Mixed Topics

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

Social media is rife with content promoting colon cleansing as a way to shed toxins and fix everything from chronic fatigue and overweight to weak immunity and skin problems.

Even doctors who aren’t hip to the latest TikTok trends may not be able to avoid the hype. That’s because patients are bringing up colon cleansing during their office visit.

“Patients often raise questions about colonics or detox teas, especially when these gain traction on social media platforms like TikTok,” said Tauseef Ali, MD, AGAF, medical executive director of SSM Health Digestive Care at St. Anthony Hospital in Oklahoma City. “Interest typically comes in waves, closely tied to the latest online trends.”

That means gastroenterologists need to be prepared when they’re asked if the latest product — whether it’s colon hydrotherapy, a detox drink or pill, or an enema — being touted by influencers is good for their health. And it’s not just patients who are asking.

“Sometimes we’ll get a message from primary care,” Mohammad Bilal, MD, associate professor of medicine and director of Bariatric and Third Space Endoscopy at the University of Colorado Anschutz Medical Campus in Aurora, Colorado, told GI & Hepatology News. They’re getting the same questions from patients, and they want to know if colon cleansing that’s not connected with a colonoscopy exam has any benefits for overall health or specific health conditions.

The answer is no, and patients are more likely to believe that when physicians explain it using good information. Here is how Ali, Bilal, and professional organizations advise doctors to approach the issue.

 

What Exactly Is a Colon Cleanse?

Colon cleanses come in a variety of forms. Colonic irrigation, also called colon hydrotherapy, involves inserting a tube into the rectum and flushing out the colon with a large amount of fluid. Enemas do the same but use a small amount of liquid, and some product instructions tell the user to “hold it” for a designated amount of time before expelling colon contents.

Other cleanses, often called detoxing cleanses, are laxatives or herbal teas that users drink — and then stay close to the bathroom. Detox regimens and diets also are mentioned as a way to remove toxins from the body, improve health, and promote well-being.

 

Why Do Patients Use Them?

“Many patients describe a desire for ‘cleanliness,’ ‘detoxification,’ or to ‘feel lighter,’” Ali told GI & Hepatology News.

The claims on social media promote all of this and more — and well-known influencers make it all sound even more attractive.

“These motivations are often rooted in the cultural belief that the colon accumulates harmful toxins that must be flushed out,” Ali said. “This idea is not supported by scientific evidence. The body’s natural detox systems, primarily the liver and kidneys, already perform this function effectively.”

Bilal said that in recent years, he has noticed more awareness in general about the importance of gut health. “When there’s awareness, people often go to the other extreme,” he said.

Where Is the Evidence?

The National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health, warns on an information page that both cleansing and detox programs can be unsafe and falsely advertised.

While searches of medical literature turn up few studies, the NCCIH information points to a 2014 review that concluded that there is no compelling research to support the use of detox diets for managing weight or eliminating toxins. A 2017 review found juicing and detox regimens can cause weight loss initially but then lead to weight gain once a normal diet is resumed.

A systematic review of research on the safety and effectiveness of self-administered coffee enemas found nine case reports describing adverse events: seven reported colitis after the enema, and two reported more critical adverse events. All nine reports warned against the procedure. The researchers found no study reporting the effectiveness of coffee enemas.

The NCCIH information also notes that there is “limited clinical evidence validating colonic irrigation and insufficient evidence for its prescribed uses.”

 

Are Cleanses Regulated?

Some over-the-counter colon cleansing products are viewed as dietary supplements, giving the FDA authority to regulate them and take action under the Dietary Supplement Health and Education Act of 1994.

Certain products promoted as colon cleanses, such as laxatives, are regulated by the FDA as over-the-counter drugs and must meet safety and other requirements.

Colonic irrigation systems meant for cleansing before radiologic or endoscopic exams are class II devices — subject to 510(k) premarket notification requirements before marketing — whereas systems intended for other uses, such as routine colon cleansing for general well-being, are regarded as class III devices — subject to premarket approval requirements — according to an FDA spokesperson. To date, the FDA has not approved any colonic irrigation devices for the latter use, the spokesperson said.

For instance, the FDA warned consumers not to use a product promoted for colon cleansing after finding it contained tadalafil, the active ingredient in an FDA-approved drug for erectile dysfunction. The FDA has also issued numerous warning letters to the makers of colon cleansing devices, as they are not approved for this purpose.

The Federal Trade Commission can also take action specifically if the claims about the benefits and safety of products — including supplements, foods, over-the-counter drugs, or health equipment — are false, misleading, or not supported by science.

 

What Are the Dangers?

Cleanse and detox products come with many risks, including electrolyte imbalances, dehydration, and infections, Ali said. With colonic irrigation, there is a risk for rectal perforation. Products also may disrupt the gut microbiome, and some can interact with medications or worsen underlying health conditions, he added.

“It’s important for patients to be aware of these risks before considering nonmedical ‘cleaning’ methods,” he said.

At worst, patients risk fatality, Ali noted. He recalled a young patient who began using a vegetable enema as a detox. As it was being administered, the colon ruptured. The patient was admitted as a medical emergency and required surgery. Fortunately, the patient survived, but the incident could have proven fatal, Ali said.

 

Educating Patients

Because patients often don’t think of herbal cleanses, detox teas, and over-the-counter powders as supplements, Ali said it’s important to ask them about everything they take.

One way to frame this question is to ask if they are consuming any over-the-counter supplements or any other remedies, he said, and perhaps ask directly about any cleanses they are doing.

When patients ask him about colon cleanses, Ali explains the difference between evidence-based colonoscopy preparation and unregulated “cleanses.” Most patients respond to that approach, he said. Indeed, AGA and other GI societies updated their recommendations on optimizing bowel preparation quality for colonoscopy.

