Ovarian cancer risk was higher in women with endometriosis overall and markedly increased in those with severe forms, a large population-based cohort study found.

The findings, published in JAMA, suggest these women may benefit from counseling on ovarian cancer risk and prevention and potentially from targeted screening, according to a group led by Mollie E. Barnard, ScD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

While the absolute increase in number of cases was small, endometriosis patients overall had a more than fourfold higher risk for any type of ovarian cancer. Those with more severe forms, such as ovarian endometriomas or deep infiltrating endometriosis, had a nearly 10-fold higher risk of any type of ovarian cancer. In addition, those with more severe endometriosis had a 19-fold higher risk of type 1 (slow-growing) ovarian cancer and almost three times the risk of the more aggressive type 2.

“Given the rarity of ovarian cancer, the excess risk was relatively small, with 10-20 additional cases per 10,000 women. Nevertheless, women with endometriosis, notably the more severe subtypes, may be an important population for targeted cancer screening and prevention studies,” said corresponding author Karen C. Schliep, PhD, MSPH, associate professor in the university’s Division of Public Health.

Prior studies have shown modest associations between endometriosis and ovarian cancer, Dr. Schliep said in an interview. A 2021 systematic review and meta-analysis found endometriosis conferred nearly double the risk of ovarian cancer, although associations varied by ovarian cancer histotype. Few studies have been large enough to assess associations between endometriosis types — including superficial or peritoneal endometriosis vs ovarian endometriomas or deep infiltrating endometriosis and ovarian cancer histotypes such as low-grade serous, endometrioid, clear cell, and mucinous carcinomas (type 1), and the most aggressive and lethal form, high-grade serous type 2, she said in an interview. “Our large health administrative database of over 11 million individuals with linked electronic health and cancer registry data allowed us to answer this as yet poorly studied research question.”
 

Study Details

Drawing on Utah electronic health records from 1992 to 2019, the investigators matched 78,893 women with endometriosis in a 1:5 ratio to unaffected women. Cases were categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other, and the types of endometriosis were matched to ovarian cancer histotypes.

The mean age of patients at first endometriosis diagnosis was 36 and the mean follow-up was 12 years. Compared with controls, endometriosis patients were more likely to be nulliparous (31% vs 24%) and to have had a hysterectomy (39% vs 6%) during follow-up.

There were 596 reported cases of ovarian cancer in the cohort. Those with incident endometriosis were 4.2 times more likely to develop ovarian cancer (95% CI, 3.59-4.91), 7.48 times more likely to develop type 1 ovarian cancer (95% CI, 5.80-9.65), and 2.70 times more likely to develop type 2 ovarian cancer (95% CI, 2.09-3.49) compared with those without endometriosis.

The magnitudes of these associations varied by endometriosis subtype. Individuals diagnosed with deep infiltrating endometriosis and/or ovarian endometriomas had 9.66 times the risk of ovarian cancer vs individuals without endometriosis (95% CI, 7.77-12.00). “Women with, compared to without, more severe endometriosis had a 19-fold higher risk of type 1 ovarian cancer, including endometrioid, clear cell, mucinous, and low-grade serous,” Dr. Schliep said, with associated risk highest for malignant subtypes such as clear cell and endometrioid carcinoma (adjusted hazard ratios, 11.15 and 7.96, respectively.

According to Dr. Schliep, physicians should encourage endometriosis patients to be aware of but not worry about ovarian cancer risk because the likelihood of developing it remains low. For their part, patients can reduce their risk of cancer through a balanced diet with low intake of alcohol, regular exercise, a healthy weight, and abstention from smoking.

Her message for researchers is as follows: “We need more studies that explore how different types of endometriosis impact different types of ovarian cancer risk. These studies will guide improved ovarian cancer screening and prevention strategies among women with severe endometriosis, with or without other important ovarian cancer risk factors such as BRCA 1/2 variations.”

An accompanying editorial called the Utah study “eloquent” and noted its distinguishing contribution of observing associations between subtypes of endometriosis with overall risk for ovarian cancer as well as histologic subtypes of epithelial ovarian cancer.

Nevertheless, Michael T. McHale, MD, of the Department of Obstetrics, Gynecology, and Reproductive Sciences at Moores Cancer Center, UC San Diego Health, University of California, expressed some methodological concerns. Although the authors attempted to control for key confounders, he noted, the dataset could not provide details on the medical management of endometriosis, such as oral contraceptives or gonadotropin-releasing hormone agonists. “Additionally, there is a possibility that women in the control cohort could have had undiagnosed endometriosis,” he wrote.

Furthermore, making clinical recommendations from these reported observations, particularly with respect to deep infiltrating endometriosis, would require a clear and consistent definition of this type in the dataset over the entire study interval from 1992 to 2019 and for the state of Utah, which the authors did not provide.

“Despite this potential challenge, the increased risk associated with deep infiltrating and/or ovarian endometriosis was clearly significant,” Dr. McHale wrote.

And although the absolute number of ovarian cancers is limited, in his view, the increased risk is sufficiently significant to advise women who have completed childbearing or have alternative fertility options to consider “more definitive surgery.”

This study was supported by multiple not-for-profit agencies, including the National Cancer Institute, the University of Utah, the National Center for Research Resources, the Utah Department of Health and Human Services, the Utah Cancer Registry, the US Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, the National Institutes of Health, and Doris Duke Foundation. Dr. Barnard reported grants from the National Cancer Institute during the conduct of the study and personal fees from Epi Excellence LLC outside the submitted work. Other coauthors reported similar funding from nonprofit agencies or private research organizations. Dr Schliep disclosed no competing interests. Dr McHale reported educational consulting for Eisai Training outside the submitted work.

Ovarian cancer risk was higher in women with endometriosis overall and markedly increased in those with severe forms, a large population-based cohort study found.

The findings, published in JAMA, suggest these women may benefit from counseling on ovarian cancer risk and prevention and potentially from targeted screening, according to a group led by Mollie E. Barnard, ScD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

While the absolute increase in number of cases was small, endometriosis patients overall had a more than fourfold higher risk for any type of ovarian cancer. Those with more severe forms, such as ovarian endometriomas or deep infiltrating endometriosis, had a nearly 10-fold higher risk of any type of ovarian cancer. In addition, those with more severe endometriosis had a 19-fold higher risk of type 1 (slow-growing) ovarian cancer and almost three times the risk of the more aggressive type 2.

“Given the rarity of ovarian cancer, the excess risk was relatively small, with 10-20 additional cases per 10,000 women. Nevertheless, women with endometriosis, notably the more severe subtypes, may be an important population for targeted cancer screening and prevention studies,” said corresponding author Karen C. Schliep, PhD, MSPH, associate professor in the university’s Division of Public Health.

Prior studies have shown modest associations between endometriosis and ovarian cancer, Dr. Schliep said in an interview. A 2021 systematic review and meta-analysis found endometriosis conferred nearly double the risk of ovarian cancer, although associations varied by ovarian cancer histotype. Few studies have been large enough to assess associations between endometriosis types — including superficial or peritoneal endometriosis vs ovarian endometriomas or deep infiltrating endometriosis and ovarian cancer histotypes such as low-grade serous, endometrioid, clear cell, and mucinous carcinomas (type 1), and the most aggressive and lethal form, high-grade serous type 2, she said in an interview. “Our large health administrative database of over 11 million individuals with linked electronic health and cancer registry data allowed us to answer this as yet poorly studied research question.”
 

Study Details

Drawing on Utah electronic health records from 1992 to 2019, the investigators matched 78,893 women with endometriosis in a 1:5 ratio to unaffected women. Cases were categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other, and the types of endometriosis were matched to ovarian cancer histotypes.

