The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The drug maker Pfizer recently announced that vaccinated people are likely to need a booster shot to be effectively protected against new variants of COVID-19 and that the company would apply for Food and Drug Administration emergency use authorization for the shot. Top government health officials immediately and emphatically announced that the booster isn’t needed right now – and held firm to that position even after Pfizer’s top scientist made his case and shared preliminary data with them on July 12.

This has led to confusion. Should the nearly 60% of adult Americans who have been fully vaccinated seek out a booster or not? Is the protection that has allowed them to see loved ones and go out to dinner fading?

Ultimately, the question of whether a booster is needed is unlikely to determine the FDA’s decision. If recent history is predictive, booster shots will be here before long. That’s because of the outdated, 60-year-old basic standard the FDA uses to authorize medicines for sale: Is a new drug “safe and effective?”

The FDA, using that standard, will very likely have to authorize Pfizer’s booster for emergency use, as it did the company’s prior COVID shot. The booster is likely to be safe – hundreds of millions have taken the earlier shots – and Pfizer reported that it dramatically increases a vaccinated person’s antibodies against SARS-CoV-2. From that perspective, it may also be considered very effective.

But does that kind of efficacy matter? Is a higher level of antibodies needed to protect vaccinated Americans? Though antibody levels may wane some over time, the current vaccines deliver perfectly good immunity so far.

What if a booster is safe and effective in one sense but simply not needed – at least for now?

Reliance on the simple “safe and effective” standard – which certainly sounds reasonable – is a relic of a time when there were far fewer and simpler medicines available to treat diseases and before pharmaceutical manufacturing became one of the world’s biggest businesses.

The FDA’s 1938 landmark legislation focused primarily on safety after more than 100 Americans died from a raspberry-flavored liquid form of an early antibiotic because one of its ingredients was used as antifreeze. The 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act set out more specific requirements for drug approval: Companies must scientifically prove a drug’s effectiveness through “adequate and well-controlled studies.”

In today’s pharmaceutical universe, a simple “safe and effective” determination is not always an adequate bar, and it can be manipulated to sell drugs of questionable value. There’s also big money involved: Pfizer is already projecting $26 billion in COVID revenue in 2021.

The United States’ continued use of this standard to let drugs into the market has led to the approval of expensive, not necessarily very effective drugs. In 2014, for example, the FDA approved a toenail fungus drug that can cost up to $1,500 a month and that studies showed cured fewer than 10% of patients after a year of treatment. That’s more effective than doing nothing but less effective and more costly than a number of other treatments for this bothersome malady.

It has also led to a plethora of high-priced drugs to treat diseases like cancers, multiple sclerosis and type 2 diabetes that are all more effective than a placebo but have often not been tested very much against one another to determine which are most effective.

In today’s complex world, clarification is needed to determine just what kind of effectiveness the FDA should demand. And should that be the job of the FDA alone?

For example, should drugmakers prove a drug is significantly more effective than products already on the market? Or demonstrate cost-effectiveness – the health value of a product relative to its price – a metric used by Britain’s health system? And in which cases is effectiveness against a surrogate marker – like an antibody level – a good enough stand-in for whether a drug will have a significant impact on a patient’s health?

In most industrialized countries, broad access to the national market is a two-step process, said Aaron Kesselheim, a professor of medicine at Harvard Medical School, Boston, who studies drug development, marketing and law and recently served on an FDA advisory committee. The first part certifies that a drug is sufficiently safe and effective. That is immediately followed by an independent health technology assessment to see where it fits in the treatment armamentarium, including, in some countries, whether it is useful enough to be sold at all at the stated price. But there’s no such automatic process in the United States.

When Pfizer applies for authorization, the FDA may well clear a booster for the U.S. market. The Centers for Disease Control and Prevention, likely with advice from National Institutes of Health experts, will then have to decide whether to recommend it and for whom. This judgment call usually determines whether insurers will cover it. Pfizer is likely to profit handsomely from a government authorization, and the company will gain some revenue even if only the worried well, who can pay out of pocket, decide to get the shot.

To make any recommendation on a booster, government experts say they need more data. They could, for example, as Anthony S. Fauci, MD, has suggested, eventually green-light the additional vaccine shot only for a small group of patients at high risk for a deadly infection, such as the very old or transplant recipients who take immunosuppressant drugs, as some other countries have done.

But until the United States refines the FDA’s “safe and effective” standard or adds a second layer of vetting, when new products hit the market and manufacturers promote them, Americans will be left to decipher whose version of effective and necessary matters to them.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

After acute SARS-CoV-2 infection, patients report lingering malnutrition, loss of appetite, and failure to regain lost weight long after other gastrointestinal and non-GI symptoms have resolved, according to the results of a new study.

