The U.S. Surgeon General says 13 years old is too young to begin using social media.

Most social media platforms including TikTok, Snapchat, Instagram, and Facebook allow users to create accounts if they say they are at least 13 years old.

“I, personally, based on the data I’ve seen, believe that 13 is too early. ... It’s a time where it’s really important for us to be thoughtful about what’s going into how they think about their own self-worth and their relationships, and the skewed and often distorted environment of social media often does a disservice to many of those children,” U.S. Surgeon General Vivek Murthy, MD, told CNN.

Research has shown that teens are susceptible to cyberbullying and serious mental health impacts from social media usage and online activity during an era when the influence of the Internet has become everywhere for young people.

According to the Pew Research Center, 95% of teens age 13 and up have a smartphone, and 97% of teens say they use the Internet daily. Among 13- and 14-year-olds, 61% say they use TikTok and 51% say they use Snapchat. Older teens ages 15-17 use those social media platforms at higher rates, with 71% saying they use TikTok and 65% using Snapchat.

“If parents can band together and say you know, as a group, we’re not going to allow our kids to use social media until 16 or 17 or 18 or whatever age they choose, that’s a much more effective strategy in making sure your kids don’t get exposed to harm early,” Dr. Murthy said.

A version of this article originally appeared on WebMD.com.

The U.S. Surgeon General says 13 years old is too young to begin using social media.

Most social media platforms including TikTok, Snapchat, Instagram, and Facebook allow users to create accounts if they say they are at least 13 years old.

“I, personally, based on the data I’ve seen, believe that 13 is too early. ... It’s a time where it’s really important for us to be thoughtful about what’s going into how they think about their own self-worth and their relationships, and the skewed and often distorted environment of social media often does a disservice to many of those children,” U.S. Surgeon General Vivek Murthy, MD, told CNN.

Research has shown that teens are susceptible to cyberbullying and serious mental health impacts from social media usage and online activity during an era when the influence of the Internet has become everywhere for young people.

According to the Pew Research Center, 95% of teens age 13 and up have a smartphone, and 97% of teens say they use the Internet daily. Among 13- and 14-year-olds, 61% say they use TikTok and 51% say they use Snapchat. Older teens ages 15-17 use those social media platforms at higher rates, with 71% saying they use TikTok and 65% using Snapchat.

“If parents can band together and say you know, as a group, we’re not going to allow our kids to use social media until 16 or 17 or 18 or whatever age they choose, that’s a much more effective strategy in making sure your kids don’t get exposed to harm early,” Dr. Murthy said.

A version of this article originally appeared on WebMD.com.

The U.S. Surgeon General says 13 years old is too young to begin using social media.

Most social media platforms including TikTok, Snapchat, Instagram, and Facebook allow users to create accounts if they say they are at least 13 years old.

“I, personally, based on the data I’ve seen, believe that 13 is too early. ... It’s a time where it’s really important for us to be thoughtful about what’s going into how they think about their own self-worth and their relationships, and the skewed and often distorted environment of social media often does a disservice to many of those children,” U.S. Surgeon General Vivek Murthy, MD, told CNN.

Research has shown that teens are susceptible to cyberbullying and serious mental health impacts from social media usage and online activity during an era when the influence of the Internet has become everywhere for young people.

According to the Pew Research Center, 95% of teens age 13 and up have a smartphone, and 97% of teens say they use the Internet daily. Among 13- and 14-year-olds, 61% say they use TikTok and 51% say they use Snapchat. Older teens ages 15-17 use those social media platforms at higher rates, with 71% saying they use TikTok and 65% using Snapchat.

“If parents can band together and say you know, as a group, we’re not going to allow our kids to use social media until 16 or 17 or 18 or whatever age they choose, that’s a much more effective strategy in making sure your kids don’t get exposed to harm early,” Dr. Murthy said.

A version of this article originally appeared on WebMD.com.

Montrouge, France – Whether you are a cisgender woman or a transgender man who has kept his uterus, regardless of the sex of your partner, and even if you are a woman who is no longer sexually active, you must take part in cervical cancer screening. This is the reminder issued by Julia Maruani, MD, a medical gynecologist in Marseille, France, at a press conference ahead of the 46th meeting of the French Colposcopy and Cervical-Vaginal Diseases Society (SFCPCV).

Cervical screening currently targets asymptomatic, immunocompetent, and sexually active women between ages 25 and 65 years. During her presentation, Dr. Maruani insisted that screening should not discriminate based on a patient’s sexual activity.
 

Sex between women

There is a widely held belief that only men can transmit human papillomavirus (HPV). “If you are in a sexual relationship with a man, then yes, you can get HPV from him. But it’s also possible for HPV to be transmitted in a sexual relationship between two women via touch, bodily fluids, or sex toys,” said Dr. Maruani, who pointed out that 20% of lesbians and 30% of bisexual women are HPV carriers.

Because women who have sexual relationships with other women have the mistaken view that their demographic is less affected, they are less likely to take part in cervical screening. They also present more often with advanced lesions and with cancer because of the lack of screening in this group.
 

Transgender men

Dr. Maruani defines transgender men as “women who have changed gender and who have become men.” Why are they affected by cervical screening? Not all of them are. Those who’ve had their uterus removed no longer have a cervix, so this screening doesn’t affect them. But hysterectomies are rarely performed, as they’re not required in most European countries to legally change gender.

The figures are concerning: 27% of transgender men are screened versus 60% of cisgender females.

“For this demographic, specialist gynecology appointments are hard to come by. Sitting in a women’s waiting room is not easy,” said Dr. Maruani, recalling that often discussion about the transition phase takes up the entire appointment time. It’s also usually the case that any medical problems or health care prevention issues not related to the topic of transitioning are not discussed.

Moreover, the online appointment-booking software doesn’t allow transgender men who have kept their cervix and legally identify as men to make an appointment. “Gynecologists must disable this default option,” said Dr. Maruani.

Likewise, transgender men will not receive an invitation to take part in cervical or breast cancer screening, as they are identified as male by social security services and screening sites. Furthermore, in what Dr. Maruani referred to as an “administrative head-scratcher that needs to change,” some medical procedures are not funded for men.

Yet the risk of contracting HPV is higher among transgender men than in the rest of the population because of different sexual practices in this demographic, as well as the propensity to have multiple sexual partners. The risk of finding abnormalities on cytology screening is greater.

Although data regarding cancer are lacking, “if screening is inadequate but the risk of infection with HPV is great, logic tells us that there will be more lesions, more cancer” in this demographic, said Dr. Maruani.
 

Celibate women

Nowadays, screening drops with age in women, especially after menopause. This is especially true for women who are no longer sexually active. Another preconceived notion to be addressed is that women who are no longer sexually active no longer need screening. But this concept completely goes against the natural history of HPV infection. “There are years, at least 5, between infection and the development of precancerous lesions. There is a further 5 years between a precancerous lesion and cancer,” said Dr. Maruani.

A woman could still be at risk even 20 years after contracting HPV. Approximately 80% of women are exposed to HPV, and 5%-10% have a persistent infection that could lead to the development of precancerous lesions.

“So, a woman who is no longer sexually active can’t stop participating in cervical screening, especially since there aren’t any symptoms until a fairly advanced stage of cancer.” No longer having sex does not mean that screening can be stopped.

What treatment is appropriate for partners of a woman who is no longer sexually active? None. During the press conference, the specialists agreed that a positive HPV test would be of importance to her partner. Even so, they recalled that the infection would generally be an old one and that the woman’s partner (whether male or female) would therefore have probably already been exposed to it. Patients should also be reminded that, in the past, cytology testing did not look for HPV, so the virus could already have been there. According to these specialists, you don’t need to change your sexual habits, just continue to monitor yourself.

This article was translated from the Medscape French edition and a version first appeared on Medscape.com.

Montrouge, France – Whether you are a cisgender woman or a transgender man who has kept his uterus, regardless of the sex of your partner, and even if you are a woman who is no longer sexually active, you must take part in cervical cancer screening. This is the reminder issued by Julia Maruani, MD, a medical gynecologist in Marseille, France, at a press conference ahead of the 46th meeting of the French Colposcopy and Cervical-Vaginal Diseases Society (SFCPCV).

Cervical screening currently targets asymptomatic, immunocompetent, and sexually active women between ages 25 and 65 years. During her presentation, Dr. Maruani insisted that screening should not discriminate based on a patient’s sexual activity.
 

Sex between women

There is a widely held belief that only men can transmit human papillomavirus (HPV). “If you are in a sexual relationship with a man, then yes, you can get HPV from him. But it’s also possible for HPV to be transmitted in a sexual relationship between two women via touch, bodily fluids, or sex toys,” said Dr. Maruani, who pointed out that 20% of lesbians and 30% of bisexual women are HPV carriers.

Because women who have sexual relationships with other women have the mistaken view that their demographic is less affected, they are less likely to take part in cervical screening. They also present more often with advanced lesions and with cancer because of the lack of screening in this group.
 

Transgender men

Dr. Maruani defines transgender men as “women who have changed gender and who have become men.” Why are they affected by cervical screening? Not all of them are. Those who’ve had their uterus removed no longer have a cervix, so this screening doesn’t affect them. But hysterectomies are rarely performed, as they’re not required in most European countries to legally change gender.

The figures are concerning: 27% of transgender men are screened versus 60% of cisgender females.

“For this demographic, specialist gynecology appointments are hard to come by. Sitting in a women’s waiting room is not easy,” said Dr. Maruani, recalling that often discussion about the transition phase takes up the entire appointment time. It’s also usually the case that any medical problems or health care prevention issues not related to the topic of transitioning are not discussed.

Moreover, the online appointment-booking software doesn’t allow transgender men who have kept their cervix and legally identify as men to make an appointment. “Gynecologists must disable this default option,” said Dr. Maruani.

Likewise, transgender men will not receive an invitation to take part in cervical or breast cancer screening, as they are identified as male by social security services and screening sites. Furthermore, in what Dr. Maruani referred to as an “administrative head-scratcher that needs to change,” some medical procedures are not funded for men.

Yet the risk of contracting HPV is higher among transgender men than in the rest of the population because of different sexual practices in this demographic, as well as the propensity to have multiple sexual partners. The risk of finding abnormalities on cytology screening is greater.

Although data regarding cancer are lacking, “if screening is inadequate but the risk of infection with HPV is great, logic tells us that there will be more lesions, more cancer” in this demographic, said Dr. Maruani.
 

Celibate women

Nowadays, screening drops with age in women, especially after menopause. This is especially true for women who are no longer sexually active. Another preconceived notion to be addressed is that women who are no longer sexually active no longer need screening. But this concept completely goes against the natural history of HPV infection. “There are years, at least 5, between infection and the development of precancerous lesions. There is a further 5 years between a precancerous lesion and cancer,” said Dr. Maruani.