The mean age of patients at first endometriosis diagnosis was 36 and the mean follow-up was 12 years. Compared with controls, endometriosis patients were more likely to be nulliparous (31% vs 24%) and to have had a hysterectomy (39% vs 6%) during follow-up.

There were 596 reported cases of ovarian cancer in the cohort. Those with incident endometriosis were 4.2 times more likely to develop ovarian cancer (95% CI, 3.59-4.91), 7.48 times more likely to develop type 1 ovarian cancer (95% CI, 5.80-9.65), and 2.70 times more likely to develop type 2 ovarian cancer (95% CI, 2.09-3.49) compared with those without endometriosis.

The magnitudes of these associations varied by endometriosis subtype. Individuals diagnosed with deep infiltrating endometriosis and/or ovarian endometriomas had 9.66 times the risk of ovarian cancer vs individuals without endometriosis (95% CI, 7.77-12.00). “Women with, compared to without, more severe endometriosis had a 19-fold higher risk of type 1 ovarian cancer, including endometrioid, clear cell, mucinous, and low-grade serous,” Dr. Schliep said, with associated risk highest for malignant subtypes such as clear cell and endometrioid carcinoma (adjusted hazard ratios, 11.15 and 7.96, respectively.

According to Dr. Schliep, physicians should encourage endometriosis patients to be aware of but not worry about ovarian cancer risk because the likelihood of developing it remains low. For their part, patients can reduce their risk of cancer through a balanced diet with low intake of alcohol, regular exercise, a healthy weight, and abstention from smoking.

Her message for researchers is as follows: “We need more studies that explore how different types of endometriosis impact different types of ovarian cancer risk. These studies will guide improved ovarian cancer screening and prevention strategies among women with severe endometriosis, with or without other important ovarian cancer risk factors such as BRCA 1/2 variations.”

An accompanying editorial called the Utah study “eloquent” and noted its distinguishing contribution of observing associations between subtypes of endometriosis with overall risk for ovarian cancer as well as histologic subtypes of epithelial ovarian cancer.

Nevertheless, Michael T. McHale, MD, of the Department of Obstetrics, Gynecology, and Reproductive Sciences at Moores Cancer Center, UC San Diego Health, University of California, expressed some methodological concerns. Although the authors attempted to control for key confounders, he noted, the dataset could not provide details on the medical management of endometriosis, such as oral contraceptives or gonadotropin-releasing hormone agonists. “Additionally, there is a possibility that women in the control cohort could have had undiagnosed endometriosis,” he wrote.

Furthermore, making clinical recommendations from these reported observations, particularly with respect to deep infiltrating endometriosis, would require a clear and consistent definition of this type in the dataset over the entire study interval from 1992 to 2019 and for the state of Utah, which the authors did not provide.

“Despite this potential challenge, the increased risk associated with deep infiltrating and/or ovarian endometriosis was clearly significant,” Dr. McHale wrote.

And although the absolute number of ovarian cancers is limited, in his view, the increased risk is sufficiently significant to advise women who have completed childbearing or have alternative fertility options to consider “more definitive surgery.”

This study was supported by multiple not-for-profit agencies, including the National Cancer Institute, the University of Utah, the National Center for Research Resources, the Utah Department of Health and Human Services, the Utah Cancer Registry, the US Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, the National Institutes of Health, and Doris Duke Foundation. Dr. Barnard reported grants from the National Cancer Institute during the conduct of the study and personal fees from Epi Excellence LLC outside the submitted work. Other coauthors reported similar funding from nonprofit agencies or private research organizations. Dr Schliep disclosed no competing interests. Dr McHale reported educational consulting for Eisai Training outside the submitted work.

Ovarian cancer risk was higher in women with endometriosis overall and markedly increased in those with severe forms, a large population-based cohort study found.

The findings, published in JAMA, suggest these women may benefit from counseling on ovarian cancer risk and prevention and potentially from targeted screening, according to a group led by Mollie E. Barnard, ScD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

While the absolute increase in number of cases was small, endometriosis patients overall had a more than fourfold higher risk for any type of ovarian cancer. Those with more severe forms, such as ovarian endometriomas or deep infiltrating endometriosis, had a nearly 10-fold higher risk of any type of ovarian cancer. In addition, those with more severe endometriosis had a 19-fold higher risk of type 1 (slow-growing) ovarian cancer and almost three times the risk of the more aggressive type 2.

“Given the rarity of ovarian cancer, the excess risk was relatively small, with 10-20 additional cases per 10,000 women. Nevertheless, women with endometriosis, notably the more severe subtypes, may be an important population for targeted cancer screening and prevention studies,” said corresponding author Karen C. Schliep, PhD, MSPH, associate professor in the university’s Division of Public Health.

Prior studies have shown modest associations between endometriosis and ovarian cancer, Dr. Schliep said in an interview. A 2021 systematic review and meta-analysis found endometriosis conferred nearly double the risk of ovarian cancer, although associations varied by ovarian cancer histotype. Few studies have been large enough to assess associations between endometriosis types — including superficial or peritoneal endometriosis vs ovarian endometriomas or deep infiltrating endometriosis and ovarian cancer histotypes such as low-grade serous, endometrioid, clear cell, and mucinous carcinomas (type 1), and the most aggressive and lethal form, high-grade serous type 2, she said in an interview. “Our large health administrative database of over 11 million individuals with linked electronic health and cancer registry data allowed us to answer this as yet poorly studied research question.”
 

Study Details

Drawing on Utah electronic health records from 1992 to 2019, the investigators matched 78,893 women with endometriosis in a 1:5 ratio to unaffected women. Cases were categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other, and the types of endometriosis were matched to ovarian cancer histotypes.

The mean age of patients at first endometriosis diagnosis was 36 and the mean follow-up was 12 years. Compared with controls, endometriosis patients were more likely to be nulliparous (31% vs 24%) and to have had a hysterectomy (39% vs 6%) during follow-up.

There were 596 reported cases of ovarian cancer in the cohort. Those with incident endometriosis were 4.2 times more likely to develop ovarian cancer (95% CI, 3.59-4.91), 7.48 times more likely to develop type 1 ovarian cancer (95% CI, 5.80-9.65), and 2.70 times more likely to develop type 2 ovarian cancer (95% CI, 2.09-3.49) compared with those without endometriosis.

The magnitudes of these associations varied by endometriosis subtype. Individuals diagnosed with deep infiltrating endometriosis and/or ovarian endometriomas had 9.66 times the risk of ovarian cancer vs individuals without endometriosis (95% CI, 7.77-12.00). “Women with, compared to without, more severe endometriosis had a 19-fold higher risk of type 1 ovarian cancer, including endometrioid, clear cell, mucinous, and low-grade serous,” Dr. Schliep said, with associated risk highest for malignant subtypes such as clear cell and endometrioid carcinoma (adjusted hazard ratios, 11.15 and 7.96, respectively.

According to Dr. Schliep, physicians should encourage endometriosis patients to be aware of but not worry about ovarian cancer risk because the likelihood of developing it remains low. For their part, patients can reduce their risk of cancer through a balanced diet with low intake of alcohol, regular exercise, a healthy weight, and abstention from smoking.

Her message for researchers is as follows: “We need more studies that explore how different types of endometriosis impact different types of ovarian cancer risk. These studies will guide improved ovarian cancer screening and prevention strategies among women with severe endometriosis, with or without other important ovarian cancer risk factors such as BRCA 1/2 variations.”