“Still, the appeal of quick fixes of social media trends can sometimes outweigh medical advice,” Ali said. He depends on building trusted relationships and reinforcing the message over time and finds that helps patients make informed and healthier choices.

Bilal, too, explains to patients that cleanses are unnecessary and educates them about what to do instead:

• Eat a  containing the recommended amount of  (22-34 g, depending on age and gender).
• For , follow a bowel regimen advised by your doctor.
• If gastrointestinal issues persist, get a medical checkup.
• Get any unexplained constipation or  checked out by a doctor.

Taking a careful history can pay off, Ali has found. He questioned a patient complaining of abdominal discomfort whose testing found unexpectedly elevated liver enzymes and found she had been using an herbal “cleanse tea” found online. Within 4 weeks of stopping it, her liver enzymes normalized. “Thankfully, she made a full recovery — and she never touched those remedies again,” he said.

Ali had no relevant disclosures. Bilal reported consulting for Boston Scientific, Cook Medical, and Steris.

 

A version of this article appeared on Medscape.com.

THE DIAGNOSIS: Gouty Tophus

The lesion was excised and sent for histopathologic examination (eFigures 1 and 2), revealing aggregates of feathery, amorphous, pale-pink material, which confirmed the diagnosis of gouty tophus. The surgical site was left to heal by secondary intention. Upon further evaluation, the patient reported recurrent monoarticular joint pain in the ankles and feet, and laboratory workup revealed elevated serum uric acid. He was advised to follow up with his primary care physician to discuss systemic treatment options for gout.

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate monohydrate crystals in the joints, soft tissue, and bone due to elevated serum uric acid. Uric acid is the final product of purine metabolism, and serum levels may be elevated due to excess production or underexcretion. Multiple genetic, environmental, and metabolic factors influence these processes.¹ Collections of monosodium urate crystals may develop intra- or extra-articularly, the latter of which are known as gouty tophi. These nodules have a classic chalklike consistency and typically are seen in patients with untreated gout starting approximately 10 years after the first flare. The most common locations for subcutaneous gouty tophi are acral sites (eg, fingertips, ears) as well as the wrists, knees, and elbows (olecranon bursae). Rarely, gouty panniculitis also may develop.²

Histopathology of gouty tophi reveals nodular aggregates of acellular, amorphous, pale-pink material surrounded by palisading histiocytes and multinucleated giant cells. The presence of needlelike monosodium urate crystals, which display negative birefringence, is diagnostic. Unfortunately, these crystals are destroyed in routine formalin processing.³

There are limited data regarding treatment of gouty tophi. Urate-lowering systemic medications such as pegloticase may be beneficial, but more data are needed.⁴ We pursued surgical excision in our case for definitive diagnosis; however, it is not a common treatment for gouty tophi. Typically, urate-lowering therapy is utilized to resolve or shrink lesions over time.⁵

The differential diagnosis for gouty tophi includes epidermal inclusion cyst (EIC), the most common type of cutaneous cyst. Though EICs can manifest anywhere on the body, they are not as common on the ears as gouty tophi. Epidermal inclusion cysts clinically manifest as soft subcutaneous nodules, and a central punctum often is noted. These lesions are derived from the follicular infundibulum and histologically are characterized by a cystic cavity lined by a stratified squamous epithelium with a granular layer. The cavity contains loose laminated keratin material.⁶

Pseudocyst of the auricle is a benign cystic swelling of the pinna that can develop spontaneously but most often manifests following trauma to the area, which is believed to separate the tissue planes in the cartilage, allowing fluid to accumulate. This lesion typically is asymptomatic, though some patients report mild tenderness.⁷ Histology shows a cystic structure within the cartilage without an epithelial lining, and a perivascular inflammatory response often is observed.⁸

Pilomatricoma, also known as pilomatrixoma, is a benign tumor derived from the hair follicle matrix that manifests as a firm, slow-growing, painless subcutaneous nodule. It most often is found on the head and neck, commonly in the periauricular area.⁹ Though rare, it has been found on the auricle and external auditory canal.¹⁰ Histologically, pilomatricomas are well-defined tumors containing internal trabeculae. They contain populations of basaloid and ghost cells and often calcify, sometimes with resultant bone formation.⁹

Dermoid cysts are benign tumors that develop along lines of embryonic closure and often are diagnosed at birth or in early childhood. They most commonly manifest on the head and neck, typically in the supraorbital area. Rarely, they have been reported on the ear.⁶ Dermoid cysts may resemble EICs clinically and histopathologically, except that the cyst wall contains mature adnexal structures such as hair follicles and sebaceous glands.

THE DIAGNOSIS: Gouty Tophus

The lesion was excised and sent for histopathologic examination (eFigures 1 and 2), revealing aggregates of feathery, amorphous, pale-pink material, which confirmed the diagnosis of gouty tophus. The surgical site was left to heal by secondary intention. Upon further evaluation, the patient reported recurrent monoarticular joint pain in the ankles and feet, and laboratory workup revealed elevated serum uric acid. He was advised to follow up with his primary care physician to discuss systemic treatment options for gout.

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate monohydrate crystals in the joints, soft tissue, and bone due to elevated serum uric acid. Uric acid is the final product of purine metabolism, and serum levels may be elevated due to excess production or underexcretion. Multiple genetic, environmental, and metabolic factors influence these processes.¹ Collections of monosodium urate crystals may develop intra- or extra-articularly, the latter of which are known as gouty tophi. These nodules have a classic chalklike consistency and typically are seen in patients with untreated gout starting approximately 10 years after the first flare. The most common locations for subcutaneous gouty tophi are acral sites (eg, fingertips, ears) as well as the wrists, knees, and elbows (olecranon bursae). Rarely, gouty panniculitis also may develop.²

Histopathology of gouty tophi reveals nodular aggregates of acellular, amorphous, pale-pink material surrounded by palisading histiocytes and multinucleated giant cells. The presence of needlelike monosodium urate crystals, which display negative birefringence, is diagnostic. Unfortunately, these crystals are destroyed in routine formalin processing.³

