevention page includes a long list of helpful resources for patients, families, and physicians.
A version of this article first appeared on Medscape.com.
Cutaneous allodynia prevalence comparable in patients with migraine and probable migraine
Key clinical point: The prevalence of cutaneous allodynia (CA) was comparable among patients with probable migraine (PM) and migraine. Anxiety, depression, and headache frequency/intensity were significant factors for CA in PM.
Major finding: Participants with PM (n=289) and migraine (n=125) showed a similar prevalence of CA (14.5% vs. 16.0%; P = .701). The factors significantly associated with CA in PM were moderate (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.4) and severe (aOR, 4.0; 95% CI, 1.1-13.9) headache intensity, anxiety (aOR, 5.2; 95% CI, 1.7-16.3), and depression (aOR, 3.3; 95% CI, 1.5-7.6).
Study details: The data come from the Korean Sleep-Headache Study, a population-based, cross-sectional survey on headache and sleep involving 2,501 participants.
Disclosures: This study was supported by the National Research Foundation of Korea grant from the Korean government. S‐J Cho and M K Chu were site investigators for a multicenter trial sponsored by Otsuka Korea, Eli Lilly and Co., and others. S-J Cho and MK Chu have worked as advisory members for Teva and have declared research support/lecture honoraria/grants from different sources. The other authors declared no conflicts of interest.
Source: Han SM et al. Sci Rep. 2021 Jan 28. doi: 10.1038/s41598-021-82080-z.
Key clinical point: The prevalence of cutaneous allodynia (CA) was comparable among patients with probable migraine (PM) and migraine. Anxiety, depression, and headache frequency/intensity were significant factors for CA in PM.
Major finding: Participants with PM (n=289) and migraine (n=125) showed a similar prevalence of CA (14.5% vs. 16.0%; P = .701). The factors significantly associated with CA in PM were moderate (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.4) and severe (aOR, 4.0; 95% CI, 1.1-13.9) headache intensity, anxiety (aOR, 5.2; 95% CI, 1.7-16.3), and depression (aOR, 3.3; 95% CI, 1.5-7.6).
Study details: The data come from the Korean Sleep-Headache Study, a population-based, cross-sectional survey on headache and sleep involving 2,501 participants.
Disclosures: This study was supported by the National Research Foundation of Korea grant from the Korean government. S‐J Cho and M K Chu were site investigators for a multicenter trial sponsored by Otsuka Korea, Eli Lilly and Co., and others. S-J Cho and MK Chu have worked as advisory members for Teva and have declared research support/lecture honoraria/grants from different sources. The other authors declared no conflicts of interest.
Source: Han SM et al. Sci Rep. 2021 Jan 28. doi: 10.1038/s41598-021-82080-z.
Key clinical point: The prevalence of cutaneous allodynia (CA) was comparable among patients with probable migraine (PM) and migraine. Anxiety, depression, and headache frequency/intensity were significant factors for CA in PM.
Major finding: Participants with PM (n=289) and migraine (n=125) showed a similar prevalence of CA (14.5% vs. 16.0%; P = .701). The factors significantly associated with CA in PM were moderate (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.4) and severe (aOR, 4.0; 95% CI, 1.1-13.9) headache intensity, anxiety (aOR, 5.2; 95% CI, 1.7-16.3), and depression (aOR, 3.3; 95% CI, 1.5-7.6).
Study details: The data come from the Korean Sleep-Headache Study, a population-based, cross-sectional survey on headache and sleep involving 2,501 participants.
Disclosures: This study was supported by the National Research Foundation of Korea grant from the Korean government. S‐J Cho and M K Chu were site investigators for a multicenter trial sponsored by Otsuka Korea, Eli Lilly and Co., and others. S-J Cho and MK Chu have worked as advisory members for Teva and have declared research support/lecture honoraria/grants from different sources. The other authors declared no conflicts of interest.
Source: Han SM et al. Sci Rep. 2021 Jan 28. doi: 10.1038/s41598-021-82080-z.
Acute migraine treatment: Real-world data reaffirm efficacy and safety of ubrogepant
Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.
Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.
Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.
Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.
Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.
Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.
Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.
Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.
Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.
Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.
Key clinical point: Survey findings from a real-world tertiary headache clinic support the efficacy and safety of ubrogepant for acute treatment of migraine.