An accompanying editorial called the Utah study “eloquent” and noted its distinguishing contribution of observing associations between subtypes of endometriosis with overall risk for ovarian cancer as well as histologic subtypes of epithelial ovarian cancer.

Nevertheless, Michael T. McHale, MD, of the Department of Obstetrics, Gynecology, and Reproductive Sciences at Moores Cancer Center, UC San Diego Health, University of California, expressed some methodological concerns. Although the authors attempted to control for key confounders, he noted, the dataset could not provide details on the medical management of endometriosis, such as oral contraceptives or gonadotropin-releasing hormone agonists. “Additionally, there is a possibility that women in the control cohort could have had undiagnosed endometriosis,” he wrote.

Furthermore, making clinical recommendations from these reported observations, particularly with respect to deep infiltrating endometriosis, would require a clear and consistent definition of this type in the dataset over the entire study interval from 1992 to 2019 and for the state of Utah, which the authors did not provide.

“Despite this potential challenge, the increased risk associated with deep infiltrating and/or ovarian endometriosis was clearly significant,” Dr. McHale wrote.

And although the absolute number of ovarian cancers is limited, in his view, the increased risk is sufficiently significant to advise women who have completed childbearing or have alternative fertility options to consider “more definitive surgery.”

This study was supported by multiple not-for-profit agencies, including the National Cancer Institute, the University of Utah, the National Center for Research Resources, the Utah Department of Health and Human Services, the Utah Cancer Registry, the US Centers for Disease Control and Prevention, the Huntsman Cancer Foundation, the National Institutes of Health, and Doris Duke Foundation. Dr. Barnard reported grants from the National Cancer Institute during the conduct of the study and personal fees from Epi Excellence LLC outside the submitted work. Other coauthors reported similar funding from nonprofit agencies or private research organizations. Dr Schliep disclosed no competing interests. Dr McHale reported educational consulting for Eisai Training outside the submitted work.

Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.

The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.

The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).

In many ways I agree with this. No-shows are a waste of time and money for every medical practice. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.

Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.

Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.

$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.

Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.

But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.

The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.

The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).

In many ways I agree with this. No-shows are a waste of time and money for every medical practice. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.

Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.

Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.

$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.

Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.

But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Earlier in 2024 the French government proposed fining patients €5 ($5.36 at the time of writing) for no-show doctor appointments.

The rationale is that there are 27 million missed medical appointments annually in France (just based on population size, I’d guess it’s higher in the United States) and that they not only waste time, but also keep people who need to be seen sooner from getting in.

The penalty wouldn’t be automatic, and it’s up to the physician to decide if a patient’s excuse is valid. As I understand it, the €5 is paid as a fine to the national healthcare service, and not to the physician (I may be wrong on that).

In many ways I agree with this. No-shows are a waste of time and money for every medical practice. Given the patchwork of regulations and insurance rules we face in the United States, it’s almost impossible to penalize patients for missed visits unless you don’t take insurance at all.

Some people have legitimate reasons for no-showing. Cars break, family emergencies happen, storms roll in. Even the most punctual of us sometimes just space on something. If someone calls in at the last minute to say “I can’t make it” I’m more forgiving than if we never hear from them at all. That’s why it’s good to have the doctors, who know the people they’re dealing with, make the final call.

Of course, there are those who will just lie and make up an excuse, and sometimes it’s tricky to know who is or isn’t worth penalizing. Some people just don’t care, or are dishonest, or both.

$5.36 isn’t a huge amount for most. But it’s still symbolic. It forces people to, as they say, “have skin in the game.” Yes, they may still have a copay, but that’s only paid if they show up. This puts them in the position of being penalized for thoughtlessness.

Is it a great idea? Not really. I suspect most of us would dismiss it rather than fight with the patient.

But there aren’t any easy answers, and I’d like to see how, if they go ahead with the proposal, it plays out. If it works, I hope we won’t be too far behind.

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

TOPLINE: 

Spironolactone may benefit women of childbearing age with mild hidradenitis suppurativa (HS), especially if initiated early, according to the results of a single-center retrospective study.

METHODOLOGY:

• This retrospective study included 157 women (median age, 36.5 years) with HS who received spironolactone for at least 3 months between 2000 and 2021 at Michigan Medicine outpatient dermatology clinics. The majority of patients were White (59%) or Black (37%) individuals.
• The median prescribed dose was 100 mg/d, the most common dose was 50-100 mg/d, and the median time spironolactone was initiated was 8.8 years after HS was diagnosed.
• Improvement status was classified on the basis of objective clinician assessments, including documented reductions in the lesion count, pain, and symptoms.

TAKEAWAY:

• Overall, 31 patients (20%) showed improvements with spironolactone treatment.
• A shorter duration between the diagnosis of HS and the initiation of spironolactone was associated with improvement (P = .047).
• Axillary involvement (P = .003), the use of intralesional steroids (P = .015), previous treatments (P = .023), and previous treatment failures (P = .030) were linked to a lack of improvement with spironolactone.
• Patients with Hurley stage III were 85% less likely to experience improvement with spironolactone (P = .036).

IN PRACTICE:

Spironolactone, which has antiandrogenic properties, “may be beneficial for patients with mild HS, notably those at Hurley stage I if implemented early as a primary or ancillary treatment,” the authors concluded, adding that prospective, multicenter studies are needed to “elucidate further the safety and efficacy of spironolactone for treating HS.”

SOURCE:

The study was led by Suma V. Gangidi, BS, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, and was published online in the International Journal of Women’s Dermatology.

LIMITATIONS:

Retrospective design can introduce inherent biases, including the potential for missing or misclassified data. Additionally, the study was conducted at a single center, which may limit the generalizability, and findings were also limited by lack of standardized objective measures for assessing treatment improvement, presence of confounding variables from concomitant treatments, small sample size, and potential multicollinearity.

DISCLOSURES:

This study did not receive any funding. One author declared ties with various pharmaceutical companies. The other authors declared no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Spironolactone may benefit women of childbearing age with mild hidradenitis suppurativa (HS), especially if initiated early, according to the results of a single-center retrospective study.

METHODOLOGY:

• This retrospective study included 157 women (median age, 36.5 years) with HS who received spironolactone for at least 3 months between 2000 and 2021 at Michigan Medicine outpatient dermatology clinics. The majority of patients were White (59%) or Black (37%) individuals.
• The median prescribed dose was 100 mg/d, the most common dose was 50-100 mg/d, and the median time spironolactone was initiated was 8.8 years after HS was diagnosed.
• Improvement status was classified on the basis of objective clinician assessments, including documented reductions in the lesion count, pain, and symptoms.

TAKEAWAY:

• Overall, 31 patients (20%) showed improvements with spironolactone treatment.
• A shorter duration between the diagnosis of HS and the initiation of spironolactone was associated with improvement (P = .047).
• Axillary involvement (P = .003), the use of intralesional steroids (P = .015), previous treatments (P = .023), and previous treatment failures (P = .030) were linked to a lack of improvement with spironolactone.
• Patients with Hurley stage III were 85% less likely to experience improvement with spironolactone (P = .036).

IN PRACTICE:

Spironolactone, which has antiandrogenic properties, “may be beneficial for patients with mild HS, notably those at Hurley stage I if implemented early as a primary or ancillary treatment,” the authors concluded, adding that prospective, multicenter studies are needed to “elucidate further the safety and efficacy of spironolactone for treating HS.”

SOURCE:

The study was led by Suma V. Gangidi, BS, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, and was published online in the International Journal of Women’s Dermatology.