There are limited data regarding treatment of gouty tophi. Urate-lowering systemic medications such as pegloticase may be beneficial, but more data are needed.⁴ We pursued surgical excision in our case for definitive diagnosis; however, it is not a common treatment for gouty tophi. Typically, urate-lowering therapy is utilized to resolve or shrink lesions over time.⁵

The differential diagnosis for gouty tophi includes epidermal inclusion cyst (EIC), the most common type of cutaneous cyst. Though EICs can manifest anywhere on the body, they are not as common on the ears as gouty tophi. Epidermal inclusion cysts clinically manifest as soft subcutaneous nodules, and a central punctum often is noted. These lesions are derived from the follicular infundibulum and histologically are characterized by a cystic cavity lined by a stratified squamous epithelium with a granular layer. The cavity contains loose laminated keratin material.⁶

Pseudocyst of the auricle is a benign cystic swelling of the pinna that can develop spontaneously but most often manifests following trauma to the area, which is believed to separate the tissue planes in the cartilage, allowing fluid to accumulate. This lesion typically is asymptomatic, though some patients report mild tenderness.⁷ Histology shows a cystic structure within the cartilage without an epithelial lining, and a perivascular inflammatory response often is observed.⁸

Pilomatricoma, also known as pilomatrixoma, is a benign tumor derived from the hair follicle matrix that manifests as a firm, slow-growing, painless subcutaneous nodule. It most often is found on the head and neck, commonly in the periauricular area.⁹ Though rare, it has been found on the auricle and external auditory canal.¹⁰ Histologically, pilomatricomas are well-defined tumors containing internal trabeculae. They contain populations of basaloid and ghost cells and often calcify, sometimes with resultant bone formation.⁹

Dermoid cysts are benign tumors that develop along lines of embryonic closure and often are diagnosed at birth or in early childhood. They most commonly manifest on the head and neck, typically in the supraorbital area. Rarely, they have been reported on the ear.⁶ Dermoid cysts may resemble EICs clinically and histopathologically, except that the cyst wall contains mature adnexal structures such as hair follicles and sebaceous glands.

THE DIAGNOSIS: Gouty Tophus

The lesion was excised and sent for histopathologic examination (eFigures 1 and 2), revealing aggregates of feathery, amorphous, pale-pink material, which confirmed the diagnosis of gouty tophus. The surgical site was left to heal by secondary intention. Upon further evaluation, the patient reported recurrent monoarticular joint pain in the ankles and feet, and laboratory workup revealed elevated serum uric acid. He was advised to follow up with his primary care physician to discuss systemic treatment options for gout.

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate monohydrate crystals in the joints, soft tissue, and bone due to elevated serum uric acid. Uric acid is the final product of purine metabolism, and serum levels may be elevated due to excess production or underexcretion. Multiple genetic, environmental, and metabolic factors influence these processes.¹ Collections of monosodium urate crystals may develop intra- or extra-articularly, the latter of which are known as gouty tophi. These nodules have a classic chalklike consistency and typically are seen in patients with untreated gout starting approximately 10 years after the first flare. The most common locations for subcutaneous gouty tophi are acral sites (eg, fingertips, ears) as well as the wrists, knees, and elbows (olecranon bursae). Rarely, gouty panniculitis also may develop.²

Histopathology of gouty tophi reveals nodular aggregates of acellular, amorphous, pale-pink material surrounded by palisading histiocytes and multinucleated giant cells. The presence of needlelike monosodium urate crystals, which display negative birefringence, is diagnostic. Unfortunately, these crystals are destroyed in routine formalin processing.³

There are limited data regarding treatment of gouty tophi. Urate-lowering systemic medications such as pegloticase may be beneficial, but more data are needed.⁴ We pursued surgical excision in our case for definitive diagnosis; however, it is not a common treatment for gouty tophi. Typically, urate-lowering therapy is utilized to resolve or shrink lesions over time.⁵

The differential diagnosis for gouty tophi includes epidermal inclusion cyst (EIC), the most common type of cutaneous cyst. Though EICs can manifest anywhere on the body, they are not as common on the ears as gouty tophi. Epidermal inclusion cysts clinically manifest as soft subcutaneous nodules, and a central punctum often is noted. These lesions are derived from the follicular infundibulum and histologically are characterized by a cystic cavity lined by a stratified squamous epithelium with a granular layer. The cavity contains loose laminated keratin material.⁶

Pseudocyst of the auricle is a benign cystic swelling of the pinna that can develop spontaneously but most often manifests following trauma to the area, which is believed to separate the tissue planes in the cartilage, allowing fluid to accumulate. This lesion typically is asymptomatic, though some patients report mild tenderness.⁷ Histology shows a cystic structure within the cartilage without an epithelial lining, and a perivascular inflammatory response often is observed.⁸

Pilomatricoma, also known as pilomatrixoma, is a benign tumor derived from the hair follicle matrix that manifests as a firm, slow-growing, painless subcutaneous nodule. It most often is found on the head and neck, commonly in the periauricular area.⁹ Though rare, it has been found on the auricle and external auditory canal.¹⁰ Histologically, pilomatricomas are well-defined tumors containing internal trabeculae. They contain populations of basaloid and ghost cells and often calcify, sometimes with resultant bone formation.⁹

Dermoid cysts are benign tumors that develop along lines of embryonic closure and often are diagnosed at birth or in early childhood. They most commonly manifest on the head and neck, typically in the supraorbital area. Rarely, they have been reported on the ear.⁶ Dermoid cysts may resemble EICs clinically and histopathologically, except that the cyst wall contains mature adnexal structures such as hair follicles and sebaceous glands.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

Hi, everyone. I’m Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

The receding of the pandemic and the understandable desire to return to normalcy has made COVID-19 vaccines a lower priority for many of our patients. However, family physicians should keep in mind that from October 1, 2024, to September 6, 2025, COVID-19 was responsible for an estimated 3.2 to 4.6 million outpatient visits, 360,000 to 520,000 hospitalizations, and 42,000 to 60,000 deaths.