A woman could still be at risk even 20 years after contracting HPV. Approximately 80% of women are exposed to HPV, and 5%-10% have a persistent infection that could lead to the development of precancerous lesions.

“So, a woman who is no longer sexually active can’t stop participating in cervical screening, especially since there aren’t any symptoms until a fairly advanced stage of cancer.” No longer having sex does not mean that screening can be stopped.

What treatment is appropriate for partners of a woman who is no longer sexually active? None. During the press conference, the specialists agreed that a positive HPV test would be of importance to her partner. Even so, they recalled that the infection would generally be an old one and that the woman’s partner (whether male or female) would therefore have probably already been exposed to it. Patients should also be reminded that, in the past, cytology testing did not look for HPV, so the virus could already have been there. According to these specialists, you don’t need to change your sexual habits, just continue to monitor yourself.

This article was translated from the Medscape French edition and a version first appeared on Medscape.com.

Montrouge, France – Whether you are a cisgender woman or a transgender man who has kept his uterus, regardless of the sex of your partner, and even if you are a woman who is no longer sexually active, you must take part in cervical cancer screening. This is the reminder issued by Julia Maruani, MD, a medical gynecologist in Marseille, France, at a press conference ahead of the 46th meeting of the French Colposcopy and Cervical-Vaginal Diseases Society (SFCPCV).

Cervical screening currently targets asymptomatic, immunocompetent, and sexually active women between ages 25 and 65 years. During her presentation, Dr. Maruani insisted that screening should not discriminate based on a patient’s sexual activity.
 

Sex between women

There is a widely held belief that only men can transmit human papillomavirus (HPV). “If you are in a sexual relationship with a man, then yes, you can get HPV from him. But it’s also possible for HPV to be transmitted in a sexual relationship between two women via touch, bodily fluids, or sex toys,” said Dr. Maruani, who pointed out that 20% of lesbians and 30% of bisexual women are HPV carriers.

Because women who have sexual relationships with other women have the mistaken view that their demographic is less affected, they are less likely to take part in cervical screening. They also present more often with advanced lesions and with cancer because of the lack of screening in this group.
 

Transgender men

Dr. Maruani defines transgender men as “women who have changed gender and who have become men.” Why are they affected by cervical screening? Not all of them are. Those who’ve had their uterus removed no longer have a cervix, so this screening doesn’t affect them. But hysterectomies are rarely performed, as they’re not required in most European countries to legally change gender.

The figures are concerning: 27% of transgender men are screened versus 60% of cisgender females.

“For this demographic, specialist gynecology appointments are hard to come by. Sitting in a women’s waiting room is not easy,” said Dr. Maruani, recalling that often discussion about the transition phase takes up the entire appointment time. It’s also usually the case that any medical problems or health care prevention issues not related to the topic of transitioning are not discussed.

Moreover, the online appointment-booking software doesn’t allow transgender men who have kept their cervix and legally identify as men to make an appointment. “Gynecologists must disable this default option,” said Dr. Maruani.

Likewise, transgender men will not receive an invitation to take part in cervical or breast cancer screening, as they are identified as male by social security services and screening sites. Furthermore, in what Dr. Maruani referred to as an “administrative head-scratcher that needs to change,” some medical procedures are not funded for men.

Yet the risk of contracting HPV is higher among transgender men than in the rest of the population because of different sexual practices in this demographic, as well as the propensity to have multiple sexual partners. The risk of finding abnormalities on cytology screening is greater.

Although data regarding cancer are lacking, “if screening is inadequate but the risk of infection with HPV is great, logic tells us that there will be more lesions, more cancer” in this demographic, said Dr. Maruani.
 

Celibate women

Nowadays, screening drops with age in women, especially after menopause. This is especially true for women who are no longer sexually active. Another preconceived notion to be addressed is that women who are no longer sexually active no longer need screening. But this concept completely goes against the natural history of HPV infection. “There are years, at least 5, between infection and the development of precancerous lesions. There is a further 5 years between a precancerous lesion and cancer,” said Dr. Maruani.

A woman could still be at risk even 20 years after contracting HPV. Approximately 80% of women are exposed to HPV, and 5%-10% have a persistent infection that could lead to the development of precancerous lesions.

“So, a woman who is no longer sexually active can’t stop participating in cervical screening, especially since there aren’t any symptoms until a fairly advanced stage of cancer.” No longer having sex does not mean that screening can be stopped.

What treatment is appropriate for partners of a woman who is no longer sexually active? None. During the press conference, the specialists agreed that a positive HPV test would be of importance to her partner. Even so, they recalled that the infection would generally be an old one and that the woman’s partner (whether male or female) would therefore have probably already been exposed to it. Patients should also be reminded that, in the past, cytology testing did not look for HPV, so the virus could already have been there. According to these specialists, you don’t need to change your sexual habits, just continue to monitor yourself.

This article was translated from the Medscape French edition and a version first appeared on Medscape.com.

The gyrate or cerebriform pattern of inflammatory, often pus-filled, subcutaneous tracts of the scalp pointed to a diagnosis of dissecting cellulitis. This patient did not have the fluctuant tracts frequently seen in more active disease but did have the scarring and alopecia common with this disorder.

Dissecting cellulitis is similar to acne and hidradenitis suppurativa in that it starts with follicular plugging. This plugging leads to inflammation, dilation and rupture of the follicle, and purulent sinus tract formation. The sinus tracts of the scalp can be extensive. Dissecting cellulitis is most common in 18- to 40-year-olds and more common in Black individuals.¹ When it occurs in conjunction with cystic acne and hidradenitis suppurativa, it is known as the follicular occlusion triad syndrome.

While oral antibiotics are an option for the treatment of dissecting cellulitis, oral isotretinoin is the first-line approach. Tumor necrosis factor alfa inhibitors have also been used with success, according to case reports.¹

Given that this patient had a small area of current inflammation, he was started on oral doxycycline 100 mg twice daily for 2 months. He was scheduled for a follow-up appointment in 3 months to reassess his progress and to explore treatment with isotretinoin if the condition worsened or did not improve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The gyrate or cerebriform pattern of inflammatory, often pus-filled, subcutaneous tracts of the scalp pointed to a diagnosis of dissecting cellulitis. This patient did not have the fluctuant tracts frequently seen in more active disease but did have the scarring and alopecia common with this disorder.

Dissecting cellulitis is similar to acne and hidradenitis suppurativa in that it starts with follicular plugging. This plugging leads to inflammation, dilation and rupture of the follicle, and purulent sinus tract formation. The sinus tracts of the scalp can be extensive. Dissecting cellulitis is most common in 18- to 40-year-olds and more common in Black individuals.¹ When it occurs in conjunction with cystic acne and hidradenitis suppurativa, it is known as the follicular occlusion triad syndrome.

While oral antibiotics are an option for the treatment of dissecting cellulitis, oral isotretinoin is the first-line approach. Tumor necrosis factor alfa inhibitors have also been used with success, according to case reports.¹

Given that this patient had a small area of current inflammation, he was started on oral doxycycline 100 mg twice daily for 2 months. He was scheduled for a follow-up appointment in 3 months to reassess his progress and to explore treatment with isotretinoin if the condition worsened or did not improve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The gyrate or cerebriform pattern of inflammatory, often pus-filled, subcutaneous tracts of the scalp pointed to a diagnosis of dissecting cellulitis. This patient did not have the fluctuant tracts frequently seen in more active disease but did have the scarring and alopecia common with this disorder.

Dissecting cellulitis is similar to acne and hidradenitis suppurativa in that it starts with follicular plugging. This plugging leads to inflammation, dilation and rupture of the follicle, and purulent sinus tract formation. The sinus tracts of the scalp can be extensive. Dissecting cellulitis is most common in 18- to 40-year-olds and more common in Black individuals.¹ When it occurs in conjunction with cystic acne and hidradenitis suppurativa, it is known as the follicular occlusion triad syndrome.

While oral antibiotics are an option for the treatment of dissecting cellulitis, oral isotretinoin is the first-line approach. Tumor necrosis factor alfa inhibitors have also been used with success, according to case reports.¹

Given that this patient had a small area of current inflammation, he was started on oral doxycycline 100 mg twice daily for 2 months. He was scheduled for a follow-up appointment in 3 months to reassess his progress and to explore treatment with isotretinoin if the condition worsened or did not improve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient’s targetoid and tingling skin lesions, in association with herpes simplex virus (HSV) infection, are a classic presentation of erythema multiforme (EM).

EM is an acute, self-limited, immune-mediated process that most commonly arises in a symmetrical pattern on acral surfaces. These lesions may be accompanied by eruptions on oral, anogenital, or ocular mucosa. EM is classified into 2 subtypes: major and minor. EM major refers to EM with significant mucosal involvement on at least 2 mucosal sites; it may also manifest with a prodrome of fevers, arthralgias, and malaise. EM minor is used to classify EM with minimal mucosal involvement.¹

The term “multiforme” denotes the varied dermatologic changes, including macules, papules, and targetoid lesions with 3 identifiable zones, which are pathognomonic for EM. The classic 3 zones consist of an inner dusky, vesicular, or necrotic center; a middle elevated edematous surrounding ring; and an outer ring of macular erythema. Patients may also present with an atypical macular target lesion, characterized by fewer than 3 zones with an ill-defined border between the zones. The lesions may be asymptomatic, or patients may describe an itchy or burning sensation.

The differential diagnosis of EM includes urticaria, fixed drug eruption, subacute lupus erythematosus, Kawasaki disease, erythema annulare centrifugum, vasculitis, and Stevens-Johnson syndrome.

Infections with HSV types 1 or 2 are the leading cause of EM and are thought to involve a cell-mediated immune process directed against viral antigens in skin.² Other infectious causes include cytomegalovirus, Epstein-Barr virus, influenza virus, and—rarely—newer strains of coronavirus.³ Pharmacologic reactions are the cause in a small percentage of patients, and may involve nonsteroidal anti-inflammatory drugs, antibiotics, sulfonamides, antiepileptics, and tumor necrosis factor-alpha inhibitors. Studies also link the development of EM to primary malignancy, autoimmune disease, and immunizations.¹

The treatment of EM is dependent on the clinical course and severity of the disease. If a causative agent is identified, it should be discontinued (if a drug) or treated (if an infection). Topical antiseptic mouthwashes, antihistamines, and topical corticosteroids can be used to relieve cutaneous discomfort. Biologics and immunosuppressants can be used with patients who have severe symptoms or functional impairment. Patients who have recurrences associated with HSV should be given antiviral prophylaxis for 6 months consisting of oral acyclovir 10 mg/kg/d, valacyclovir 500 to 1000 mg/d, or famciclovir 250 mg twice daily.¹

Given the recurrent nature of this patient’s disease, and its association with HSV outbreaks, he was prescribed prophylactic valacyclovir 1000 mg/d orally for 6 months to reduce HSV outbreaks and hopefully prevent future EM episodes.