Major finding: Complete headache freedom and headache relief at 2 hours after taking ubrogepant for at least 75% of treated attacks were achieved in 19.0% and 47.6% of patients with migraine, respectively. Overall, 31.1% of patients reported being very satisfied with ubrogepant. Rates of adverse events were higher than those observed in clinical trials. However, no severe/serious adverse events were reported.
Study details: The data come from an analysis of questionnaire responses of 106 adult patients with migraine with or without aura treated with ubrogepant at a tertiary headache center.
Disclosures: No source of funding was declared. DW Dodick declared research support/consulting from various sources. AJ Starling declared consulting fees from Alder, Allergan, Amgen, Axsome Therapeutics, and others. Four of the other authors had no disclosures.
Source: Chiang C-C et al. Headache. 2021 Feb 5. doi: 10.1111/head.14062.
Vasodilatory medications found protective against rosacea
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“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
.
“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
.
“Our initial hypothesis was that perhaps antihypertensive agents might be associated with worsening rosacea,” one of the study authors, Jennifer G. Powers, MD, associate professor of dermatology at the University of Iowa, Iowa City, said in an interview. “What we found was exactly the opposite – that in fact their presence in a medical chart correlated with lower rates of rosacea diagnoses, as defined by ICD 9/10 codes.”
According to the researchers, who published their findings in the Journal of the American Academy of Dermatology, cases of acute vasodilator-induced rosacea have been reported, but no long-term association has been established. “In fact, many widely used antihypertensive medications modulate peripheral vascular tone,” they wrote. “Therefore, chronic use in patients with hypertension may reduce damage to peripheral vessels, and thus decrease risk of rosacea.”
To determine the correlates between vasodilator use and risk of rosacea, Dr. Powers and colleagues identified 680 hypertensive patients being treated with vasodilators or a thiazide diuretic in whom rosacea developed within 5 years of initiating therapy between June 1, 2006, and April 31, 2019. Vasodilator therapies included angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Patients on thiazide diuretics served as the control group. The researchers stratified the patients by age, gender, race, diabetes, chronic kidney disease, and coronary artery disease and calculated relative risk estimates comparing vasodilators with thiazides between strata.
Of the 680 patients, all but 40 were White; 127 were on thiazides, and the remaining 553 were on vasodilators. Overall, the researchers observed that use of vasodilators had a protective effect on the development of rosacea within 5 years, compared with thiazides (relative risk [RR], 0.56; P less than .0001). Specifically, the relative risk was 0.50 for ACE-inhibitors (P less than .0001); 0.69 for ARBs (P = .041); 0.55 for beta-blockers (P less than .0001); and 0.39 for CCBs (P less than .0001).
Dr. Powers and colleagues also observed significant inverse correlations in ACE-inhibitors, beta-blockers, and CCBs among White women aged 50 and older, but no significance was observed in non-White subgroups. The cohorts of patients with chronic kidney disease and coronary artery disease were too small for analysis.
“We were very surprised to find that many of the agents we think of as vasodilators might actually be beneficial for rosacea,” Dr. Powers said. “We would like to see these results reproduced in larger population studies. There are also potential questions about the mechanism at play. However, should these findings hold true, [it’s] all the more reason for our rosacea patients with hypertension to be managed well. They need not fear that those medications are worsening disease. Also, there might be new therapeutic options based on this data.”
The study received funding support from the National Center for Advancing Translational Sciences. The researchers reported having no financial disclosures.
One of Dr. Powers’ coauthors is her husband, Edward M. Powers, MD, a cardiology fellow at the University of Iowa. “We sometimes bounce ideas off one another and will talk about how systemic effects on the vasculature may impact skin disease,” she said, noting that they also published a report on statins and atopic dermatitis.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Dietary magnesium may have a protective role against migraine
Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.
Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).
Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.
Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.
Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).
Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.
Key clinical point: Inadequate magnesium consumption through the diet is associated with migraine in US adults, aged 20-50 years.
Major finding: Only 26.1% of participants with migraine met their recommended dietary allowance (RDA) for magnesium through diet and supplements. Attainment of the RDA for magnesium through diet and supplements was associated with lower odds of migraine (adjusted odds ratio, 0.83; P = .035).
Study details: An analysis of cross-sectional data of 3,626 individuals aged 20-50 years from the National Health and Nutrition Examination Survey (2001-2004) who were categorized into migraine (n=905) and control (n=2,721) groups.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Slavin M et al. Headache. 2021 Jan 27. doi: 10.1111/head.14065.