In a previous commentary, I discussed the worsening disconnect between the evidence supporting the effectiveness and safety of vaccinations and increasing reluctance of patients and parents to receive them, fueled by misinformation from federal health agencies and the packing of the Advisory Committee on Immunization Practices (ACIP) with vaccine skeptics. Since then, Secretary of Health and Human Services (HHS), Robert F. Kennedy, Jr, has fired Dr Susan Monarez, his handpicked director of the CDC. This caused three senior CDC officials to resign in protest and precipitated further turmoil at the embattled agency. 

The FDA has approved 3 updated COVID-19 vaccines targeted to currently circulating strains: an mRNA vaccine from Moderna (Spikevax) for those aged 6 months or older; an mRNA vaccine from Pfizer/BioNTech (Comirnaty) for those aged ≥ 5 years; and a protein subunit vaccine from Novavax (Nuvaxovid) for those aged ≥ 12 years. However, approvals restricting the scope of these approvals to certain high-risk groups, combined with the ACIP’s recent decision to not explicitly recommend them for any group, have complicated access for many patients.

Medical groups, including the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists (ACOG), have published their own recommendations (Table). Of note, in opposition to the FDA and ACIP, the AAP and AAFP strongly recommend routine vaccination for children aged 6 to 23 months because they have the highest risk for hospitalization. The AAFP and ACOG both recommend COVID-19 vaccination in pregnancy to protect the pregnant patient and provide passive antibody protection to their infants up to 6 months of age. The Vaccine Integrity Project’s review of 12 safety studies published since June 2024 found that mRNA vaccines were not associated with increases in any adverse maternal or infant outcomes and had a possible protective effect against preterm birth.

In my previous commentary, 70% of Medscape readers indicated that they would follow vaccination recommendations from AAP even if they differed from CDC guidance. Administering vaccines outside of FDA labeling indications (i.e., “off label”) typically requires a physician’s prescription, which will almost certainly reduce COVID-19 vaccine uptake in children and pregnant patients, given that most people received these shots in pharmacies during the 2024-25 season. CVS and Walgreens, the country’s two largest pharmacy chains, are requiring physician prescriptions or waiting for ACIP guidance to make the new vaccines available in many states. However, an increasing number of states have implemented executive orders or passed legislation to permit pharmacists to provide vaccines to anyone who wants them. For example, the Pennsylvania State Board of Pharmacy voted unanimously to issue guidance that would allow pharmacists to administer any vaccines recommended by AAFP, AAP, or ACOG.

Erosion of vaccine uptake could easily worsen the burden of illness for our patients and the health system. Navigating the unnecessarily complex landscape of COVID-19 vaccines will be challenging, but it remains worthwhile.
 

Kenneth W. Lin, MD, MPH, Associate Director, Department of Family Medicine, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: UpToDate; American Academy of Family Physicians; Archdiocese of Washington; Association of Prevention Teaching and Research.

A version of this article appeared on Medscape.com.

As a hospitalist, you are in a unique position to notice changes in your hospitalized patients. This frontline perspective can be used to improve inpatient attention and care, and differs from primary care, where a clinician might only see a patient once or twice a year, and subtle, gradual changes may be missed, said George Cao, MD, MBA, a hospitalist at the University of Vermont Medical Center in Burlington and assistant professor at UVM’s Larner College of Medicine. 

But in the hospital, Cao said even small shifts — like becoming less active, eating less, or changes in personality — can become much more obvious. 

“As hospitalists…we see patients throughout the day, in different situations, and often end up spending more time with them over the course of a week than their primary care provider might in a year,” Cao explained. “This gives us a real advantage in picking up on subtle changes in mental awareness.”

These assessments can also be evaluated with the benefit of daily labs, frequent bedside interactions, and 24–hour observations.

With older adults, Cao said it’s important to go beyond just what’s in the chart. 

“I always start by reviewing notes from the primary care provider and previous admissions, but some of the most valuable insights come from talking with family and close friends to get a true sense of the patient’s baseline — how they usually think, move, and interact,” he said.

 

Why to Watch for Declining Mental Awareness

Declining mental awareness in the inpatient setting is often a sign of an underlying problem — whether that’s a reversible medical condition, unrecognized dementia, or the development of delirium, Cao said.

“On the inpatient side, I pay close attention to more than just memory loss,” he said. 

Changes in how patients function day–to–day, shifts in their behavior, or even something as simple as not wanting to get out of bed can be early signs of an aging mind or untreated psychiatric issues, he noted. 

“Of course, we always rule out infections and medication side effects, but I also look for other reversible causes like thyroid problems, electrolyte imbalances, low oxygen, pain, urinary retention, constipation, and nutritional deficiencies,” Cao said.

Of note, delirium is the most common cause of sudden mental status changes in the hospital, and “it’s easy to miss if you’re not looking for it.”

He summarized that classic signs are an acute and fluctuating course with changes in alertness, but added there are other red flags too: disorientation, hallucinations, changes in sleep patterns, sporadic unsafe behaviors, mood swings, and changes in activity level, whether that’s agitation or just being unusually quiet. 

By combining what he notices bedside and what is learned from the medical record (and from the people who know the patient best), Cao said he’s able to catch these changes early, identify the underlying cause, and work toward the best possible outcome. 

“One of the main interventions is providing mental stimulation,” he said.

 

Why Mental Stimulation Is So Vital 

Mental stimulation of the patient is critical to recovery and may prevent prolonged illness, said Meghana R. Medavaram, MD, associate director of consultation liaison and emergency psychiatry at Montefiore Medical Center’s Weiler Hospital in New York City. “Keeping a patient active both physically and mentally can help prevent deconditioning and risks of prolonged immobility,” she said.