‌

Photo courtesy of Cyrelle F. Finan, MD. Text courtesy of Lynn Midani, BS, University of New Mexico School of Medicine, and Cyrelle F. Finan, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient’s targetoid and tingling skin lesions, in association with herpes simplex virus (HSV) infection, are a classic presentation of erythema multiforme (EM).

EM is an acute, self-limited, immune-mediated process that most commonly arises in a symmetrical pattern on acral surfaces. These lesions may be accompanied by eruptions on oral, anogenital, or ocular mucosa. EM is classified into 2 subtypes: major and minor. EM major refers to EM with significant mucosal involvement on at least 2 mucosal sites; it may also manifest with a prodrome of fevers, arthralgias, and malaise. EM minor is used to classify EM with minimal mucosal involvement.¹

The term “multiforme” denotes the varied dermatologic changes, including macules, papules, and targetoid lesions with 3 identifiable zones, which are pathognomonic for EM. The classic 3 zones consist of an inner dusky, vesicular, or necrotic center; a middle elevated edematous surrounding ring; and an outer ring of macular erythema. Patients may also present with an atypical macular target lesion, characterized by fewer than 3 zones with an ill-defined border between the zones. The lesions may be asymptomatic, or patients may describe an itchy or burning sensation.

The differential diagnosis of EM includes urticaria, fixed drug eruption, subacute lupus erythematosus, Kawasaki disease, erythema annulare centrifugum, vasculitis, and Stevens-Johnson syndrome.

Infections with HSV types 1 or 2 are the leading cause of EM and are thought to involve a cell-mediated immune process directed against viral antigens in skin.² Other infectious causes include cytomegalovirus, Epstein-Barr virus, influenza virus, and—rarely—newer strains of coronavirus.³ Pharmacologic reactions are the cause in a small percentage of patients, and may involve nonsteroidal anti-inflammatory drugs, antibiotics, sulfonamides, antiepileptics, and tumor necrosis factor-alpha inhibitors. Studies also link the development of EM to primary malignancy, autoimmune disease, and immunizations.¹

The treatment of EM is dependent on the clinical course and severity of the disease. If a causative agent is identified, it should be discontinued (if a drug) or treated (if an infection). Topical antiseptic mouthwashes, antihistamines, and topical corticosteroids can be used to relieve cutaneous discomfort. Biologics and immunosuppressants can be used with patients who have severe symptoms or functional impairment. Patients who have recurrences associated with HSV should be given antiviral prophylaxis for 6 months consisting of oral acyclovir 10 mg/kg/d, valacyclovir 500 to 1000 mg/d, or famciclovir 250 mg twice daily.¹

Given the recurrent nature of this patient’s disease, and its association with HSV outbreaks, he was prescribed prophylactic valacyclovir 1000 mg/d orally for 6 months to reduce HSV outbreaks and hopefully prevent future EM episodes.

‌

Photo courtesy of Cyrelle F. Finan, MD. Text courtesy of Lynn Midani, BS, University of New Mexico School of Medicine, and Cyrelle F. Finan, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This patient’s targetoid and tingling skin lesions, in association with herpes simplex virus (HSV) infection, are a classic presentation of erythema multiforme (EM).

EM is an acute, self-limited, immune-mediated process that most commonly arises in a symmetrical pattern on acral surfaces. These lesions may be accompanied by eruptions on oral, anogenital, or ocular mucosa. EM is classified into 2 subtypes: major and minor. EM major refers to EM with significant mucosal involvement on at least 2 mucosal sites; it may also manifest with a prodrome of fevers, arthralgias, and malaise. EM minor is used to classify EM with minimal mucosal involvement.¹

The term “multiforme” denotes the varied dermatologic changes, including macules, papules, and targetoid lesions with 3 identifiable zones, which are pathognomonic for EM. The classic 3 zones consist of an inner dusky, vesicular, or necrotic center; a middle elevated edematous surrounding ring; and an outer ring of macular erythema. Patients may also present with an atypical macular target lesion, characterized by fewer than 3 zones with an ill-defined border between the zones. The lesions may be asymptomatic, or patients may describe an itchy or burning sensation.

The differential diagnosis of EM includes urticaria, fixed drug eruption, subacute lupus erythematosus, Kawasaki disease, erythema annulare centrifugum, vasculitis, and Stevens-Johnson syndrome.

Infections with HSV types 1 or 2 are the leading cause of EM and are thought to involve a cell-mediated immune process directed against viral antigens in skin.² Other infectious causes include cytomegalovirus, Epstein-Barr virus, influenza virus, and—rarely—newer strains of coronavirus.³ Pharmacologic reactions are the cause in a small percentage of patients, and may involve nonsteroidal anti-inflammatory drugs, antibiotics, sulfonamides, antiepileptics, and tumor necrosis factor-alpha inhibitors. Studies also link the development of EM to primary malignancy, autoimmune disease, and immunizations.¹

The treatment of EM is dependent on the clinical course and severity of the disease. If a causative agent is identified, it should be discontinued (if a drug) or treated (if an infection). Topical antiseptic mouthwashes, antihistamines, and topical corticosteroids can be used to relieve cutaneous discomfort. Biologics and immunosuppressants can be used with patients who have severe symptoms or functional impairment. Patients who have recurrences associated with HSV should be given antiviral prophylaxis for 6 months consisting of oral acyclovir 10 mg/kg/d, valacyclovir 500 to 1000 mg/d, or famciclovir 250 mg twice daily.¹

Given the recurrent nature of this patient’s disease, and its association with HSV outbreaks, he was prescribed prophylactic valacyclovir 1000 mg/d orally for 6 months to reduce HSV outbreaks and hopefully prevent future EM episodes.

‌

Photo courtesy of Cyrelle F. Finan, MD. Text courtesy of Lynn Midani, BS, University of New Mexico School of Medicine, and Cyrelle F. Finan, MD, Department of Dermatology, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

The Diagnosis: Annular Elastolytic Giant Cell Granuloma

Histologic examination of the shave biopsies showed a granulomatous infiltrate of small lymphocytes, histiocytes, and multinucleated giant cells. The giant cells have abundant eosinophilic cytoplasm, with several also containing fragments of basophilic elastic fibers (elastophagocytosis)(Figure). Additionally, the granulomas revealed no signs of necrosis, making an infectious source unlikely, and examination under polarized light was negative for foreign material. These clinical and histologic findings were diagnostic for annular elastolytic giant cell granuloma (AEGCG).

Annular elastolytic giant cell granuloma is a rare chronic inflammatory disorder that classically presents on sun-exposed skin as annular plaques with elevated borders and atrophic centers.^1-4 Histologically, AEGCG is characterized by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes, and lymphocytes in the dermis, along with phagocytosis of elastic fibers by multinucleated giant cells.⁵ The underlying etiology and pathogenesis of AEGCG remains unknown.⁶

Annular elastolytic giant cell granuloma commonly affects females aged 35 to 75 years; however, cases have been reported in the male and pediatric patient populations.^1,2 Documented cases are known to last from 1 month to 10 years.^7,8 Although the mechanisms underlying the development of AEGCG remain to be elucidated, studies have determined that the skin disorder is associated with sarcoidosis, molluscum contagiosum, amyloidosis, diabetes mellitus, and cutaneous T-cell lymphoma.⁹ Diabetes mellitus is the most common comorbidity associated with AEGCG, and it is theorized that diabetes contributes to the increased incidence of AEGCG in this population by inducing damage to elastic fibers in the skin.¹⁰ One study that examined 50 cases of AEGCG found that 38 patients had serum glucose levels evaluated, with 8 cases being subsequently diagnosed with diabetes mellitus and 6 cases with apparent impaired glucose tolerance, indicating that 37% of the sample population with AEGCG who were evaluated for metabolic disease were found to have definitive or latent type 2 diabetes mellitus.¹¹ Although AEGCG is a rare disorder, a substantial number of patients diagnosed with AEGCG also have diabetes mellitus, making it important to consider screening all patients with AEGCG for diabetes given the ease and widely available resources to check glucose levels.

Actinic granuloma, granuloma annulare, atypical facial necrobiosis lipoidica, granuloma multiforme, secondary syphilis, tinea corporis, and erythema annulare centrifugum most commonly are included in the differential diagnosis with AEGCG; histopathology is the key determinant in discerning between these conditions.¹² Our patient presented with typical annular plaques overlying hyperpigmented telangiectatic patches. With known type 2 diabetes mellitus and the clinical findings, granuloma annulare, erythema annulare centrifugum, and AEGCG remained high on the differential.

No standard of care exists for AEGCG due to its rare nature and tendency to spontaneously resolve. The most common first-line treatment includes topical and intralesional steroids, topical pimecrolimus, and the use of sunscreen and other sun-protective measures. UV radiation, specifically UVA, has been determined to be a causal factor for AEGCG by changing the antigenicity of elastic fibers and producing an immune response in individuals with fair skin.¹³ Further, resistant cases of AEGCG successfully have been treated with cyclosporine, systemic steroids, antimalarials, dapsone, and oral retinoids.^14,15 Some studies reported partial regression or full resolution with topical tretinoin; adalimumab; clobetasol ointment; or a combination of corticosteroids, antihistamines, and hydroxychloroquine.² Only 1 case series using sulfasalazine reported worsening symptoms after treatment initiation.¹⁶ Our patient deferred systemic medications and was treated with 4 weeks of topical triamcinolone followed by 4 weeks of topical tacrolimus with minimal improvement. At the time of diagnosis, our patient also was encouraged to use sun-protective measures. At 6-month follow-up, the lesions remained stable, and the decision was made to continue with photoprotection.

The Diagnosis: Annular Elastolytic Giant Cell Granuloma

Histologic examination of the shave biopsies showed a granulomatous infiltrate of small lymphocytes, histiocytes, and multinucleated giant cells. The giant cells have abundant eosinophilic cytoplasm, with several also containing fragments of basophilic elastic fibers (elastophagocytosis)(Figure). Additionally, the granulomas revealed no signs of necrosis, making an infectious source unlikely, and examination under polarized light was negative for foreign material. These clinical and histologic findings were diagnostic for annular elastolytic giant cell granuloma (AEGCG).