LIMITATIONS:

Retrospective design can introduce inherent biases, including the potential for missing or misclassified data. Additionally, the study was conducted at a single center, which may limit the generalizability, and findings were also limited by lack of standardized objective measures for assessing treatment improvement, presence of confounding variables from concomitant treatments, small sample size, and potential multicollinearity.

DISCLOSURES:

This study did not receive any funding. One author declared ties with various pharmaceutical companies. The other authors declared no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Spironolactone may benefit women of childbearing age with mild hidradenitis suppurativa (HS), especially if initiated early, according to the results of a single-center retrospective study.

METHODOLOGY:

• This retrospective study included 157 women (median age, 36.5 years) with HS who received spironolactone for at least 3 months between 2000 and 2021 at Michigan Medicine outpatient dermatology clinics. The majority of patients were White (59%) or Black (37%) individuals.
• The median prescribed dose was 100 mg/d, the most common dose was 50-100 mg/d, and the median time spironolactone was initiated was 8.8 years after HS was diagnosed.
• Improvement status was classified on the basis of objective clinician assessments, including documented reductions in the lesion count, pain, and symptoms.

TAKEAWAY:

• Overall, 31 patients (20%) showed improvements with spironolactone treatment.
• A shorter duration between the diagnosis of HS and the initiation of spironolactone was associated with improvement (P = .047).
• Axillary involvement (P = .003), the use of intralesional steroids (P = .015), previous treatments (P = .023), and previous treatment failures (P = .030) were linked to a lack of improvement with spironolactone.
• Patients with Hurley stage III were 85% less likely to experience improvement with spironolactone (P = .036).

IN PRACTICE:

Spironolactone, which has antiandrogenic properties, “may be beneficial for patients with mild HS, notably those at Hurley stage I if implemented early as a primary or ancillary treatment,” the authors concluded, adding that prospective, multicenter studies are needed to “elucidate further the safety and efficacy of spironolactone for treating HS.”

SOURCE:

The study was led by Suma V. Gangidi, BS, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, and was published online in the International Journal of Women’s Dermatology.

LIMITATIONS:

Retrospective design can introduce inherent biases, including the potential for missing or misclassified data. Additionally, the study was conducted at a single center, which may limit the generalizability, and findings were also limited by lack of standardized objective measures for assessing treatment improvement, presence of confounding variables from concomitant treatments, small sample size, and potential multicollinearity.

DISCLOSURES:

This study did not receive any funding. One author declared ties with various pharmaceutical companies. The other authors declared no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Dupilumab treatment significantly improved both hair regrowth and the severity of atopic dermatitis (AD) in pediatric patients who also had alopecia areata (AA) in a review. 

METHODOLOGY:

• Researchers conducted a scoping review of seven studies, a result of a MEDLINE and Embase search on March 1, 2024, which included 31 patients aged 4-17 years with both AD and AA (average age, 11.4 years; 64.5% women).
• The review included four case reports, two case series, and one retrospective chart review.
• Patients had an average duration of AA and AD of 3.31 years and 5.33 years, respectively, before starting dupilumab.
• The type of AA was listed in 22 patients; among these patients, alopecia universalis was the most common (50%), followed by alopecia ophiasis (22.7%), patchy alopecia (18.2%), and alopecia totalis (9.09%).

TAKEAWAY:

• Overall, 77.4% of patients in the trials achieved hair regrowth with dupilumab treatment with a mean 42.6 reduction in SALT score (measuring scalp hair loss on a scale of 0-100) over an average of 3.21 months (P < .01).
• Severity of AD was reduced by an average of 2.14 units to an average of 0.857 (clear or almost clear AD; P < .01) on the AD Investigator Global Assessment dropping from an average of 3 (severe disease) before treatment.
• There were no characteristics that significantly distinguished patients with AA who responded to treatment from those who did not.
• Four patients reported worsening of preexisting AA after starting dupilumab; two of these continued dupilumab and showed improvement at subsequent follow-ups.

IN PRACTICE:

“Our review highlights the efficacy of dupilumab in pediatric AA with concurrent AD,” wrote the authors, noting that “the exact mechanism for this efficacy remains speculative.” Although there have been reports of new or worsening AA with dupilumab, they added, its “favorable safety profile in pediatrics enhances its appeal for AA treatment, as monotherapy or in combination with other AA medications.” 

SOURCE:

The study was led by Dea Metko, Michael G. DeGroote School of Medicine in Hamilton, Ontario, Canada. It was published online on July 4, 2024, in Pediatric Dermatology. 

LIMITATIONS:

Potential publication bias, inconsistent data reporting, the small number of patients, and short follow-up duration were the main limitations of this study.

DISCLOSURES:

The study funding source was not disclosed. One author received honoraria outside this work. Other authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Dupilumab treatment significantly improved both hair regrowth and the severity of atopic dermatitis (AD) in pediatric patients who also had alopecia areata (AA) in a review. 

METHODOLOGY:

• Researchers conducted a scoping review of seven studies, a result of a MEDLINE and Embase search on March 1, 2024, which included 31 patients aged 4-17 years with both AD and AA (average age, 11.4 years; 64.5% women).
• The review included four case reports, two case series, and one retrospective chart review.
• Patients had an average duration of AA and AD of 3.31 years and 5.33 years, respectively, before starting dupilumab.
• The type of AA was listed in 22 patients; among these patients, alopecia universalis was the most common (50%), followed by alopecia ophiasis (22.7%), patchy alopecia (18.2%), and alopecia totalis (9.09%).

TAKEAWAY:

• Overall, 77.4% of patients in the trials achieved hair regrowth with dupilumab treatment with a mean 42.6 reduction in SALT score (measuring scalp hair loss on a scale of 0-100) over an average of 3.21 months (P < .01).
• Severity of AD was reduced by an average of 2.14 units to an average of 0.857 (clear or almost clear AD; P < .01) on the AD Investigator Global Assessment dropping from an average of 3 (severe disease) before treatment.
• There were no characteristics that significantly distinguished patients with AA who responded to treatment from those who did not.
• Four patients reported worsening of preexisting AA after starting dupilumab; two of these continued dupilumab and showed improvement at subsequent follow-ups.

IN PRACTICE:

“Our review highlights the efficacy of dupilumab in pediatric AA with concurrent AD,” wrote the authors, noting that “the exact mechanism for this efficacy remains speculative.” Although there have been reports of new or worsening AA with dupilumab, they added, its “favorable safety profile in pediatrics enhances its appeal for AA treatment, as monotherapy or in combination with other AA medications.” 

SOURCE:

The study was led by Dea Metko, Michael G. DeGroote School of Medicine in Hamilton, Ontario, Canada. It was published online on July 4, 2024, in Pediatric Dermatology. 

LIMITATIONS:

Potential publication bias, inconsistent data reporting, the small number of patients, and short follow-up duration were the main limitations of this study.

DISCLOSURES:

The study funding source was not disclosed. One author received honoraria outside this work. Other authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Dupilumab treatment significantly improved both hair regrowth and the severity of atopic dermatitis (AD) in pediatric patients who also had alopecia areata (AA) in a review. 

METHODOLOGY:

• Researchers conducted a scoping review of seven studies, a result of a MEDLINE and Embase search on March 1, 2024, which included 31 patients aged 4-17 years with both AD and AA (average age, 11.4 years; 64.5% women).
• The review included four case reports, two case series, and one retrospective chart review.
• Patients had an average duration of AA and AD of 3.31 years and 5.33 years, respectively, before starting dupilumab.
• The type of AA was listed in 22 patients; among these patients, alopecia universalis was the most common (50%), followed by alopecia ophiasis (22.7%), patchy alopecia (18.2%), and alopecia totalis (9.09%).