It’s important to note that when patients are out of their familiar routines, away from their usual environment and people, and their sleep is fragmented, this can make them even more vulnerable. Keeping patients mentally stimulated during their hospital stay can help maintain their attention, orientation, and a healthy sleep-wake cycle — all things that are easily thrown off in the hospital, Cao said. 

“These disruptions hit the pathways that control attention, wakefulness, and the sleep–wake cycle. That’s when you see attention drifting, orientation fading, and circadian rhythms unraveling, especially at night, which is why “sundowning” is so common, Cao said, referring to the syndrome where older adults or people with dementia experience behavioral changes in late afternoon or evening. “Mental stimulation is critical in the hospital because when the brain isn’t active and gets disoriented, it becomes an easy target for delirium.” 

He said delirium often develops in older adults when acute stressors like inflammation, low oxygen, metabolic imbalances, or sedating medications disrupt the brain’s arousal systems and networks, especially in older adults.

Therefore, Cao said, encourage your patients to be more engaged during the day through conversation, activities, or regular reorientation. “This supports the brain networks that help prevent inattention and confusion, which are the hallmarks of delirium. Daytime stimulation also helps build up the natural drive for nighttime sleep, so patients are less likely to nap during the day and be awake and disoriented at night.”

To support this, it’s helpful to schedule medications during waking hours instead of around–the–clock dosing that interrupts sleep, and to cluster nighttime care activities to minimize disturbances, Cao explained. Ensuring patients have their glasses, hearing aids, and familiar routines, along with encouraging mobility and hydration, further protects against delirium and supports patients’ cognitive health during hospitalization. “These same principles are just as important in outpatient subacute rehab settings and at home, so it’s essential to take home these strategies after discharge,” he said.

 

A Family Member or Friend May Help

Hospitalists can suggest straightforward ways to encourage families and friends to keep patients engaged during a hospital stay. Visits and chats can go a long way as conversations are incredibly grounding, Cao said. Other methods could be bringing in favorite foods or snacks, a phone chat or video call, or even showing prerecorded video messages. “These can be effective. Patients respond well to seeing and hearing familiar faces and voices, even if it’s just on a screen,” Cao said.

Beyond that, he said, activities such as watching and discussing the news, reading aloud, using tablets for games, watching movies, doing crossword puzzles, knitting, reminiscing, and playing word games can also be mentally stimulating for patients. 

In addition, safe exercises/activities that patients can do in bed — with advice from physical therapy and occupational therapy — are beneficial, Medavaram said. “These often include gentle range–of-motion activities,” she said. 

 

Share Importance of Mental Stimulation With Patients and Caregivers

If a hospitalist wants to motivate patients to keep their minds active, the framing should be simple, positive, and tied directly to their goals of getting better and getting home, said Medavaram. She provided this script suggestion:

“One of the best ways to help your recovery isn’t just taking your medicine, it’s keeping your mind active. When you’re in the hospital, it’s easy to spend the day lying in bed and staring at the TV in your room, but that can make your brain slow down and even cause confusion. Simple things — like reading, talking with visitors, doing puzzles, listening to music you enjoy, or telling a nurse about your favorite memories — can keep your brain sharp. Staying mentally active helps your thinking stay clear and can even help you get home sooner. Think of it like physical therapy for your brain.” 

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

As a hospitalist, you are in a unique position to notice changes in your hospitalized patients. This frontline perspective can be used to improve inpatient attention and care, and differs from primary care, where a clinician might only see a patient once or twice a year, and subtle, gradual changes may be missed, said George Cao, MD, MBA, a hospitalist at the University of Vermont Medical Center in Burlington and assistant professor at UVM’s Larner College of Medicine. 

But in the hospital, Cao said even small shifts — like becoming less active, eating less, or changes in personality — can become much more obvious. 

“As hospitalists…we see patients throughout the day, in different situations, and often end up spending more time with them over the course of a week than their primary care provider might in a year,” Cao explained. “This gives us a real advantage in picking up on subtle changes in mental awareness.”

These assessments can also be evaluated with the benefit of daily labs, frequent bedside interactions, and 24–hour observations.

With older adults, Cao said it’s important to go beyond just what’s in the chart. 

“I always start by reviewing notes from the primary care provider and previous admissions, but some of the most valuable insights come from talking with family and close friends to get a true sense of the patient’s baseline — how they usually think, move, and interact,” he said.

 

Why to Watch for Declining Mental Awareness

Declining mental awareness in the inpatient setting is often a sign of an underlying problem — whether that’s a reversible medical condition, unrecognized dementia, or the development of delirium, Cao said.

“On the inpatient side, I pay close attention to more than just memory loss,” he said. 

Changes in how patients function day–to–day, shifts in their behavior, or even something as simple as not wanting to get out of bed can be early signs of an aging mind or untreated psychiatric issues, he noted. 

“Of course, we always rule out infections and medication side effects, but I also look for other reversible causes like thyroid problems, electrolyte imbalances, low oxygen, pain, urinary retention, constipation, and nutritional deficiencies,” Cao said.

Of note, delirium is the most common cause of sudden mental status changes in the hospital, and “it’s easy to miss if you’re not looking for it.”

He summarized that classic signs are an acute and fluctuating course with changes in alertness, but added there are other red flags too: disorientation, hallucinations, changes in sleep patterns, sporadic unsafe behaviors, mood swings, and changes in activity level, whether that’s agitation or just being unusually quiet. 

By combining what he notices bedside and what is learned from the medical record (and from the people who know the patient best), Cao said he’s able to catch these changes early, identify the underlying cause, and work toward the best possible outcome. 

“One of the main interventions is providing mental stimulation,” he said.