Annular elastolytic giant cell granuloma is a rare chronic inflammatory disorder that classically presents on sun-exposed skin as annular plaques with elevated borders and atrophic centers.^1-4 Histologically, AEGCG is characterized by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes, and lymphocytes in the dermis, along with phagocytosis of elastic fibers by multinucleated giant cells.⁵ The underlying etiology and pathogenesis of AEGCG remains unknown.⁶

Annular elastolytic giant cell granuloma commonly affects females aged 35 to 75 years; however, cases have been reported in the male and pediatric patient populations.^1,2 Documented cases are known to last from 1 month to 10 years.^7,8 Although the mechanisms underlying the development of AEGCG remain to be elucidated, studies have determined that the skin disorder is associated with sarcoidosis, molluscum contagiosum, amyloidosis, diabetes mellitus, and cutaneous T-cell lymphoma.⁹ Diabetes mellitus is the most common comorbidity associated with AEGCG, and it is theorized that diabetes contributes to the increased incidence of AEGCG in this population by inducing damage to elastic fibers in the skin.¹⁰ One study that examined 50 cases of AEGCG found that 38 patients had serum glucose levels evaluated, with 8 cases being subsequently diagnosed with diabetes mellitus and 6 cases with apparent impaired glucose tolerance, indicating that 37% of the sample population with AEGCG who were evaluated for metabolic disease were found to have definitive or latent type 2 diabetes mellitus.¹¹ Although AEGCG is a rare disorder, a substantial number of patients diagnosed with AEGCG also have diabetes mellitus, making it important to consider screening all patients with AEGCG for diabetes given the ease and widely available resources to check glucose levels.

Actinic granuloma, granuloma annulare, atypical facial necrobiosis lipoidica, granuloma multiforme, secondary syphilis, tinea corporis, and erythema annulare centrifugum most commonly are included in the differential diagnosis with AEGCG; histopathology is the key determinant in discerning between these conditions.¹² Our patient presented with typical annular plaques overlying hyperpigmented telangiectatic patches. With known type 2 diabetes mellitus and the clinical findings, granuloma annulare, erythema annulare centrifugum, and AEGCG remained high on the differential.

No standard of care exists for AEGCG due to its rare nature and tendency to spontaneously resolve. The most common first-line treatment includes topical and intralesional steroids, topical pimecrolimus, and the use of sunscreen and other sun-protective measures. UV radiation, specifically UVA, has been determined to be a causal factor for AEGCG by changing the antigenicity of elastic fibers and producing an immune response in individuals with fair skin.¹³ Further, resistant cases of AEGCG successfully have been treated with cyclosporine, systemic steroids, antimalarials, dapsone, and oral retinoids.^14,15 Some studies reported partial regression or full resolution with topical tretinoin; adalimumab; clobetasol ointment; or a combination of corticosteroids, antihistamines, and hydroxychloroquine.² Only 1 case series using sulfasalazine reported worsening symptoms after treatment initiation.¹⁶ Our patient deferred systemic medications and was treated with 4 weeks of topical triamcinolone followed by 4 weeks of topical tacrolimus with minimal improvement. At the time of diagnosis, our patient also was encouraged to use sun-protective measures. At 6-month follow-up, the lesions remained stable, and the decision was made to continue with photoprotection.

The Diagnosis: Annular Elastolytic Giant Cell Granuloma

Histologic examination of the shave biopsies showed a granulomatous infiltrate of small lymphocytes, histiocytes, and multinucleated giant cells. The giant cells have abundant eosinophilic cytoplasm, with several also containing fragments of basophilic elastic fibers (elastophagocytosis)(Figure). Additionally, the granulomas revealed no signs of necrosis, making an infectious source unlikely, and examination under polarized light was negative for foreign material. These clinical and histologic findings were diagnostic for annular elastolytic giant cell granuloma (AEGCG).

Annular elastolytic giant cell granuloma is a rare chronic inflammatory disorder that classically presents on sun-exposed skin as annular plaques with elevated borders and atrophic centers.^1-4 Histologically, AEGCG is characterized by diffuse granulomatous infiltrates composed of multinucleated giant cells, histiocytes, and lymphocytes in the dermis, along with phagocytosis of elastic fibers by multinucleated giant cells.⁵ The underlying etiology and pathogenesis of AEGCG remains unknown.⁶

Annular elastolytic giant cell granuloma commonly affects females aged 35 to 75 years; however, cases have been reported in the male and pediatric patient populations.^1,2 Documented cases are known to last from 1 month to 10 years.^7,8 Although the mechanisms underlying the development of AEGCG remain to be elucidated, studies have determined that the skin disorder is associated with sarcoidosis, molluscum contagiosum, amyloidosis, diabetes mellitus, and cutaneous T-cell lymphoma.⁹ Diabetes mellitus is the most common comorbidity associated with AEGCG, and it is theorized that diabetes contributes to the increased incidence of AEGCG in this population by inducing damage to elastic fibers in the skin.¹⁰ One study that examined 50 cases of AEGCG found that 38 patients had serum glucose levels evaluated, with 8 cases being subsequently diagnosed with diabetes mellitus and 6 cases with apparent impaired glucose tolerance, indicating that 37% of the sample population with AEGCG who were evaluated for metabolic disease were found to have definitive or latent type 2 diabetes mellitus.¹¹ Although AEGCG is a rare disorder, a substantial number of patients diagnosed with AEGCG also have diabetes mellitus, making it important to consider screening all patients with AEGCG for diabetes given the ease and widely available resources to check glucose levels.

Actinic granuloma, granuloma annulare, atypical facial necrobiosis lipoidica, granuloma multiforme, secondary syphilis, tinea corporis, and erythema annulare centrifugum most commonly are included in the differential diagnosis with AEGCG; histopathology is the key determinant in discerning between these conditions.¹² Our patient presented with typical annular plaques overlying hyperpigmented telangiectatic patches. With known type 2 diabetes mellitus and the clinical findings, granuloma annulare, erythema annulare centrifugum, and AEGCG remained high on the differential.

No standard of care exists for AEGCG due to its rare nature and tendency to spontaneously resolve. The most common first-line treatment includes topical and intralesional steroids, topical pimecrolimus, and the use of sunscreen and other sun-protective measures. UV radiation, specifically UVA, has been determined to be a causal factor for AEGCG by changing the antigenicity of elastic fibers and producing an immune response in individuals with fair skin.¹³ Further, resistant cases of AEGCG successfully have been treated with cyclosporine, systemic steroids, antimalarials, dapsone, and oral retinoids.^14,15 Some studies reported partial regression or full resolution with topical tretinoin; adalimumab; clobetasol ointment; or a combination of corticosteroids, antihistamines, and hydroxychloroquine.² Only 1 case series using sulfasalazine reported worsening symptoms after treatment initiation.¹⁶ Our patient deferred systemic medications and was treated with 4 weeks of topical triamcinolone followed by 4 weeks of topical tacrolimus with minimal improvement. At the time of diagnosis, our patient also was encouraged to use sun-protective measures. At 6-month follow-up, the lesions remained stable, and the decision was made to continue with photoprotection.

A Mendelian randomization study employing data from nearly 300,000 individuals has linked elevated levels of the PCSK9 enzyme with an increased risk of psoriasis, suggesting it might be targetable as an intervention.

Independent of low-density lipoprotein cholesterol (LDL-C), which is reduced when PCSK9 is inhibited, a reduction in PCSK9 levels appears to have a direct impact on lowering psoriasis risk. Conversely, psoriasis risk did not appear to be affected when LDL-C was reduced by other pathways of lipid control.

petekarici/Getty Images

This study “suggests that PCSK9 inhibition is causally associated with reduced risk of psoriasis,” reported a team of investigators led by Sizheng Steven Zhao, MD, PhD, of the division of musculoskeletal and dermatological sciences, University of Manchester (England). “Existing PCSK9 inhibitors hold potential as therapeutic targets for prevention, and possibly treatment, of psoriasis, although further clinical studies are needed,” they concluded.

In an interview, Dr. Zhao also noted that it will be interesting to look at psoriasis susceptibility in post hoc analyses of large randomized controlled trials of PCSK9 inhibitors for cardiovascular disease.

“Genetically proxied” inhibition of HMG-CoA reductase, which is targeted by statins, and NPC1L1 which is targeted by ezetimibe, “were not associated with psoriasis risk,” the investigators reported in the study, published in JAMA Dermatology.

Abnormal lipid metabolism is sufficiently common among people with psoriasis that screening in patients with moderate to severe disease is recommended in 2019 psoriasis guidelines from the American Academy of Dermatology and the National Psoriasis Foundation. However, the link between these diseases is unclear. This study was launched to explore genetically proxied relationships between psoriasis and LDL-C reductions as well as specific treatments for elevated LDL-C.

Mendelian randomizations were applied to deidentified data from two sources, a UK biobank and FinnGen, a Finnish-based project for identifying genotype-to-phenotype correlations. Genetic proxies for these variables were established on the basis of genomewide association studies on large population samples.

Ultimately, 34 genetic variants were selected to proxy for lipid lowering by PCSK9, 19 were selected to proxy for HMG-CoA reductase, and 9 for NPC1L1. In the Mendelian analyses performed on the two sources, genetically proxied PCSK9 inhibition was associated with about a 30% reduction in the odds ratio of psoriasis (OR, 0.69; P = .003). There were no robust associations with proxies for reductions in either HMG-CoA reductase or NPC1L1.

In sensitivity analyses, there was no evidence of bias from pleiotropy or genetic confounding, according to Dr. Zhao and his coauthors, who noted that the relationship between reductions in PCSK9 and reduced risk of psoriasis appeared to be independent of change in circulating LDL-C.

Given the prior evidence implicating the PCSK9 enzyme in psoriasis risk, “this is an exciting study that really highlights the importance of studying and targeting lipid metabolism in psoriasis for a few reasons,” according to Michael S. Garshick, MD, a researcher, cardiologist, and director of the cardio-rheumatology program, New York University Langone Health.

An investigator who has participated in several studies evaluating the relationship between cardiovascular risk and psoriasis, Dr. Garshick said there is increasing interest in PCSK9 as a biomarker or even a mediator of inflammation independent of blood lipid levels.

“In psoriasis regarding PCSK9, we and others have shown PCSK9 is elevated in psoriatic lesion skin, and studies are starting to investigate the unique lipidomic profile in psoriasis,” Dr. Garshick said in an interview. The study he led that showed elevated PCSK9 levels in psoriatic skin was published in 2021 in the Journal of Investigative Dermatology.

While the Mendelian randomization provides only “an inference” that PCSK9 plays a role in mediating risk of psoriasis, Dr. Zhao and coauthors cited numerous studies linking elevated PCSK9 to psoriasis pathophysiology. This not only includes the elevated PCSK9 expression in psoriatic plaques as shown by Dr. Garshick and others but several sets of experimental evidence linking PCSK9 to inflammatory pathways, including upregulation of interleukin-17 and stimulation of macrophage activation.