In the large, multicenter retrospective study published online in Clinical Gastroenterology and Hepatology, Anam Rizvi, MD, and colleagues at Long Island Jewish Medical Center, in New Hyde Park (N.Y.), report a high prevalence of GI symptoms among patients with COVID-19.

They followed 17,462 adult patients who were hospitalized for severe COVID-19 between March 2020 and January 2021. Of these, 3,229 (18.5%) also had GI symptoms.

The median age of the patients was 66 years, and 46.9% were women. The diverse population included White (46%), Black (23%), and Hispanic (17%) patients admitted to 12 medical centers of the Northwell Health System in Manhattan, Queens, Long Island, and Staten Island. The researchers followed patients for 3 months (88.7%) and 6 months (56.5%).

The most frequent initial GI symptoms were gastroenteritis (52.5%), malnutrition (23%), GI bleeding (20.4%), and idiopathic pancreatitis (0.5%). Notably, 50.6% of those with GI manifestations reported an inability to regain lost weight at 3 months; 32.4% reported failure to regain lost weight at 6 months.

These percentages rose among patients with malnutrition, as determined by a board-certified in-hospital nutritionist; 56.4% failed to gain weight at 6 months. A median 14.7-lb weight loss persisted at the half-year mark.

In contrast to these lingering symptoms, gastroenteritis, GI bleeding, and pancreatitis all resolved by 3 months post hospitalization.

“We were somewhat shocked that the prevalence of these symptoms was so high, but it’s overall reassuring that most GI symptoms of COVID-19 resolve,” study author Arvind J. Trindade, MD, told this news organization. “In some COVID patients, we’re seeing an inability to gain weight without diarrhea or postinfectious irritable bowel syndrome.

“Patients with an inability to regain weight should consider follow-up with a nutritionist,” continued Dr. Trindade, who is the center’s director of endoscopy and an associate professor at the Feinstein Institutes for Medical Research, in Manhasset (N.Y.). His group also recommends developing malnutrition screening assessments for COVID-19 patients who recover from the acute infection.

The study was prompted by clinical observations during follow-up.

“We saw that a lot of these patients had trouble regaining weight, but we still don’t know why,” Dr. Trindade said. There were no discriminating clinical features apart from malnutrition that indicated an increased risk, and no socioeconomic or demographic characteristics. “We also looked at whether any factors predicted malnutrition, and there weren’t any that would predispose to malnutrition,” he added.

“We’re now reaching out to nonclinical investigators to see if there’s an interest in studying the underlying science behind these symptoms,” Dr. Trindade said.

His group plans to release 12-month follow-up data from the second wave of the pandemic in January 2022.

Initial GI symptoms are thought to be due to the virus’s S1 spike protein’s binding to the angiotensin-converting enzyme 2 receptors, which are abundant in GI epithelial cells. “But why patients have long-term GI sequelae is probably a whole different physiological mechanism,” Dr. Trindade said. “The thought is that there has to be some hormone or pathway that doesn’t allow them to regain weight.”

“The hospital cohort by [Dr. Rizvi] and colleagues is unique and helpful in that patients with GI symptoms are less likely to be hospitalized, and perhaps those patients who are sick enough for admission to the hospital who also have GI symptoms need specific attention paid to their appetite, weight, and nutritional status,” said Jordan M. Shapiro, MD, who commented on the study but was not involved in it.

The constellations of GI symptoms are difficult to distinguish from other postinfectious GI syndromes, such as irritable bowel syndrome and gastroparesis, added Dr. Shapiro, an assistant professor of medicine in gastroenterology and hepatology at Baylor College of Medicine, Houston. “We’re still unpacking what is and is not specific to post–COVID-19 GI symptoms. Prospective studies are necessary to further study this phenomenon.”

Last year, a small Italian study documented significant weight loss and malnutrition in a hospital cohort of 213 discharged COVID-19 patients. In that study, the duration of disease was predictive of weight loss.

The authors note several study limitations, including that the cohort was limited to hospitalized patients from New York and that the 6-month follow-up period was short.

The study received no funding. Dr. Trindade serves as a consultant to Pentax Medical. All other authors and Dr. Shapiro have disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

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

After acute SARS-CoV-2 infection, patients report lingering malnutrition, loss of appetite, and failure to regain lost weight long after other gastrointestinal and non-GI symptoms have resolved, according to the results of a new study.

In the large, multicenter retrospective study published online in Clinical Gastroenterology and Hepatology, Anam Rizvi, MD, and colleagues at Long Island Jewish Medical Center, in New Hyde Park (N.Y.), report a high prevalence of GI symptoms among patients with COVID-19.

They followed 17,462 adult patients who were hospitalized for severe COVID-19 between March 2020 and January 2021. Of these, 3,229 (18.5%) also had GI symptoms.