TAKEAWAY:

• Overall, 77.4% of patients in the trials achieved hair regrowth with dupilumab treatment with a mean 42.6 reduction in SALT score (measuring scalp hair loss on a scale of 0-100) over an average of 3.21 months (P < .01).
• Severity of AD was reduced by an average of 2.14 units to an average of 0.857 (clear or almost clear AD; P < .01) on the AD Investigator Global Assessment dropping from an average of 3 (severe disease) before treatment.
• There were no characteristics that significantly distinguished patients with AA who responded to treatment from those who did not.
• Four patients reported worsening of preexisting AA after starting dupilumab; two of these continued dupilumab and showed improvement at subsequent follow-ups.

IN PRACTICE:

“Our review highlights the efficacy of dupilumab in pediatric AA with concurrent AD,” wrote the authors, noting that “the exact mechanism for this efficacy remains speculative.” Although there have been reports of new or worsening AA with dupilumab, they added, its “favorable safety profile in pediatrics enhances its appeal for AA treatment, as monotherapy or in combination with other AA medications.” 

SOURCE:

The study was led by Dea Metko, Michael G. DeGroote School of Medicine in Hamilton, Ontario, Canada. It was published online on July 4, 2024, in Pediatric Dermatology. 

LIMITATIONS:

Potential publication bias, inconsistent data reporting, the small number of patients, and short follow-up duration were the main limitations of this study.

DISCLOSURES:

The study funding source was not disclosed. One author received honoraria outside this work. Other authors declared no conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Seborrheic dermatitis affects an estimated 4% of the global population, with significant variations across age groups, settings, and regions, according to a meta-analysis that also found a higher prevalence in adults than in children.

METHODOLOGY:

• Researchers conducted a meta-analysis of 121 studies, which included 1,260,163 people with clinician-diagnosed seborrheic dermatitis.
• The included studies represented nine countries; most were from India (n = 18), Turkey (n = 13), and the United States (n = 8).
• The primary outcome was the pooled prevalence of seborrheic dermatitis.

TAKEAWAY:

• The overall pooled prevalence of seborrheic dermatitis was 4.38%, 4.08% in clinical settings, and 4.71% in the studies conducted in the general population.
• The prevalence of seborrheic dermatitis was higher among adults (5.64%) than in children (3.7%) and neonates (0.23%).
• A significant variation was observed across countries, with South Africa having the highest prevalence at 8.82%, followed by the United States at 5.86% and Turkey at 3.74%, while India had the lowest prevalence at 2.62%.

IN PRACTICE:

The global prevalence in this meta-analysis was “higher than previous large-scale global estimates, with notable geographic and sociodemographic variability, highlighting the potential impact of environmental factors and cultural practices,” the authors wrote.

SOURCE:

The study was led by Meredith Tyree Polaskey, MS, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, and was published online on July 3, 2024, in the JAMA Dermatology.

LIMITATIONS:

Interpretation of the findings is limited by research gaps in Central Asia, much of Sub-Saharan Africa, Eastern Europe, Southeast Asia, Latin America (excluding Brazil), and the Caribbean, along with potential underreporting in regions with restricted healthcare access and significant heterogeneity across studies.

DISCLOSURES:

Funding information was not available. One author reported serving as an advisor, consultant, speaker, and/or investigator for multiple pharmaceutical companies, including AbbVie, Amgen, and Pfizer.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Seborrheic dermatitis affects an estimated 4% of the global population, with significant variations across age groups, settings, and regions, according to a meta-analysis that also found a higher prevalence in adults than in children.

METHODOLOGY:

• Researchers conducted a meta-analysis of 121 studies, which included 1,260,163 people with clinician-diagnosed seborrheic dermatitis.
• The included studies represented nine countries; most were from India (n = 18), Turkey (n = 13), and the United States (n = 8).
• The primary outcome was the pooled prevalence of seborrheic dermatitis.

TAKEAWAY:

• The overall pooled prevalence of seborrheic dermatitis was 4.38%, 4.08% in clinical settings, and 4.71% in the studies conducted in the general population.
• The prevalence of seborrheic dermatitis was higher among adults (5.64%) than in children (3.7%) and neonates (0.23%).
• A significant variation was observed across countries, with South Africa having the highest prevalence at 8.82%, followed by the United States at 5.86% and Turkey at 3.74%, while India had the lowest prevalence at 2.62%.

IN PRACTICE:

The global prevalence in this meta-analysis was “higher than previous large-scale global estimates, with notable geographic and sociodemographic variability, highlighting the potential impact of environmental factors and cultural practices,” the authors wrote.

SOURCE:

The study was led by Meredith Tyree Polaskey, MS, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, and was published online on July 3, 2024, in the JAMA Dermatology.

LIMITATIONS:

Interpretation of the findings is limited by research gaps in Central Asia, much of Sub-Saharan Africa, Eastern Europe, Southeast Asia, Latin America (excluding Brazil), and the Caribbean, along with potential underreporting in regions with restricted healthcare access and significant heterogeneity across studies.

DISCLOSURES:

Funding information was not available. One author reported serving as an advisor, consultant, speaker, and/or investigator for multiple pharmaceutical companies, including AbbVie, Amgen, and Pfizer.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Seborrheic dermatitis affects an estimated 4% of the global population, with significant variations across age groups, settings, and regions, according to a meta-analysis that also found a higher prevalence in adults than in children.

METHODOLOGY:

• Researchers conducted a meta-analysis of 121 studies, which included 1,260,163 people with clinician-diagnosed seborrheic dermatitis.
• The included studies represented nine countries; most were from India (n = 18), Turkey (n = 13), and the United States (n = 8).
• The primary outcome was the pooled prevalence of seborrheic dermatitis.

TAKEAWAY:

• The overall pooled prevalence of seborrheic dermatitis was 4.38%, 4.08% in clinical settings, and 4.71% in the studies conducted in the general population.
• The prevalence of seborrheic dermatitis was higher among adults (5.64%) than in children (3.7%) and neonates (0.23%).
• A significant variation was observed across countries, with South Africa having the highest prevalence at 8.82%, followed by the United States at 5.86% and Turkey at 3.74%, while India had the lowest prevalence at 2.62%.

IN PRACTICE:

The global prevalence in this meta-analysis was “higher than previous large-scale global estimates, with notable geographic and sociodemographic variability, highlighting the potential impact of environmental factors and cultural practices,” the authors wrote.

SOURCE:

The study was led by Meredith Tyree Polaskey, MS, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, and was published online on July 3, 2024, in the JAMA Dermatology.

LIMITATIONS:

Interpretation of the findings is limited by research gaps in Central Asia, much of Sub-Saharan Africa, Eastern Europe, Southeast Asia, Latin America (excluding Brazil), and the Caribbean, along with potential underreporting in regions with restricted healthcare access and significant heterogeneity across studies.

DISCLOSURES:

Funding information was not available. One author reported serving as an advisor, consultant, speaker, and/or investigator for multiple pharmaceutical companies, including AbbVie, Amgen, and Pfizer.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

• Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
• Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
• Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
• Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
• Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

• None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
• Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
• Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
• The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

• Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
• Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
• Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
• Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
• Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

• None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
• Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
• Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
• The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Full-term afebrile infants with pustules and vesicles have a low likelihood of life-threatening infections once herpes simplex virus (HSV) is ruled out, according to the findings from a retrospective study.