While Dr. Zhao and coauthors suggested that clinical trials are now needed to test the potential of PCSK9 inhibitors to modify the risk of psoriasis, Dr. Garshick indicated that there are numerous variables to unravel in the relationship between elevated lipids, PCSK9, and psoriasis.

“In our own studies, we did see a statistical correlation between circulating PCSK9 and psoriasis severity,” Dr. Garshick said. But he added, “I think we are just beginning to understand the functions of circulating (extrahepatic) PCSK9 independent of lipid metabolism.”

While he is intrigued by the evidence that PCSK9 is linked to systemic inflammation, he pointed out that several medications used to treat dyslipidemias, such as statins, are associated with an anti-inflammatory effect.

This study “further emphasizes the need to conduct clinical trials treating dyslipidemia in psoriasis, including the targeting of PCSK9, whether it is with statins with lipid lowering and potential pleiotropic anti-inflammatory properties or PCSK9 inhibition,” he said. If positive, “both would be exciting.“

From a cardiologist’s point of view, there is an upside for including patients with psoriasis in lipid-lowering trials even if the effect on psoriasis is modest. Either way, “you still get the lipid-lowering benefit, which is important for reducing atherosclerotic cardiovascular disease,” Dr. Garshick said.

Dr. Zhao reported financial relationships with UCB, although UCB did not provide funding for this study. One author reported grants from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre during the study, grants from Bristol Myers Squibb, Galapagos, and Pfizer, and personal fees from Chugai Roche outside the submitted work. No other disclosures were reported. The study was supported by grants from Versus Arthritis and the NIHR Manchester Biomedical Research Centre. Dr. Garshick reported financial relationships with AbbVie and Horizon Therapeutics.

A Mendelian randomization study employing data from nearly 300,000 individuals has linked elevated levels of the PCSK9 enzyme with an increased risk of psoriasis, suggesting it might be targetable as an intervention.

Independent of low-density lipoprotein cholesterol (LDL-C), which is reduced when PCSK9 is inhibited, a reduction in PCSK9 levels appears to have a direct impact on lowering psoriasis risk. Conversely, psoriasis risk did not appear to be affected when LDL-C was reduced by other pathways of lipid control.

petekarici/Getty Images

This study “suggests that PCSK9 inhibition is causally associated with reduced risk of psoriasis,” reported a team of investigators led by Sizheng Steven Zhao, MD, PhD, of the division of musculoskeletal and dermatological sciences, University of Manchester (England). “Existing PCSK9 inhibitors hold potential as therapeutic targets for prevention, and possibly treatment, of psoriasis, although further clinical studies are needed,” they concluded.

In an interview, Dr. Zhao also noted that it will be interesting to look at psoriasis susceptibility in post hoc analyses of large randomized controlled trials of PCSK9 inhibitors for cardiovascular disease.

“Genetically proxied” inhibition of HMG-CoA reductase, which is targeted by statins, and NPC1L1 which is targeted by ezetimibe, “were not associated with psoriasis risk,” the investigators reported in the study, published in JAMA Dermatology.

Abnormal lipid metabolism is sufficiently common among people with psoriasis that screening in patients with moderate to severe disease is recommended in 2019 psoriasis guidelines from the American Academy of Dermatology and the National Psoriasis Foundation. However, the link between these diseases is unclear. This study was launched to explore genetically proxied relationships between psoriasis and LDL-C reductions as well as specific treatments for elevated LDL-C.

Mendelian randomizations were applied to deidentified data from two sources, a UK biobank and FinnGen, a Finnish-based project for identifying genotype-to-phenotype correlations. Genetic proxies for these variables were established on the basis of genomewide association studies on large population samples.

Ultimately, 34 genetic variants were selected to proxy for lipid lowering by PCSK9, 19 were selected to proxy for HMG-CoA reductase, and 9 for NPC1L1. In the Mendelian analyses performed on the two sources, genetically proxied PCSK9 inhibition was associated with about a 30% reduction in the odds ratio of psoriasis (OR, 0.69; P = .003). There were no robust associations with proxies for reductions in either HMG-CoA reductase or NPC1L1.

In sensitivity analyses, there was no evidence of bias from pleiotropy or genetic confounding, according to Dr. Zhao and his coauthors, who noted that the relationship between reductions in PCSK9 and reduced risk of psoriasis appeared to be independent of change in circulating LDL-C.

Given the prior evidence implicating the PCSK9 enzyme in psoriasis risk, “this is an exciting study that really highlights the importance of studying and targeting lipid metabolism in psoriasis for a few reasons,” according to Michael S. Garshick, MD, a researcher, cardiologist, and director of the cardio-rheumatology program, New York University Langone Health.

An investigator who has participated in several studies evaluating the relationship between cardiovascular risk and psoriasis, Dr. Garshick said there is increasing interest in PCSK9 as a biomarker or even a mediator of inflammation independent of blood lipid levels.

“In psoriasis regarding PCSK9, we and others have shown PCSK9 is elevated in psoriatic lesion skin, and studies are starting to investigate the unique lipidomic profile in psoriasis,” Dr. Garshick said in an interview. The study he led that showed elevated PCSK9 levels in psoriatic skin was published in 2021 in the Journal of Investigative Dermatology.

While the Mendelian randomization provides only “an inference” that PCSK9 plays a role in mediating risk of psoriasis, Dr. Zhao and coauthors cited numerous studies linking elevated PCSK9 to psoriasis pathophysiology. This not only includes the elevated PCSK9 expression in psoriatic plaques as shown by Dr. Garshick and others but several sets of experimental evidence linking PCSK9 to inflammatory pathways, including upregulation of interleukin-17 and stimulation of macrophage activation.

While Dr. Zhao and coauthors suggested that clinical trials are now needed to test the potential of PCSK9 inhibitors to modify the risk of psoriasis, Dr. Garshick indicated that there are numerous variables to unravel in the relationship between elevated lipids, PCSK9, and psoriasis.

“In our own studies, we did see a statistical correlation between circulating PCSK9 and psoriasis severity,” Dr. Garshick said. But he added, “I think we are just beginning to understand the functions of circulating (extrahepatic) PCSK9 independent of lipid metabolism.”

While he is intrigued by the evidence that PCSK9 is linked to systemic inflammation, he pointed out that several medications used to treat dyslipidemias, such as statins, are associated with an anti-inflammatory effect.

This study “further emphasizes the need to conduct clinical trials treating dyslipidemia in psoriasis, including the targeting of PCSK9, whether it is with statins with lipid lowering and potential pleiotropic anti-inflammatory properties or PCSK9 inhibition,” he said. If positive, “both would be exciting.“

From a cardiologist’s point of view, there is an upside for including patients with psoriasis in lipid-lowering trials even if the effect on psoriasis is modest. Either way, “you still get the lipid-lowering benefit, which is important for reducing atherosclerotic cardiovascular disease,” Dr. Garshick said.

Dr. Zhao reported financial relationships with UCB, although UCB did not provide funding for this study. One author reported grants from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre during the study, grants from Bristol Myers Squibb, Galapagos, and Pfizer, and personal fees from Chugai Roche outside the submitted work. No other disclosures were reported. The study was supported by grants from Versus Arthritis and the NIHR Manchester Biomedical Research Centre. Dr. Garshick reported financial relationships with AbbVie and Horizon Therapeutics.

A Mendelian randomization study employing data from nearly 300,000 individuals has linked elevated levels of the PCSK9 enzyme with an increased risk of psoriasis, suggesting it might be targetable as an intervention.

Independent of low-density lipoprotein cholesterol (LDL-C), which is reduced when PCSK9 is inhibited, a reduction in PCSK9 levels appears to have a direct impact on lowering psoriasis risk. Conversely, psoriasis risk did not appear to be affected when LDL-C was reduced by other pathways of lipid control.

petekarici/Getty Images

This study “suggests that PCSK9 inhibition is causally associated with reduced risk of psoriasis,” reported a team of investigators led by Sizheng Steven Zhao, MD, PhD, of the division of musculoskeletal and dermatological sciences, University of Manchester (England). “Existing PCSK9 inhibitors hold potential as therapeutic targets for prevention, and possibly treatment, of psoriasis, although further clinical studies are needed,” they concluded.

In an interview, Dr. Zhao also noted that it will be interesting to look at psoriasis susceptibility in post hoc analyses of large randomized controlled trials of PCSK9 inhibitors for cardiovascular disease.

“Genetically proxied” inhibition of HMG-CoA reductase, which is targeted by statins, and NPC1L1 which is targeted by ezetimibe, “were not associated with psoriasis risk,” the investigators reported in the study, published in JAMA Dermatology.

Abnormal lipid metabolism is sufficiently common among people with psoriasis that screening in patients with moderate to severe disease is recommended in 2019 psoriasis guidelines from the American Academy of Dermatology and the National Psoriasis Foundation. However, the link between these diseases is unclear. This study was launched to explore genetically proxied relationships between psoriasis and LDL-C reductions as well as specific treatments for elevated LDL-C.

Mendelian randomizations were applied to deidentified data from two sources, a UK biobank and FinnGen, a Finnish-based project for identifying genotype-to-phenotype correlations. Genetic proxies for these variables were established on the basis of genomewide association studies on large population samples.

Ultimately, 34 genetic variants were selected to proxy for lipid lowering by PCSK9, 19 were selected to proxy for HMG-CoA reductase, and 9 for NPC1L1. In the Mendelian analyses performed on the two sources, genetically proxied PCSK9 inhibition was associated with about a 30% reduction in the odds ratio of psoriasis (OR, 0.69; P = .003). There were no robust associations with proxies for reductions in either HMG-CoA reductase or NPC1L1.

In sensitivity analyses, there was no evidence of bias from pleiotropy or genetic confounding, according to Dr. Zhao and his coauthors, who noted that the relationship between reductions in PCSK9 and reduced risk of psoriasis appeared to be independent of change in circulating LDL-C.

Given the prior evidence implicating the PCSK9 enzyme in psoriasis risk, “this is an exciting study that really highlights the importance of studying and targeting lipid metabolism in psoriasis for a few reasons,” according to Michael S. Garshick, MD, a researcher, cardiologist, and director of the cardio-rheumatology program, New York University Langone Health.

An investigator who has participated in several studies evaluating the relationship between cardiovascular risk and psoriasis, Dr. Garshick said there is increasing interest in PCSK9 as a biomarker or even a mediator of inflammation independent of blood lipid levels.