 

Why Mental Stimulation Is So Vital 

Mental stimulation of the patient is critical to recovery and may prevent prolonged illness, said Meghana R. Medavaram, MD, associate director of consultation liaison and emergency psychiatry at Montefiore Medical Center’s Weiler Hospital in New York City. “Keeping a patient active both physically and mentally can help prevent deconditioning and risks of prolonged immobility,” she said.

It’s important to note that when patients are out of their familiar routines, away from their usual environment and people, and their sleep is fragmented, this can make them even more vulnerable. Keeping patients mentally stimulated during their hospital stay can help maintain their attention, orientation, and a healthy sleep-wake cycle — all things that are easily thrown off in the hospital, Cao said. 

“These disruptions hit the pathways that control attention, wakefulness, and the sleep–wake cycle. That’s when you see attention drifting, orientation fading, and circadian rhythms unraveling, especially at night, which is why “sundowning” is so common, Cao said, referring to the syndrome where older adults or people with dementia experience behavioral changes in late afternoon or evening. “Mental stimulation is critical in the hospital because when the brain isn’t active and gets disoriented, it becomes an easy target for delirium.” 

He said delirium often develops in older adults when acute stressors like inflammation, low oxygen, metabolic imbalances, or sedating medications disrupt the brain’s arousal systems and networks, especially in older adults.

Therefore, Cao said, encourage your patients to be more engaged during the day through conversation, activities, or regular reorientation. “This supports the brain networks that help prevent inattention and confusion, which are the hallmarks of delirium. Daytime stimulation also helps build up the natural drive for nighttime sleep, so patients are less likely to nap during the day and be awake and disoriented at night.”

To support this, it’s helpful to schedule medications during waking hours instead of around–the–clock dosing that interrupts sleep, and to cluster nighttime care activities to minimize disturbances, Cao explained. Ensuring patients have their glasses, hearing aids, and familiar routines, along with encouraging mobility and hydration, further protects against delirium and supports patients’ cognitive health during hospitalization. “These same principles are just as important in outpatient subacute rehab settings and at home, so it’s essential to take home these strategies after discharge,” he said.

 

A Family Member or Friend May Help

Hospitalists can suggest straightforward ways to encourage families and friends to keep patients engaged during a hospital stay. Visits and chats can go a long way as conversations are incredibly grounding, Cao said. Other methods could be bringing in favorite foods or snacks, a phone chat or video call, or even showing prerecorded video messages. “These can be effective. Patients respond well to seeing and hearing familiar faces and voices, even if it’s just on a screen,” Cao said.

Beyond that, he said, activities such as watching and discussing the news, reading aloud, using tablets for games, watching movies, doing crossword puzzles, knitting, reminiscing, and playing word games can also be mentally stimulating for patients. 

In addition, safe exercises/activities that patients can do in bed — with advice from physical therapy and occupational therapy — are beneficial, Medavaram said. “These often include gentle range–of-motion activities,” she said. 

 

Share Importance of Mental Stimulation With Patients and Caregivers

If a hospitalist wants to motivate patients to keep their minds active, the framing should be simple, positive, and tied directly to their goals of getting better and getting home, said Medavaram. She provided this script suggestion:

“One of the best ways to help your recovery isn’t just taking your medicine, it’s keeping your mind active. When you’re in the hospital, it’s easy to spend the day lying in bed and staring at the TV in your room, but that can make your brain slow down and even cause confusion. Simple things — like reading, talking with visitors, doing puzzles, listening to music you enjoy, or telling a nurse about your favorite memories — can keep your brain sharp. Staying mentally active helps your thinking stay clear and can even help you get home sooner. Think of it like physical therapy for your brain.” 

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

As a hospitalist, you are in a unique position to notice changes in your hospitalized patients. This frontline perspective can be used to improve inpatient attention and care, and differs from primary care, where a clinician might only see a patient once or twice a year, and subtle, gradual changes may be missed, said George Cao, MD, MBA, a hospitalist at the University of Vermont Medical Center in Burlington and assistant professor at UVM’s Larner College of Medicine. 

But in the hospital, Cao said even small shifts — like becoming less active, eating less, or changes in personality — can become much more obvious. 

“As hospitalists…we see patients throughout the day, in different situations, and often end up spending more time with them over the course of a week than their primary care provider might in a year,” Cao explained. “This gives us a real advantage in picking up on subtle changes in mental awareness.”

These assessments can also be evaluated with the benefit of daily labs, frequent bedside interactions, and 24–hour observations.

With older adults, Cao said it’s important to go beyond just what’s in the chart. 

“I always start by reviewing notes from the primary care provider and previous admissions, but some of the most valuable insights come from talking with family and close friends to get a true sense of the patient’s baseline — how they usually think, move, and interact,” he said.

 

Why to Watch for Declining Mental Awareness

Declining mental awareness in the inpatient setting is often a sign of an underlying problem — whether that’s a reversible medical condition, unrecognized dementia, or the development of delirium, Cao said.

“On the inpatient side, I pay close attention to more than just memory loss,” he said. 

Changes in how patients function day–to–day, shifts in their behavior, or even something as simple as not wanting to get out of bed can be early signs of an aging mind or untreated psychiatric issues, he noted. 

“Of course, we always rule out infections and medication side effects, but I also look for other reversible causes like thyroid problems, electrolyte imbalances, low oxygen, pain, urinary retention, constipation, and nutritional deficiencies,” Cao said.

Of note, delirium is the most common cause of sudden mental status changes in the hospital, and “it’s easy to miss if you’re not looking for it.”

He summarized that classic signs are an acute and fluctuating course with changes in alertness, but added there are other red flags too: disorientation, hallucinations, changes in sleep patterns, sporadic unsafe behaviors, mood swings, and changes in activity level, whether that’s agitation or just being unusually quiet. 

By combining what he notices bedside and what is learned from the medical record (and from the people who know the patient best), Cao said he’s able to catch these changes early, identify the underlying cause, and work toward the best possible outcome. 