METHODOLOGY:

• Researchers reviewed the electronic medical records of infants aged ≤ 60 days who received a pediatric dermatology consultation at six US academic institutions between September 2013 and August 2019.
• Among 879 consults, 183 afebrile infants were identified as having presented with pustules, vesicles, and/or bullae.
• Infectious disease workups included blood cultures, urine cultures, lumbar punctures, and HSV testing using viral skin culture, direct immunofluorescence assay, and/or polymerase chain reaction.
• Patients were categorized by gestational age as preterm (< 37 weeks), full-term (37-42 weeks), and post-term (≥ 42 weeks).
• Overall, 67.8% of infants had pustules, 31.1% had vesicles, and 10.4% had bullae.

TAKEAWAY:

• None of the cases showed positive cerebrospinal fluid or pathogenic blood cultures. In 122 of the cases (66.6%), a noninfectious cause was diagnosed, and an infectious cause was diagnosed in 71 cases (38.8%; some patients had more than one diagnosis).
• Of the 127 newborns evaluated for HSV infection, nine (7.1%) tested positive, of whom seven (5.5%) had disease affecting the skin, eye, and mouth and were full- term infants, and two (1.6%) had disseminated HSV and were preterm infants.
• Angioinvasive fungal infection was diagnosed in five infants (2.7%), all of whom were preterm infants (< 28 weeks gestational age).
• The risk for life-threatening disease was higher in preterm infants born before 32 weeks of gestational age (P < .01) compared with those born after 32 weeks.

IN PRACTICE:

“Full-term, well-appearing, afebrile infants ≤ 60 days of age presenting with pustules or vesicles may not require full SBI [serious bacterial infection] work-up, although larger studies are needed,” the authors concluded. Testing for HSV, they added, “is recommended in all infants with vesicles, grouped pustules, or pustules accompanied by punched out or grouped erosions,” and preterm infants “should be assessed for disseminated fungal infection and HSV in the setting of fluid-filled skin lesions.”

SOURCE:

The study was led by Sonora Yun, BA, Columbia University, New York City, and was published online in Pediatrics.

LIMITATIONS:

The data were limited by the sample size and very low incidence of serious infections. Infants probably had atypical or severe presentations that warranted pediatric dermatology consultation, which may have led to overrepresentation of infectious disease rates. The study inclusion was restricted to those who received a dermatology consult; therefore, the findings may not be generalizable to outpatient primary care.

DISCLOSURES:

This study did not receive any external funding. The authors declared that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

On July 9, the Food and Drug Administration approved the supplemental new drug application for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (AD) in adults and in pediatric patients aged 6 years or older.

Roflumilast cream 0.15%, which has been developed by Arcutis Biotherapeutics and is marketed under the brand name Zoryve, is a steroid-free topical phosphodiesterase-4 inhibitor that was previously approved in a higher concentration to treat seborrheic dermatitis and plaque psoriasis.

According to a press release from Arcutis, approval for AD was supported by positive results from three phase 3 studies, a phase 2 dose-ranging study, and two phase 1 pharmacokinetic trials. In two identical phase 3 studies known as INTEGUMENT-1 and INTEGUMENT-2, about 40% of children and adults treated with roflumilast cream 0.15% achieved a Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) at week 4 (INTEGUMENT-1: 41.5% vs 25.2%; P < .0001; INTEGUMENT-2: 39% vs 16.9%; P < .0001), with significant improvement as early as week 1 (P < .0001).

Among children and adults who participated in the INTEGUMENT studies for 28 and 56 weeks, 61.3% and 65.7% achieved a 75% reduction in their Eczema Area and Severity Index scores, respectively. According to the company, there were no adverse reactions in the combined phase 3 pivotal trials that occurred in more than 2.9% of participants in either arm. The most common adverse reactions included headache (2.9%), nausea (1.9%), application-site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).

The product is expected to be available commercially at the end of July 2024, according to Arcutis. Roflumilast cream 0.3% is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients aged 6 years or older; roflumilast foam 0.3% is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients aged 9 years or older. 

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

On July 9, the Food and Drug Administration approved the supplemental new drug application for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (AD) in adults and in pediatric patients aged 6 years or older.

Roflumilast cream 0.15%, which has been developed by Arcutis Biotherapeutics and is marketed under the brand name Zoryve, is a steroid-free topical phosphodiesterase-4 inhibitor that was previously approved in a higher concentration to treat seborrheic dermatitis and plaque psoriasis.

According to a press release from Arcutis, approval for AD was supported by positive results from three phase 3 studies, a phase 2 dose-ranging study, and two phase 1 pharmacokinetic trials. In two identical phase 3 studies known as INTEGUMENT-1 and INTEGUMENT-2, about 40% of children and adults treated with roflumilast cream 0.15% achieved a Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) at week 4 (INTEGUMENT-1: 41.5% vs 25.2%; P < .0001; INTEGUMENT-2: 39% vs 16.9%; P < .0001), with significant improvement as early as week 1 (P < .0001).

Among children and adults who participated in the INTEGUMENT studies for 28 and 56 weeks, 61.3% and 65.7% achieved a 75% reduction in their Eczema Area and Severity Index scores, respectively. According to the company, there were no adverse reactions in the combined phase 3 pivotal trials that occurred in more than 2.9% of participants in either arm. The most common adverse reactions included headache (2.9%), nausea (1.9%), application-site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).

The product is expected to be available commercially at the end of July 2024, according to Arcutis. Roflumilast cream 0.3% is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients aged 6 years or older; roflumilast foam 0.3% is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients aged 9 years or older. 

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

On July 9, the Food and Drug Administration approved the supplemental new drug application for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (AD) in adults and in pediatric patients aged 6 years or older.

Roflumilast cream 0.15%, which has been developed by Arcutis Biotherapeutics and is marketed under the brand name Zoryve, is a steroid-free topical phosphodiesterase-4 inhibitor that was previously approved in a higher concentration to treat seborrheic dermatitis and plaque psoriasis.

According to a press release from Arcutis, approval for AD was supported by positive results from three phase 3 studies, a phase 2 dose-ranging study, and two phase 1 pharmacokinetic trials. In two identical phase 3 studies known as INTEGUMENT-1 and INTEGUMENT-2, about 40% of children and adults treated with roflumilast cream 0.15% achieved a Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) at week 4 (INTEGUMENT-1: 41.5% vs 25.2%; P < .0001; INTEGUMENT-2: 39% vs 16.9%; P < .0001), with significant improvement as early as week 1 (P < .0001).

Among children and adults who participated in the INTEGUMENT studies for 28 and 56 weeks, 61.3% and 65.7% achieved a 75% reduction in their Eczema Area and Severity Index scores, respectively. According to the company, there were no adverse reactions in the combined phase 3 pivotal trials that occurred in more than 2.9% of participants in either arm. The most common adverse reactions included headache (2.9%), nausea (1.9%), application-site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).

The product is expected to be available commercially at the end of July 2024, according to Arcutis. Roflumilast cream 0.3% is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients aged 6 years or older; roflumilast foam 0.3% is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients aged 9 years or older. 

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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

This transcript has been edited for clarity. 
 

I’m going to tell you the story of two patients with diabetes who had false-positive alcohol tests. 

The first patient is a patient of mine with type 1 diabetes. He was in a car accident. He hit the car in front of him that hit the car in front of them. Because the cars were quite damaged, the police were summoned. 

At the scene, he had a breathalyzer test. He flunked the breathalyzer test, and he was charged with a DUI. The woman in the middle car got out of her car and said her neck hurt. This then rose this to the level of a DUI with injury to one of the other people, and my patient was charged with a felony. He was taken to jail. 