“In psoriasis regarding PCSK9, we and others have shown PCSK9 is elevated in psoriatic lesion skin, and studies are starting to investigate the unique lipidomic profile in psoriasis,” Dr. Garshick said in an interview. The study he led that showed elevated PCSK9 levels in psoriatic skin was published in 2021 in the Journal of Investigative Dermatology.

While the Mendelian randomization provides only “an inference” that PCSK9 plays a role in mediating risk of psoriasis, Dr. Zhao and coauthors cited numerous studies linking elevated PCSK9 to psoriasis pathophysiology. This not only includes the elevated PCSK9 expression in psoriatic plaques as shown by Dr. Garshick and others but several sets of experimental evidence linking PCSK9 to inflammatory pathways, including upregulation of interleukin-17 and stimulation of macrophage activation.

While Dr. Zhao and coauthors suggested that clinical trials are now needed to test the potential of PCSK9 inhibitors to modify the risk of psoriasis, Dr. Garshick indicated that there are numerous variables to unravel in the relationship between elevated lipids, PCSK9, and psoriasis.

“In our own studies, we did see a statistical correlation between circulating PCSK9 and psoriasis severity,” Dr. Garshick said. But he added, “I think we are just beginning to understand the functions of circulating (extrahepatic) PCSK9 independent of lipid metabolism.”

While he is intrigued by the evidence that PCSK9 is linked to systemic inflammation, he pointed out that several medications used to treat dyslipidemias, such as statins, are associated with an anti-inflammatory effect.

This study “further emphasizes the need to conduct clinical trials treating dyslipidemia in psoriasis, including the targeting of PCSK9, whether it is with statins with lipid lowering and potential pleiotropic anti-inflammatory properties or PCSK9 inhibition,” he said. If positive, “both would be exciting.“

From a cardiologist’s point of view, there is an upside for including patients with psoriasis in lipid-lowering trials even if the effect on psoriasis is modest. Either way, “you still get the lipid-lowering benefit, which is important for reducing atherosclerotic cardiovascular disease,” Dr. Garshick said.

Dr. Zhao reported financial relationships with UCB, although UCB did not provide funding for this study. One author reported grants from Versus Arthritis and the National Institute for Health Research Manchester Biomedical Research Centre during the study, grants from Bristol Myers Squibb, Galapagos, and Pfizer, and personal fees from Chugai Roche outside the submitted work. No other disclosures were reported. The study was supported by grants from Versus Arthritis and the NIHR Manchester Biomedical Research Centre. Dr. Garshick reported financial relationships with AbbVie and Horizon Therapeutics.

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

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

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

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

Hidden in the Dec. 1, 2022, issue of the New England Journal of Medicine was a small article on using deferiprone for Parkinson’s disease.

The idea behind it makes sense. A key factor in Parkinson’s disease is a loss of cells in the substantia nigra. The cells that have been lost have a build-up of iron content, suggesting that iron contributes to their demise. Therefore, maybe using an iron chelating agent to remove it may help.

Like I said, it makes sense.

Unfortunately, it didn’t quite work that way. In spite of a clear reduction of nigrostriatal iron, compared with the placebo group, the treated patients had worse MDS-UPDRS scores over 36 weeks than those on the placebo.

Back to the drawing board.

I’m not criticizing the people who did the study – it seemed like a reasonable hypothesis, and testing it is the only way we find out if it’s correct. We learn just as much, if not more, from a negative study as from a positive one, incrementally working toward the answer with each.

We face the same thing with the amyloid theory in Alzheimer’s disease. Getting rid of amyloid should fix the problem.

But it doesn’t, at least not completely. Even lecanemab, the latest-and-greatest of treatments, only shows a 27% slowing in disease progression. This is certainly meaningful – I’m not knocking it – but we’re still far from a cure. To date we haven’t even stopped disease progression, let alone reversed it.

Although the new drugs have a remarkable mechanism of action, the clinical results aren’t nearly as good as one would expect if amyloid was the whole issue.

Which, at this point, it probably isn’t, anymore than nigrostriatal iron deposition is the sole cause of Parkinson’s disease.

In medicine, as in so many other things, there’s simply a lot that we don’t know yet. Right now we’re better able to find planets 27,700 light years away (SWEEPS-11) than we are at knowing the cause of neuronal changes in the person sitting across the desk from us. That’s not saying we won’t have the answers someday, it just means we don’t have them now.

I was in my 3rd year of medical school in January of 1992, (surgery rotation at the Omaha VA, to be specific) when the first definitive planet outside our solar system was identified. Today, 31 years later, the number of exoplanets stands at 5,297.

But the laws of physics are generally a lot more predictable than those of biology.

That doesn’t mean we won’t find the answers, or more effective treatments, eventually. But it will take more time, work, and studies – with both positive and negative results – to get there.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

Adhering to six healthy lifestyle behaviors is linked to slower memory decline in older adults, a large population-based study suggests.

Investigators found that a healthy diet, cognitive activity, regular physical exercise, not smoking, and abstaining from alcohol were significantly linked to slowed cognitive decline irrespective of APOE4 status.

After adjusting for health and socioeconomic factors, investigators found that each individual healthy behavior was associated with a slower-than-average decline in memory over a decade. A healthy diet emerged as the strongest deterrent, followed by cognitive activity and physical exercise.

“A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE4 allele,” study investigators led by Jianping Jia, MD, PhD, of the Innovation Center for Neurological Disorders and the department of neurology, Xuan Wu Hospital, Capital Medical University, Beijing, write.

“This study might offer important information to protect older adults against memory decline,” they add.

The study was published online in the BMJ.
 

Preventing memory decline

Memory “continuously declines as people age,” but age-related memory decline is not necessarily a prodrome of dementia and can “merely be senescent forgetfulness,” the investigators note. This can be “reversed or [can] become stable,” instead of progressing to a pathologic state.

Factors affecting memory include aging, APOE4 genotype, chronic diseases, and lifestyle patterns, with lifestyle “receiving increasing attention as a modifiable behavior.”

Nevertheless, few studies have focused on the impact of lifestyle on memory, and those that have are mostly cross-sectional and also “did not consider the interaction between a healthy lifestyle and genetic risk,” the researchers note.

To investigate, the researchers conducted a longitudinal study, known as the China Cognition and Aging Study, that considered genetic risk as well as lifestyle factors.

The study began in 2009 and concluded in 2019. Participants were evaluated and underwent neuropsychological testing in 2012, 2014, 2016, and at the study’s conclusion.

Participants (n = 29,072; mean [SD] age, 72.23 [6.61] years; 48.54% women; 20.43% APOE4 carriers) were required to have normal cognitive function at baseline. Data on those whose condition progressed to mild cognitive impairment (MCI) or dementia during the follow-up period were excluded after their diagnosis.

The Mini–Mental State Examination was used to assess global cognitive function. Memory function was assessed using the World Health Organization/University of California, Los Angeles Auditory Verbal Learning Test.

“Lifestyle” consisted of six modifiable factors: physical exercise (weekly frequency and total time), smoking (current, former, or never-smokers), alcohol consumption (never drank, drank occasionally, low to excess drinking, and heavy drinking), diet (daily intake of 12 food items: fruits, vegetables, fish, meat, dairy products, salt, oil, eggs, cereals, legumes, nuts, tea), cognitive activity (writing, reading, playing cards, mahjong, other games), and social contact (participating in meetings, attending parties, visiting friends/relatives, traveling, chatting online).

Participants’ lifestyles were scored on the basis of the number of healthy factors they engaged in.

Important for public health

During the 10-year period, 7,164 participants died, and 3,567 stopped participating.

Participants in the favorable and average groups showed slower memory decline per increased year of age (0.007 [0.005-0.009], P < .001; and 0.002 [0 .000-0.003], P = .033 points higher, respectively), compared with those in the unfavorable group.

Healthy diet had the strongest protective effect on memory.

‘Important, encouraging’ research

In a comment, Severine Sabia, PhD, a senior researcher at the Université Paris Cité, INSERM Institut National de la Santé et de la Recherche Medicalé, France, called the findings “important and encouraging.”

However, said Dr. Sabia, who was not involved with the study, “there remain important research questions that need to be investigated in order to identify key behaviors: which combination, the cutoff of risk, and when to intervene.”

Future research on prevention “should examine a wider range of possible risk factors” and should also “identify specific exposures associated with the greatest risk, while also considering the risk threshold and age at exposure for each one.”

In an accompanying editorial, Dr. Sabia and co-author Archana Singh-Manoux, PhD, note that the risk of cognitive decline and dementia are probably determined by multiple factors.

They liken it to the “multifactorial risk paradigm introduced by the Framingham study,” which has “led to a substantial reduction in cardiovascular disease.” A similar approach could be used with dementia prevention, they suggest.

The authors received support from the Xuanwu Hospital of Capital Medical University for the submitted work. One of the authors received a grant from the French National Research Agency. The other authors have disclosed no relevant financial relationships. Dr. Sabia received grant funding from the French National Research Agency. Dr. Singh-Manoux received grants from the National Institute on Aging of the National Institutes of Health.

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

Answer: Blue rubber bleb nevus syndrome.

Based on the history of hemangioma resection and vascular lesions in the small intestine, along with typical manifestations of chronic gastrointestinal bleeding, diagnosis of blue rubber bleb nevus syndrome (BRBNS) was made. According to an American College of Gastroenterology Clinical Guideline,¹ for patients with recurrence of small bowel bleeding, endoscopic management could be considered depending on the patient’s clinical course and response to prior therapy. Consequently, injections of lauromacrogol with SBE (single-balloon enteroscopy) were given (Figure D). Lesions that ranged from 1 to 2 cm were injected with 1-2 mL lauromacrogol until the mucosa turned white. Three SBEs had been performed in a 5-month period. A total of 20 lesions were successfully treated with lauromacrogol. The treated hemangiomas became small, and the site healed 5 months after treatment (Figures E and F). The patient has been followed for 1 year, and he remains in good clinical condition with his latest hemoglobin level at 110 g/L. No further blood transfusion is needed.

Gastroenterology (2019;157:311-2)

BRBNS is a rare disorder characterized by discrete venous malformations of varying size and appearance that are present on the skin and within the gastrointestinal tract.²With wider application of video capsule endoscopy (VCE) and the increase of image resolution, the detection rate and diagnostic accuracy of BRBNS are significantly improved. Treatment of BRBNS varies depending on the site, size, and number of lesions. Medication, surgery, and endoscopic therapy are currently clinically applied. The successful use of sirolimus was recently reported in the treatment of vascular lesions.³Sirolimus has potential adverse effects on renal function, bone marrow, and cholesterol metabolism, however. In consideration of the patient’s young age, we did not adopt this method. Surgical resection is more suitable for limited or life-threatening lesions. The lesions in this patient were mild and sporadic. Consequently, in this case, endoscopic injection of lauromacrogol was performed. This was the most complicated case of endoscopic treatment of BRBNS in our center and proved lauromacrogol injection was a feasible approach. According to a literature review, lauromacrogol has been used to treat vascular lesions for decades, but there is still no standard instruction for the dosage of lauromacrogol. We hope that our experience can be a reference for the endoscopic treatment of BRBNS.