“One of the main interventions is providing mental stimulation,” he said.

 

Why Mental Stimulation Is So Vital 

Mental stimulation of the patient is critical to recovery and may prevent prolonged illness, said Meghana R. Medavaram, MD, associate director of consultation liaison and emergency psychiatry at Montefiore Medical Center’s Weiler Hospital in New York City. “Keeping a patient active both physically and mentally can help prevent deconditioning and risks of prolonged immobility,” she said.

It’s important to note that when patients are out of their familiar routines, away from their usual environment and people, and their sleep is fragmented, this can make them even more vulnerable. Keeping patients mentally stimulated during their hospital stay can help maintain their attention, orientation, and a healthy sleep-wake cycle — all things that are easily thrown off in the hospital, Cao said. 

“These disruptions hit the pathways that control attention, wakefulness, and the sleep–wake cycle. That’s when you see attention drifting, orientation fading, and circadian rhythms unraveling, especially at night, which is why “sundowning” is so common, Cao said, referring to the syndrome where older adults or people with dementia experience behavioral changes in late afternoon or evening. “Mental stimulation is critical in the hospital because when the brain isn’t active and gets disoriented, it becomes an easy target for delirium.” 

He said delirium often develops in older adults when acute stressors like inflammation, low oxygen, metabolic imbalances, or sedating medications disrupt the brain’s arousal systems and networks, especially in older adults.

Therefore, Cao said, encourage your patients to be more engaged during the day through conversation, activities, or regular reorientation. “This supports the brain networks that help prevent inattention and confusion, which are the hallmarks of delirium. Daytime stimulation also helps build up the natural drive for nighttime sleep, so patients are less likely to nap during the day and be awake and disoriented at night.”

To support this, it’s helpful to schedule medications during waking hours instead of around–the–clock dosing that interrupts sleep, and to cluster nighttime care activities to minimize disturbances, Cao explained. Ensuring patients have their glasses, hearing aids, and familiar routines, along with encouraging mobility and hydration, further protects against delirium and supports patients’ cognitive health during hospitalization. “These same principles are just as important in outpatient subacute rehab settings and at home, so it’s essential to take home these strategies after discharge,” he said.

 

A Family Member or Friend May Help

Hospitalists can suggest straightforward ways to encourage families and friends to keep patients engaged during a hospital stay. Visits and chats can go a long way as conversations are incredibly grounding, Cao said. Other methods could be bringing in favorite foods or snacks, a phone chat or video call, or even showing prerecorded video messages. “These can be effective. Patients respond well to seeing and hearing familiar faces and voices, even if it’s just on a screen,” Cao said.

Beyond that, he said, activities such as watching and discussing the news, reading aloud, using tablets for games, watching movies, doing crossword puzzles, knitting, reminiscing, and playing word games can also be mentally stimulating for patients. 

In addition, safe exercises/activities that patients can do in bed — with advice from physical therapy and occupational therapy — are beneficial, Medavaram said. “These often include gentle range–of-motion activities,” she said. 

 

Share Importance of Mental Stimulation With Patients and Caregivers

If a hospitalist wants to motivate patients to keep their minds active, the framing should be simple, positive, and tied directly to their goals of getting better and getting home, said Medavaram. She provided this script suggestion:

“One of the best ways to help your recovery isn’t just taking your medicine, it’s keeping your mind active. When you’re in the hospital, it’s easy to spend the day lying in bed and staring at the TV in your room, but that can make your brain slow down and even cause confusion. Simple things — like reading, talking with visitors, doing puzzles, listening to music you enjoy, or telling a nurse about your favorite memories — can keep your brain sharp. Staying mentally active helps your thinking stay clear and can even help you get home sooner. Think of it like physical therapy for your brain.” 

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

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

Last month, I had the privilege of joining more than one hundred physician colleagues in Washington, DC, for AGA Advocacy Day. While standing amidst the majesty of the Capital, I found myself deeply appreciative for those who dedicate their time and energy to public service. Many of these dedicated federal workers choose to be in DC because of a sincere belief in their mission.

Among these mission-driven public servants are federal employees who work in the Department of Veterans Affairs (VA). As a member of this group, I come to work energized by the mission to care for those who have served in our military. In my clinical practice, I am reminded regularly of the sacrifices of veterans and their families. This month, and especially on Veterans Day, I hope we will take a moment to express gratitude to veterans for their service to our country.

This month is also a timely opportunity to recognize the immense contributions of VA physicians to the field of gastroenterology. Many young gastroenterologists may not know that it was the landmark VA Cooperative Study #380, led by Dr. David Lieberman (Portland VA) that helped push Medicare to cover reimbursement for screening colonoscopy. Today, one of the most important ongoing studies in our field – VA Cooperative Study #577 – continues the VA tradition of high-impact health services research. Launched in 2012, the study has enrolled 50,000 veterans to compare FIT and colonoscopy. It is led by Dr. Jason Dominitz (Seattle VA) and Dr. Doug Robertson (White River Junction VA). 

Beyond research, VA gastroenterologists play a critical role in training the next generation of clinicians. Over 700 gastroenterologists count the VA as a clinical home, making it the largest GI group practice in the country. Many of us — myself included — were trained or mentored by VA physicians whose dedication to service and science has shaped our careers and the field at large.

This month’s issue of GI & Hepatology News has stories about other important contributions to our field. The stories and perspective pieces on Artificial Intelligence are particularly poignant given the announcement last month on the awarding of the Nobel Prize in economics to researchers who study “creative destruction,” the way in which one technological innovation renders others obsolete. Perhaps this award offers another reason to reemphasize and embrace the “art” of medicine.

The views expressed here are my own and do not necessarily reflect the official policy or position of the U.S. Department of Veterans Affairs or the United States Government.