He told them at the scene and at the jail that he had type 1 diabetes. The reason this is so important is because type 1 diabetes can cause a false-positive breathalyzer test. In particular, this patient of mine had not been eating all day long. He’d been getting his basal insulin through the pump, but he had not given any bolus doses of insulin. He was actually quite ketotic.

When he was put in jail, they took away his cell phone so he could no longer see his glucose levels, and they took away the controller for his Omnipod system. He basically had no way to give bolus doses of insulin. Fortunately, the Omnipod system lasted for a day and a half just by giving him basal. The jail physicians did not give him insulin until he’d been in jail for 3 days. 

This is someone with type 1 diabetes, and their protocol for insulin has something to do with high glucose levels and giving something like a sliding scale of insulin. They were not really prepared for managing somebody with type 1 diabetes who was on an automated insulin delivery system. 

I, along with my patient’s parents, worked very hard to get the jail doctors to finally give him Lantus. Inherent in all of this, it made me aware of a number of different issues. The first is that breathalyzer tests can be falsely positive in people with type 1 diabetes if they are ketotic; therefore, people with type 1 diabetes should ask for a blood test to test their alcohol levels if they think it could be a false positive. 

Second, we need to actually figure out a way to help people with type 1 diabetes who happen to be in jail or in prison because if they don’t have access to a smartphone, they’re not going to be able to run their devices. We need to make sure that devices have receivers that can be used, particularly continuous glucose monitors (CGMs), because CGM is the standard of care for patients and should be so for people who are incarcerated. 

The second case is much shorter and isn’t mine, but it was a letter in The New England Journal of Medicine about a man who was on probation, who was having urine tests to show that he had not been consuming alcohol. He was started on empagliflozin, which, interestingly, made his urine test become falsely positive. 

Why? Well, it’s thought it’s because it caused fermentation of the sugar with the bacteria that was in his urine because the people who were processing the sample hadn’t done it correctly, and they kept it out at room temperature for a prolonged period of time before testing it. The urine samples should be kept refrigerated to prevent this from happening. 

These are two people who had false-positive tests because they had diabetes. I think it’s important that we realize that this can happen, and we need to help our patients deal with these situations.

Dr. Peters is professor, Department of Clinical Medicine, Keck School of Medicine; Director, University of Southern California Westside Center for Diabetes, University of Southern California, Los Angeles. She reported conflicts of interest with Abbott Diabetes Care, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, Livongo, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, Zafgen, Dexcom, MannKind, and AstraZeneca.

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

TOPLINE:

An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.

METHODOLOGY:

• Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
• Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
• The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
• Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.

TAKEAWAY:

• Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
• Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
• Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
• Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.

IN PRACTICE:

“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”

The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.

SOURCE:

The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.

LIMITATIONS:

The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.

DISCLOSURES:

This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.

METHODOLOGY:

• Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
• Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
• The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
• Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.

TAKEAWAY:

• Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
• Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
• Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
• Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.

IN PRACTICE:

“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”

The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.

SOURCE:

The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.

LIMITATIONS:

The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.

DISCLOSURES:

This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

An analysis of real-world evidence identified 17 medications, many not previously regarded as potentially hepatotoxic, that have high incidence rates of patient hospitalization for acute liver injury (ALI), offering insights on how to better determine which drugs carry the most significant risk and warrant liver monitoring.

METHODOLOGY:

• Without a systematic approach to classifying medications’ hepatotoxic risk, researchers have used case reports published on the National Institutes of Health’s LiverTox, which doesn’t account for the number of people exposed, to categorize drugs’ likelihood of causing ALI. The objective was to identify the most potentially hepatotoxic medications using real-world incidence rates of severe ALI.
• Researchers analyzed US Department of Veterans Affairs electronic health record data for almost 7.9 million individuals (mean age, 64.4 years; 92.5% men) without preexisting liver or biliary disease who were initiated in an outpatient setting on any one of 194 medications with four or more published reports of hepatotoxicity. Drugs delivered by injection or intravenously, prescribed for alcohol use disorder or liver disease treatment, or used as an anticoagulant were not included in the study.
• The primary outcome measured was hospitalization for severe ALI, defined by alanine aminotransferase levels > 120 U/L and total bilirubin levels > 2.0 mg/dL or the international normalized ratio ≥ 1.5 and total bilirubin levels > 2.0 mg/dL within the first 2 days of admission.
• Researchers organized the medications into groups on the basis of observed rates of severe ALI per 10,000 person-years and classified drugs with 10 or more hospitalizations (group 1) and 5-9.9 hospitalizations (group 2) as the most potentially hepatotoxic. The study period was October 2000 through September 2021.

TAKEAWAY:

• Among the study population, 1739 hospitalizations for severe ALI were identified. Incidence rates of severe ALI varied widely by medication, from 0 to 86.4 events per 10,000 person-years.
• Seventeen medications were classified as the most potentially hepatotoxic (groups 1 and 2). Seven of them (stavudine, erlotinib, lenalidomide or thalidomide, chlorpromazine, metronidazole, prochlorperazine, and isoniazid) had incidence rates of ≥ 10 events per 10,000 person-years. The other 10 medications (moxifloxacin, azathioprine, levofloxacin, clarithromycin, ketoconazole, fluconazole, captopril, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, and ciprofloxacin) showed incidence rates of 5-9.9 events per 10,000 person-years.
• Of the 17 most hepatotoxic medications, 11 (64%) were not classified as highly hepatotoxic in the published case reports, suggesting a discrepancy between real-world data and case report categorizations.
• Similarly, several medications, including some statins, identified as low-risk in this study were classified as among the most hepatotoxic in the published case reports.

IN PRACTICE:

“Categorization of hepatotoxicity based on the number of published case reports did not accurately reflect observed rates of severe ALI (acute liver injury),” the researchers wrote. “This study represents a systematic, reproducible approach to using real-world data to measure rates of severe ALI following medication initiation among patients without liver or biliary disease…Patients initiating a medication with a high rate of severe ALI might require closer monitoring of liver-related laboratory tests to detect evolving hepatic dysfunction earlier, which might improve prognosis.”

The study illustrates the potential to use electronic health record data to “revolutionize how we characterize drug-related toxic effects,” not just on the liver but other organs, Grace Y. Zhang, MD, and Jessica B. Rubin, MD, MPH, of the University of California, San Francisco, wrote in an accompanying editorial. “If curated and disseminated effectively…such evidence will undoubtedly improve clinical decision-making and allow for more informed patient counseling regarding the true risks of starting or discontinuing medications.

SOURCE:

The study, led by Jessie Torgersen, MD, MHS, MSCE, of the Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, was published online in JAMA Internal Medicine.

LIMITATIONS:

The researchers listed several limitations, including the possibility that reliance on laboratory tests for ascertainment of acute liver injuries could introduce surveillance bias. The study focused on a population predominantly consisting of men without preexisting liver or biliary disease, so the findings may not be generalizable to women or individuals with liver disease. Additionally, researchers did not perform a causality assessment of all outcomes, did not study medications with fewer than four published case reports, and did not evaluate the influence of dosage.

DISCLOSURES:

This study was partly funded by several grants from the National Institutes of Health. Some authors declared receiving grants and personal fees from some of the funding agencies and other sources outside of this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.