References (add links)

1. Gerson LB et al. ACG clinical guideline: Diagnosis and management of small bowel bleeding. Am J Gastroenterol.

2. Felton SJ and Ferguson JE. Multiple cutaneous swellings associated with sudden collapse. JAMA.

3. Yuksekkaya H et al. Blue rubber bleb nevus syndrome: Successful treatment with sirolimus. Pediatrics.

Answer: Blue rubber bleb nevus syndrome.

Based on the history of hemangioma resection and vascular lesions in the small intestine, along with typical manifestations of chronic gastrointestinal bleeding, diagnosis of blue rubber bleb nevus syndrome (BRBNS) was made. According to an American College of Gastroenterology Clinical Guideline,¹ for patients with recurrence of small bowel bleeding, endoscopic management could be considered depending on the patient’s clinical course and response to prior therapy. Consequently, injections of lauromacrogol with SBE (single-balloon enteroscopy) were given (Figure D). Lesions that ranged from 1 to 2 cm were injected with 1-2 mL lauromacrogol until the mucosa turned white. Three SBEs had been performed in a 5-month period. A total of 20 lesions were successfully treated with lauromacrogol. The treated hemangiomas became small, and the site healed 5 months after treatment (Figures E and F). The patient has been followed for 1 year, and he remains in good clinical condition with his latest hemoglobin level at 110 g/L. No further blood transfusion is needed.

Gastroenterology (2019;157:311-2)

BRBNS is a rare disorder characterized by discrete venous malformations of varying size and appearance that are present on the skin and within the gastrointestinal tract.²With wider application of video capsule endoscopy (VCE) and the increase of image resolution, the detection rate and diagnostic accuracy of BRBNS are significantly improved. Treatment of BRBNS varies depending on the site, size, and number of lesions. Medication, surgery, and endoscopic therapy are currently clinically applied. The successful use of sirolimus was recently reported in the treatment of vascular lesions.³Sirolimus has potential adverse effects on renal function, bone marrow, and cholesterol metabolism, however. In consideration of the patient’s young age, we did not adopt this method. Surgical resection is more suitable for limited or life-threatening lesions. The lesions in this patient were mild and sporadic. Consequently, in this case, endoscopic injection of lauromacrogol was performed. This was the most complicated case of endoscopic treatment of BRBNS in our center and proved lauromacrogol injection was a feasible approach. According to a literature review, lauromacrogol has been used to treat vascular lesions for decades, but there is still no standard instruction for the dosage of lauromacrogol. We hope that our experience can be a reference for the endoscopic treatment of BRBNS.

References (add links)

1. Gerson LB et al. ACG clinical guideline: Diagnosis and management of small bowel bleeding. Am J Gastroenterol.

2. Felton SJ and Ferguson JE. Multiple cutaneous swellings associated with sudden collapse. JAMA.

3. Yuksekkaya H et al. Blue rubber bleb nevus syndrome: Successful treatment with sirolimus. Pediatrics.

Answer: Blue rubber bleb nevus syndrome.

Based on the history of hemangioma resection and vascular lesions in the small intestine, along with typical manifestations of chronic gastrointestinal bleeding, diagnosis of blue rubber bleb nevus syndrome (BRBNS) was made. According to an American College of Gastroenterology Clinical Guideline,¹ for patients with recurrence of small bowel bleeding, endoscopic management could be considered depending on the patient’s clinical course and response to prior therapy. Consequently, injections of lauromacrogol with SBE (single-balloon enteroscopy) were given (Figure D). Lesions that ranged from 1 to 2 cm were injected with 1-2 mL lauromacrogol until the mucosa turned white. Three SBEs had been performed in a 5-month period. A total of 20 lesions were successfully treated with lauromacrogol. The treated hemangiomas became small, and the site healed 5 months after treatment (Figures E and F). The patient has been followed for 1 year, and he remains in good clinical condition with his latest hemoglobin level at 110 g/L. No further blood transfusion is needed.

Gastroenterology (2019;157:311-2)

BRBNS is a rare disorder characterized by discrete venous malformations of varying size and appearance that are present on the skin and within the gastrointestinal tract.²With wider application of video capsule endoscopy (VCE) and the increase of image resolution, the detection rate and diagnostic accuracy of BRBNS are significantly improved. Treatment of BRBNS varies depending on the site, size, and number of lesions. Medication, surgery, and endoscopic therapy are currently clinically applied. The successful use of sirolimus was recently reported in the treatment of vascular lesions.³Sirolimus has potential adverse effects on renal function, bone marrow, and cholesterol metabolism, however. In consideration of the patient’s young age, we did not adopt this method. Surgical resection is more suitable for limited or life-threatening lesions. The lesions in this patient were mild and sporadic. Consequently, in this case, endoscopic injection of lauromacrogol was performed. This was the most complicated case of endoscopic treatment of BRBNS in our center and proved lauromacrogol injection was a feasible approach. According to a literature review, lauromacrogol has been used to treat vascular lesions for decades, but there is still no standard instruction for the dosage of lauromacrogol. We hope that our experience can be a reference for the endoscopic treatment of BRBNS.

References (add links)

1. Gerson LB et al. ACG clinical guideline: Diagnosis and management of small bowel bleeding. Am J Gastroenterol.

2. Felton SJ and Ferguson JE. Multiple cutaneous swellings associated with sudden collapse. JAMA.

3. Yuksekkaya H et al. Blue rubber bleb nevus syndrome: Successful treatment with sirolimus. Pediatrics.

New renin-angiotensin-system (RAS) inhibitor therapy using sacubitril-valsartan (Entresto) is no more likely to cause angioedema than starting out with an ACE inhibitor or angiotensin receptor blocker (ARB).

But the risk climbs when such patients start on an ACE inhibitor or ARB and then switch to sacubitril-valsartan, compared with those prescribed the newer drug, the only available angiotensin receptor-neprilysin inhibitor (ARNI), in the first place.

Those findings and others from a large database analysis, by researchers at the Food and Drug Administration and Harvard Medical School, may clarify and help alleviate a residual safety concern about the ARNI – that it might promote angioedema – that persists after the drug’s major HF trials.  

The angioedema risk increased the most right after the switch to the ARNI from one of the older RAS inhibitors. For example, the overall risk doubled for patients who started with an ARB then switched to sacubitril-valsartan, compared with those who started on the newer drug. But it went up about 2.5 times during the first 14 days after the switch.

A similar pattern emerged for ACE inhibitors, but the increased angioedema risk reached significance only within 2 weeks of the switch from an ACE inhibitor to sacubitril-valsartan compared to starting on the latter.

The analysis, based on data from the FDA’s Sentinel adverse event reporting system, was published in the Journal of the American College of Cardiology.
 

A rare complication, but ...

Angioedema was rare overall in the study, with an unadjusted rate of about 6.75 per 1,000 person-years for users of ACE inhibitors, less than half that rate for ARB users, and only one-fifth that rate for sacubitril-valsartan recipients.

But even a rare complication can be a worry for drugs as widely used as RAS inhibitors. And it’s not unusual for patients cautiously started on an ACE inhibitor or ARB to be switched to sacubitril-valsartan, which is only recently a core guideline–recommended therapy for HF with reduced ejection fraction.

Such patients transitioning to the ARNI, the current study suggests, should probably be watched closely for signs of angioedema for 2 weeks but especially during the first few days. Indeed, the study’s event curves show most of the extra risk “popping up” right after the switch to sacubitril-valsartan, lead author Efe Eworuke, PhD, told this news organization.

The ARNI’s labeling, which states the drug should follow ACE inhibitors only after 36-hour washout period, “has done justice to this issue,” she said. But “whether clinicians are adhering to that, we can’t tell.”

Potentially, patients who miss the 36-hour washout between ACE inhibitors or ARBs and sacubitril-valsartan may account for the excess angioedema risk seen in the analysis, said Dr. Eworuke, with the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md.

But the analysis doesn’t nail down the window of excess risk to only 36 hours. It suggests that patients switching to the ARNI – even those pausing for 36 hours in between drugs – should probably be monitored “2 weeks or longer,” she said. “They could still have angioedema after the washout period.”

Indeed, the “timing of the switch may be critical,” according to an editorial accompanying the report. “Perhaps a longer initial exposure period of ACE inhibitor or ARB,” beyond 2 weeks, “should be considered before switching to an ARNI,” contended Robert L. Page II, PharmD, MSPH, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora.

American Heart Association

Moreover, he wrote, the study suggests that “initiation of an ARNI de novo may be safer compared with trialing an ACE inhibitor or ARB then switching to an ARNI,” and “should be a consideration when beginning guideline-directed medical therapy for patients with HF.”
 

New RAS inhibition with ARNI ‘protective’

Compared with ARNI “new users” who had not received any RAS inhibitor in the prior 6 months, patients in the study who switched from an ACE inhibitor to ARNI (41,548 matched pairs) showed a hazard ratio (HR) for angioedema of 1.62 (95% confidence interval [CI], 0.91-2.89), that is, only a “trend,” the report states.

But that trend became significant when the analysis considered only angioedema cases in the first 14 days after the drug switch: HR, 1.98 (95% CI, 1.11-3.53).

Those switching from an ARB to ARNI, compared with ARNI new users (37,893 matched pairs), showed a significant HR for angioedema of 2.03 (95% CI, 1.16-3.54). The effect was more pronounced when considering only angioedema arising in the first 2 weeks: HR, 2.45 (95% CI, 1.36-4.43).

Compared with new use of ACE inhibitors, new ARNI use (41,998 matched pairs) was “protective,” the report states, with an HR for angioedema of 0.18 (95% CI, 0.11-0.29). So was a switch from ACE inhibitors to the ARNI (69,639 matched pairs), with an HR of 0.31 (95% CI, 0.23-0.43).

But compared with starting with an ARB, ARNI new use (43,755 matched pairs) had a null effect on angioedema risk, HR, 0.59 (95% CI, 0.35-1.01); as did switching from an ARB to ARNI (49,137 matched pairs), HR, 0.85 (95% CI, 0.58-1.26).

The analysis has limitations, Dr. Eworuke acknowledged. The comparator groups probably differed in unknown ways given the limits of propensity matching, for example, and because the FDA’s Sentinel system data can reflect only cases that are reported, the study probably underestimates the true prevalence of angioedema.