Ziad Gellad, MD, MPH, AGAF

Associate Editor

Last month, I had the privilege of joining more than one hundred physician colleagues in Washington, DC, for AGA Advocacy Day. While standing amidst the majesty of the Capital, I found myself deeply appreciative for those who dedicate their time and energy to public service. Many of these dedicated federal workers choose to be in DC because of a sincere belief in their mission.

Among these mission-driven public servants are federal employees who work in the Department of Veterans Affairs (VA). As a member of this group, I come to work energized by the mission to care for those who have served in our military. In my clinical practice, I am reminded regularly of the sacrifices of veterans and their families. This month, and especially on Veterans Day, I hope we will take a moment to express gratitude to veterans for their service to our country.

This month is also a timely opportunity to recognize the immense contributions of VA physicians to the field of gastroenterology. Many young gastroenterologists may not know that it was the landmark VA Cooperative Study #380, led by Dr. David Lieberman (Portland VA) that helped push Medicare to cover reimbursement for screening colonoscopy. Today, one of the most important ongoing studies in our field – VA Cooperative Study #577 – continues the VA tradition of high-impact health services research. Launched in 2012, the study has enrolled 50,000 veterans to compare FIT and colonoscopy. It is led by Dr. Jason Dominitz (Seattle VA) and Dr. Doug Robertson (White River Junction VA). 

Beyond research, VA gastroenterologists play a critical role in training the next generation of clinicians. Over 700 gastroenterologists count the VA as a clinical home, making it the largest GI group practice in the country. Many of us — myself included — were trained or mentored by VA physicians whose dedication to service and science has shaped our careers and the field at large.

This month’s issue of GI & Hepatology News has stories about other important contributions to our field. The stories and perspective pieces on Artificial Intelligence are particularly poignant given the announcement last month on the awarding of the Nobel Prize in economics to researchers who study “creative destruction,” the way in which one technological innovation renders others obsolete. Perhaps this award offers another reason to reemphasize and embrace the “art” of medicine.

The views expressed here are my own and do not necessarily reflect the official policy or position of the U.S. Department of Veterans Affairs or the United States Government.

Ziad Gellad, MD, MPH, AGAF

Associate Editor

Last month, I had the privilege of joining more than one hundred physician colleagues in Washington, DC, for AGA Advocacy Day. While standing amidst the majesty of the Capital, I found myself deeply appreciative for those who dedicate their time and energy to public service. Many of these dedicated federal workers choose to be in DC because of a sincere belief in their mission.

Among these mission-driven public servants are federal employees who work in the Department of Veterans Affairs (VA). As a member of this group, I come to work energized by the mission to care for those who have served in our military. In my clinical practice, I am reminded regularly of the sacrifices of veterans and their families. This month, and especially on Veterans Day, I hope we will take a moment to express gratitude to veterans for their service to our country.

This month is also a timely opportunity to recognize the immense contributions of VA physicians to the field of gastroenterology. Many young gastroenterologists may not know that it was the landmark VA Cooperative Study #380, led by Dr. David Lieberman (Portland VA) that helped push Medicare to cover reimbursement for screening colonoscopy. Today, one of the most important ongoing studies in our field – VA Cooperative Study #577 – continues the VA tradition of high-impact health services research. Launched in 2012, the study has enrolled 50,000 veterans to compare FIT and colonoscopy. It is led by Dr. Jason Dominitz (Seattle VA) and Dr. Doug Robertson (White River Junction VA). 

Beyond research, VA gastroenterologists play a critical role in training the next generation of clinicians. Over 700 gastroenterologists count the VA as a clinical home, making it the largest GI group practice in the country. Many of us — myself included — were trained or mentored by VA physicians whose dedication to service and science has shaped our careers and the field at large.

This month’s issue of GI & Hepatology News has stories about other important contributions to our field. The stories and perspective pieces on Artificial Intelligence are particularly poignant given the announcement last month on the awarding of the Nobel Prize in economics to researchers who study “creative destruction,” the way in which one technological innovation renders others obsolete. Perhaps this award offers another reason to reemphasize and embrace the “art” of medicine.

The views expressed here are my own and do not necessarily reflect the official policy or position of the U.S. Department of Veterans Affairs or the United States Government.

Ziad Gellad, MD, MPH, AGAF

Associate Editor

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

TOPLINE:

Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.

METHODOLOGY:

• Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
• The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
• Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
• They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.

TAKEAWAY:

• All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
• Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
• The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
• More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.

IN PRACTICE:

“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.

SOURCE:

The study was published online in PLOS Mental Health. 

LIMITATIONS:

The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.

DISCLOSURES:

The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.

METHODOLOGY:

• Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
• The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
• Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
• They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.

TAKEAWAY:

• All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
• Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
• The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
• More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.

IN PRACTICE:

“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.

SOURCE:

The study was published online in PLOS Mental Health. 

LIMITATIONS:

The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.

DISCLOSURES:

The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.

METHODOLOGY:

• Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
• The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
• Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
• They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.

TAKEAWAY:

• All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
• Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
• The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
• More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.

IN PRACTICE:

“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.

SOURCE:

The study was published online in PLOS Mental Health. 

LIMITATIONS:

The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.

DISCLOSURES:

The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.

METHODOLOGY:

• A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
• Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
• Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
• The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.

TAKEAWAY:

• During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
• Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
• The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
• The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.

IN PRACTICE:

“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.

SOURCE:

This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.

LIMITATIONS:

Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.

DISCLOSURES:

This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.

METHODOLOGY:

• A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
• Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
• Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
• The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.

TAKEAWAY:

• During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
• Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
• The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
• The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.

IN PRACTICE:

“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.

SOURCE:

This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.

LIMITATIONS:

Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.

DISCLOSURES:

This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.

METHODOLOGY:

• A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
• Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
• Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
• The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.

TAKEAWAY:

• During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
• Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
• The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
• The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.

IN PRACTICE:

“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.

SOURCE:

This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.

LIMITATIONS:

Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.

DISCLOSURES:

This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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