Brazilian Peppertree Morphology and Geography

Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.¹ Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.²

Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.³ Since the 1840s,⁴ it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,⁵ Arizona,⁶ Nevada,³ and Texas.^5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,⁶ New Zealand,⁸ Australia, and various islands.⁹ The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.³

Identifying Features and Allergenic Plant Parts

Brazilian peppertree can be either a shrub or tree up to 30 feet tall.⁴ As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March⁷), bright red or pink (depending on the variety³) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.⁹ It characteristically exhibits 3 to 13 leaflets per leaf.¹⁰ The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin ­irritation (Figure 2B).⁶ Although the sap of the plant serves as the main culprit of Brazilian peppertree–­associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.^11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.⁶ Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.¹³

Urushiol, an oily resin present in most plants of the Anacardiaceae family,¹⁴ contains many chemicals, including allergenic phenols, catechols, and resorcinols.¹⁵ Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.⁶ Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.^11,12 In 1983, Stahl et al¹¹ identified a phenol, cardanol (chemical name ­3-pentadecylphenol¹⁶) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.¹¹ Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name ­5-pentadecylresorcinol),^15,16 though Stahl et al¹¹ were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,¹⁵ and these 2 substances are more irritating than cardanol.¹¹ A later study did identify cardol in addition to cardanol in Brazilian peppertree.¹²

Cutaneous Manifestations

Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.

Treatment

Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.¹⁷ Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.¹⁷

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.

Brazilian Peppertree Morphology and Geography

Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.¹ Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.²

Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.³ Since the 1840s,⁴ it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,⁵ Arizona,⁶ Nevada,³ and Texas.^5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,⁶ New Zealand,⁸ Australia, and various islands.⁹ The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.³

Identifying Features and Allergenic Plant Parts

Brazilian peppertree can be either a shrub or tree up to 30 feet tall.⁴ As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March⁷), bright red or pink (depending on the variety³) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.⁹ It characteristically exhibits 3 to 13 leaflets per leaf.¹⁰ The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin ­irritation (Figure 2B).⁶ Although the sap of the plant serves as the main culprit of Brazilian peppertree–­associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.^11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.⁶ Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.¹³

Urushiol, an oily resin present in most plants of the Anacardiaceae family,¹⁴ contains many chemicals, including allergenic phenols, catechols, and resorcinols.¹⁵ Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.⁶ Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.^11,12 In 1983, Stahl et al¹¹ identified a phenol, cardanol (chemical name ­3-pentadecylphenol¹⁶) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.¹¹ Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name ­5-pentadecylresorcinol),^15,16 though Stahl et al¹¹ were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,¹⁵ and these 2 substances are more irritating than cardanol.¹¹ A later study did identify cardol in addition to cardanol in Brazilian peppertree.¹²

Cutaneous Manifestations

Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.

Treatment

Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.¹⁷ Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.¹⁷

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, is an internationally invasive plant that causes allergic contact dermatitis (ACD) in susceptible individuals. This noxious weed has settled into the landscape of the southern United States and continues to expand. Its key identifying features include its year-round white flowers as well as a peppery and turpentinelike aroma created by cracking its bright red berries. The ACD associated with contact—primarily with the plant’s sap—stems from known alkenyl phenols, cardol and cardanol. Treatment of Brazilian peppertree–associated ACD parallels that for poison ivy. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree and its potential for harm.

Brazilian Peppertree Morphology and Geography

Plants in the Anacardiaceae family contribute to more ACD than any other family, and its 80 genera include most of the urushiol-containing plants, such as Toxicodendron (poison ivy, poison oak, poison sumac, Japanese lacquer tree), Anacardium (cashew tree), Mangifera (mango fruit), Semecarpus (India marking nut tree), and Schinus (Brazilian peppertree). Deciduous and evergreen tree members of the Anacardiaceae family grow primarily in tropical and subtropical locations and produce thick resins, 5-petalled flowers, and small fruit known as drupes. The genus name for Brazilian peppertree, Schinus, derives from Latin and Greek words meaning “mastic tree,” a relative of the pistachio tree that the Brazilian peppertree resembles.¹ Brazilian peppertree leaves look and smell similar to Pistacia terebinthus (turpentine tree or terebinth), from which the species name terebinthifolia derives.²

Brazilian peppertree originated in South America, particularly Brazil, Paraguay, and Argentina.³ Since the 1840s,⁴ it has been an invasive weed in the United States, notably in Florida, California, Hawaii, Alabama, Georgia,⁵ Arizona,⁶ Nevada,³ and Texas.^5,7 The plant also grows throughout the world, including parts of Africa, Asia, Central America, Europe,⁶ New Zealand,⁸ Australia, and various islands.⁹ The plant expertly outcompetes neighboring plants and has prompted control and eradication efforts in many locations.³

Identifying Features and Allergenic Plant Parts

Brazilian peppertree can be either a shrub or tree up to 30 feet tall.⁴ As an evergreen, it retains its leaves year-round. During fruiting seasons (primarily December through March⁷), bright red or pink (depending on the variety³) berries appear (Figure 1A) and contribute to its nickname “Florida holly.” Although generally considered an unwelcome guest in Florida, it does display white flowers (Figure 1B) year-round, especially from September to November.⁹ It characteristically exhibits 3 to 13 leaflets per leaf.¹⁰ The leaflets’ ovoid and ridged edges, netlike vasculature, shiny hue, and aroma can help identify the plant (Figure 2A). For decades, the sap of the Brazilian peppertree has been associated with skin ­irritation (Figure 2B).⁶ Although the sap of the plant serves as the main culprit of Brazilian peppertree–­associated ACD, it appears that other parts of the plant, including the fruit, can cause irritating effects to skin on contact.^11,12 The leaves, trunk, and fruit can be harmful to both humans and animals.⁶ Chemicals from flowers and crushed fruit also can lead to irritating effects in the respiratory tract if aspirated.¹³

Urushiol, an oily resin present in most plants of the Anacardiaceae family,¹⁴ contains many chemicals, including allergenic phenols, catechols, and resorcinols.¹⁵ Urushiol-allergic individuals develop dermatitis upon exposure to Brazilian peppertree sap.⁶ Alkenyl phenols found in Brazilian peppertree lead to the cutaneous manifestations in sensitized patients.^11,12 In 1983, Stahl et al¹¹ identified a phenol, cardanol (chemical name ­3-pentadecylphenol¹⁶) C15:1, in Brazilian peppertree fruit. The group further tested this compound’s effect on skin via patch testing, which showed an allergic response.¹¹ Cashew nut shells (Anacardium occidentale) contain cardanol, anacardic acid (a phenolic acid), and cardol (a phenol with the chemical name ­5-pentadecylresorcinol),^15,16 though Stahl et al¹¹ were unable to extract these 2 substances (if present) from Brazilian peppertree fruit. When exposed to cardol and anacardic acid, those allergic to poison ivy often develop ACD,¹⁵ and these 2 substances are more irritating than cardanol.¹¹ A later study did identify cardol in addition to cardanol in Brazilian peppertree.¹²

Cutaneous Manifestations

Brazilian peppertree–induced ACD appears similar to other plant-induced ACD with linear streaks of erythema, juicy papules, vesicles, coalescing erythematous plaques, and/or occasional edema and bullae accompanied by intense pruritus.

Treatment

Avoiding contact with Brazilian peppertree is the first line of defense, and treatment for a reaction associated with exposure is similar to that of poison ivy.¹⁷ Application of cool compresses, calamine lotion, and topical astringents offer symptom alleviation, and topical steroids (eg, clobetasol propionate 0.05% twice daily) can improve mild localized ACD when given prior to formation of blisters. For more severe and diffuse ACD, oral steroids (eg, prednisone 1 mg/kg/d tapered over 2–3 weeks) likely are necessary, though intramuscular options greatly alleviate discomfort in more severe cases (eg, intramuscular triamcinolone acetonide 1 mg/kg combined with betamethasone 0.1 mg/kg). Physicians should monitor sites for any signs of superimposed bacterial infection and initiate antibiotics as necessary.¹⁷