For example, a patient may see a clinician for a milder case that resolves without a significant intervention, she noted. But “those types of angioedema would not have been captured by our study.”

Dr. Eworuke disclosed that her comments reflect her views and are not those of the Food and Drug Administration; she and the other authors, as well as editorialist Dr. Page, report no relevant financial relationships.

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

New renin-angiotensin-system (RAS) inhibitor therapy using sacubitril-valsartan (Entresto) is no more likely to cause angioedema than starting out with an ACE inhibitor or angiotensin receptor blocker (ARB).

But the risk climbs when such patients start on an ACE inhibitor or ARB and then switch to sacubitril-valsartan, compared with those prescribed the newer drug, the only available angiotensin receptor-neprilysin inhibitor (ARNI), in the first place.

Those findings and others from a large database analysis, by researchers at the Food and Drug Administration and Harvard Medical School, may clarify and help alleviate a residual safety concern about the ARNI – that it might promote angioedema – that persists after the drug’s major HF trials.  

The angioedema risk increased the most right after the switch to the ARNI from one of the older RAS inhibitors. For example, the overall risk doubled for patients who started with an ARB then switched to sacubitril-valsartan, compared with those who started on the newer drug. But it went up about 2.5 times during the first 14 days after the switch.

A similar pattern emerged for ACE inhibitors, but the increased angioedema risk reached significance only within 2 weeks of the switch from an ACE inhibitor to sacubitril-valsartan compared to starting on the latter.

The analysis, based on data from the FDA’s Sentinel adverse event reporting system, was published in the Journal of the American College of Cardiology.
 

A rare complication, but ...

Angioedema was rare overall in the study, with an unadjusted rate of about 6.75 per 1,000 person-years for users of ACE inhibitors, less than half that rate for ARB users, and only one-fifth that rate for sacubitril-valsartan recipients.

But even a rare complication can be a worry for drugs as widely used as RAS inhibitors. And it’s not unusual for patients cautiously started on an ACE inhibitor or ARB to be switched to sacubitril-valsartan, which is only recently a core guideline–recommended therapy for HF with reduced ejection fraction.

Such patients transitioning to the ARNI, the current study suggests, should probably be watched closely for signs of angioedema for 2 weeks but especially during the first few days. Indeed, the study’s event curves show most of the extra risk “popping up” right after the switch to sacubitril-valsartan, lead author Efe Eworuke, PhD, told this news organization.

The ARNI’s labeling, which states the drug should follow ACE inhibitors only after 36-hour washout period, “has done justice to this issue,” she said. But “whether clinicians are adhering to that, we can’t tell.”

Potentially, patients who miss the 36-hour washout between ACE inhibitors or ARBs and sacubitril-valsartan may account for the excess angioedema risk seen in the analysis, said Dr. Eworuke, with the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md.

But the analysis doesn’t nail down the window of excess risk to only 36 hours. It suggests that patients switching to the ARNI – even those pausing for 36 hours in between drugs – should probably be monitored “2 weeks or longer,” she said. “They could still have angioedema after the washout period.”

Indeed, the “timing of the switch may be critical,” according to an editorial accompanying the report. “Perhaps a longer initial exposure period of ACE inhibitor or ARB,” beyond 2 weeks, “should be considered before switching to an ARNI,” contended Robert L. Page II, PharmD, MSPH, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora.

American Heart Association

Moreover, he wrote, the study suggests that “initiation of an ARNI de novo may be safer compared with trialing an ACE inhibitor or ARB then switching to an ARNI,” and “should be a consideration when beginning guideline-directed medical therapy for patients with HF.”
 

New RAS inhibition with ARNI ‘protective’

Compared with ARNI “new users” who had not received any RAS inhibitor in the prior 6 months, patients in the study who switched from an ACE inhibitor to ARNI (41,548 matched pairs) showed a hazard ratio (HR) for angioedema of 1.62 (95% confidence interval [CI], 0.91-2.89), that is, only a “trend,” the report states.

But that trend became significant when the analysis considered only angioedema cases in the first 14 days after the drug switch: HR, 1.98 (95% CI, 1.11-3.53).

Those switching from an ARB to ARNI, compared with ARNI new users (37,893 matched pairs), showed a significant HR for angioedema of 2.03 (95% CI, 1.16-3.54). The effect was more pronounced when considering only angioedema arising in the first 2 weeks: HR, 2.45 (95% CI, 1.36-4.43).

Compared with new use of ACE inhibitors, new ARNI use (41,998 matched pairs) was “protective,” the report states, with an HR for angioedema of 0.18 (95% CI, 0.11-0.29). So was a switch from ACE inhibitors to the ARNI (69,639 matched pairs), with an HR of 0.31 (95% CI, 0.23-0.43).

But compared with starting with an ARB, ARNI new use (43,755 matched pairs) had a null effect on angioedema risk, HR, 0.59 (95% CI, 0.35-1.01); as did switching from an ARB to ARNI (49,137 matched pairs), HR, 0.85 (95% CI, 0.58-1.26).

The analysis has limitations, Dr. Eworuke acknowledged. The comparator groups probably differed in unknown ways given the limits of propensity matching, for example, and because the FDA’s Sentinel system data can reflect only cases that are reported, the study probably underestimates the true prevalence of angioedema.

For example, a patient may see a clinician for a milder case that resolves without a significant intervention, she noted. But “those types of angioedema would not have been captured by our study.”

Dr. Eworuke disclosed that her comments reflect her views and are not those of the Food and Drug Administration; she and the other authors, as well as editorialist Dr. Page, report no relevant financial relationships.

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

New renin-angiotensin-system (RAS) inhibitor therapy using sacubitril-valsartan (Entresto) is no more likely to cause angioedema than starting out with an ACE inhibitor or angiotensin receptor blocker (ARB).

But the risk climbs when such patients start on an ACE inhibitor or ARB and then switch to sacubitril-valsartan, compared with those prescribed the newer drug, the only available angiotensin receptor-neprilysin inhibitor (ARNI), in the first place.

Those findings and others from a large database analysis, by researchers at the Food and Drug Administration and Harvard Medical School, may clarify and help alleviate a residual safety concern about the ARNI – that it might promote angioedema – that persists after the drug’s major HF trials.  

The angioedema risk increased the most right after the switch to the ARNI from one of the older RAS inhibitors. For example, the overall risk doubled for patients who started with an ARB then switched to sacubitril-valsartan, compared with those who started on the newer drug. But it went up about 2.5 times during the first 14 days after the switch.

A similar pattern emerged for ACE inhibitors, but the increased angioedema risk reached significance only within 2 weeks of the switch from an ACE inhibitor to sacubitril-valsartan compared to starting on the latter.

The analysis, based on data from the FDA’s Sentinel adverse event reporting system, was published in the Journal of the American College of Cardiology.
 

A rare complication, but ...

Angioedema was rare overall in the study, with an unadjusted rate of about 6.75 per 1,000 person-years for users of ACE inhibitors, less than half that rate for ARB users, and only one-fifth that rate for sacubitril-valsartan recipients.

But even a rare complication can be a worry for drugs as widely used as RAS inhibitors. And it’s not unusual for patients cautiously started on an ACE inhibitor or ARB to be switched to sacubitril-valsartan, which is only recently a core guideline–recommended therapy for HF with reduced ejection fraction.

Such patients transitioning to the ARNI, the current study suggests, should probably be watched closely for signs of angioedema for 2 weeks but especially during the first few days. Indeed, the study’s event curves show most of the extra risk “popping up” right after the switch to sacubitril-valsartan, lead author Efe Eworuke, PhD, told this news organization.

The ARNI’s labeling, which states the drug should follow ACE inhibitors only after 36-hour washout period, “has done justice to this issue,” she said. But “whether clinicians are adhering to that, we can’t tell.”

Potentially, patients who miss the 36-hour washout between ACE inhibitors or ARBs and sacubitril-valsartan may account for the excess angioedema risk seen in the analysis, said Dr. Eworuke, with the FDA’s Center for Drug Evaluation and Research, Silver Spring, Md.

But the analysis doesn’t nail down the window of excess risk to only 36 hours. It suggests that patients switching to the ARNI – even those pausing for 36 hours in between drugs – should probably be monitored “2 weeks or longer,” she said. “They could still have angioedema after the washout period.”

Indeed, the “timing of the switch may be critical,” according to an editorial accompanying the report. “Perhaps a longer initial exposure period of ACE inhibitor or ARB,” beyond 2 weeks, “should be considered before switching to an ARNI,” contended Robert L. Page II, PharmD, MSPH, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora.

American Heart Association

Moreover, he wrote, the study suggests that “initiation of an ARNI de novo may be safer compared with trialing an ACE inhibitor or ARB then switching to an ARNI,” and “should be a consideration when beginning guideline-directed medical therapy for patients with HF.”
 

New RAS inhibition with ARNI ‘protective’

Compared with ARNI “new users” who had not received any RAS inhibitor in the prior 6 months, patients in the study who switched from an ACE inhibitor to ARNI (41,548 matched pairs) showed a hazard ratio (HR) for angioedema of 1.62 (95% confidence interval [CI], 0.91-2.89), that is, only a “trend,” the report states.

But that trend became significant when the analysis considered only angioedema cases in the first 14 days after the drug switch: HR, 1.98 (95% CI, 1.11-3.53).

Those switching from an ARB to ARNI, compared with ARNI new users (37,893 matched pairs), showed a significant HR for angioedema of 2.03 (95% CI, 1.16-3.54). The effect was more pronounced when considering only angioedema arising in the first 2 weeks: HR, 2.45 (95% CI, 1.36-4.43).

Compared with new use of ACE inhibitors, new ARNI use (41,998 matched pairs) was “protective,” the report states, with an HR for angioedema of 0.18 (95% CI, 0.11-0.29). So was a switch from ACE inhibitors to the ARNI (69,639 matched pairs), with an HR of 0.31 (95% CI, 0.23-0.43).

But compared with starting with an ARB, ARNI new use (43,755 matched pairs) had a null effect on angioedema risk, HR, 0.59 (95% CI, 0.35-1.01); as did switching from an ARB to ARNI (49,137 matched pairs), HR, 0.85 (95% CI, 0.58-1.26).

The analysis has limitations, Dr. Eworuke acknowledged. The comparator groups probably differed in unknown ways given the limits of propensity matching, for example, and because the FDA’s Sentinel system data can reflect only cases that are reported, the study probably underestimates the true prevalence of angioedema.

For example, a patient may see a clinician for a milder case that resolves without a significant intervention, she noted. But “those types of angioedema would not have been captured by our study.”

Dr. Eworuke disclosed that her comments reflect her views and are not those of the Food and Drug Administration; she and the other authors, as well as editorialist Dr. Page, report no relevant financial relationships.

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