The median age of the patients was 66 years, and 46.9% were women. The diverse population included White (46%), Black (23%), and Hispanic (17%) patients admitted to 12 medical centers of the Northwell Health System in Manhattan, Queens, Long Island, and Staten Island. The researchers followed patients for 3 months (88.7%) and 6 months (56.5%).

The most frequent initial GI symptoms were gastroenteritis (52.5%), malnutrition (23%), GI bleeding (20.4%), and idiopathic pancreatitis (0.5%). Notably, 50.6% of those with GI manifestations reported an inability to regain lost weight at 3 months; 32.4% reported failure to regain lost weight at 6 months.

These percentages rose among patients with malnutrition, as determined by a board-certified in-hospital nutritionist; 56.4% failed to gain weight at 6 months. A median 14.7-lb weight loss persisted at the half-year mark.

In contrast to these lingering symptoms, gastroenteritis, GI bleeding, and pancreatitis all resolved by 3 months post hospitalization.

“We were somewhat shocked that the prevalence of these symptoms was so high, but it’s overall reassuring that most GI symptoms of COVID-19 resolve,” study author Arvind J. Trindade, MD, told this news organization. “In some COVID patients, we’re seeing an inability to gain weight without diarrhea or postinfectious irritable bowel syndrome.

“Patients with an inability to regain weight should consider follow-up with a nutritionist,” continued Dr. Trindade, who is the center’s director of endoscopy and an associate professor at the Feinstein Institutes for Medical Research, in Manhasset (N.Y.). His group also recommends developing malnutrition screening assessments for COVID-19 patients who recover from the acute infection.

The study was prompted by clinical observations during follow-up.

“We saw that a lot of these patients had trouble regaining weight, but we still don’t know why,” Dr. Trindade said. There were no discriminating clinical features apart from malnutrition that indicated an increased risk, and no socioeconomic or demographic characteristics. “We also looked at whether any factors predicted malnutrition, and there weren’t any that would predispose to malnutrition,” he added.

“We’re now reaching out to nonclinical investigators to see if there’s an interest in studying the underlying science behind these symptoms,” Dr. Trindade said.

His group plans to release 12-month follow-up data from the second wave of the pandemic in January 2022.

Initial GI symptoms are thought to be due to the virus’s S1 spike protein’s binding to the angiotensin-converting enzyme 2 receptors, which are abundant in GI epithelial cells. “But why patients have long-term GI sequelae is probably a whole different physiological mechanism,” Dr. Trindade said. “The thought is that there has to be some hormone or pathway that doesn’t allow them to regain weight.”

“The hospital cohort by [Dr. Rizvi] and colleagues is unique and helpful in that patients with GI symptoms are less likely to be hospitalized, and perhaps those patients who are sick enough for admission to the hospital who also have GI symptoms need specific attention paid to their appetite, weight, and nutritional status,” said Jordan M. Shapiro, MD, who commented on the study but was not involved in it.

The constellations of GI symptoms are difficult to distinguish from other postinfectious GI syndromes, such as irritable bowel syndrome and gastroparesis, added Dr. Shapiro, an assistant professor of medicine in gastroenterology and hepatology at Baylor College of Medicine, Houston. “We’re still unpacking what is and is not specific to post–COVID-19 GI symptoms. Prospective studies are necessary to further study this phenomenon.”

Last year, a small Italian study documented significant weight loss and malnutrition in a hospital cohort of 213 discharged COVID-19 patients. In that study, the duration of disease was predictive of weight loss.

The authors note several study limitations, including that the cohort was limited to hospitalized patients from New York and that the 6-month follow-up period was short.

The study received no funding. Dr. Trindade serves as a consultant to Pentax Medical. All other authors and Dr. Shapiro have disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

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

After acute SARS-CoV-2 infection, patients report lingering malnutrition, loss of appetite, and failure to regain lost weight long after other gastrointestinal and non-GI symptoms have resolved, according to the results of a new study.

In the large, multicenter retrospective study published online in Clinical Gastroenterology and Hepatology, Anam Rizvi, MD, and colleagues at Long Island Jewish Medical Center, in New Hyde Park (N.Y.), report a high prevalence of GI symptoms among patients with COVID-19.

They followed 17,462 adult patients who were hospitalized for severe COVID-19 between March 2020 and January 2021. Of these, 3,229 (18.5%) also had GI symptoms.

The median age of the patients was 66 years, and 46.9% were women. The diverse population included White (46%), Black (23%), and Hispanic (17%) patients admitted to 12 medical centers of the Northwell Health System in Manhattan, Queens, Long Island, and Staten Island. The researchers followed patients for 3 months (88.7%) and 6 months (56.5%).

The most frequent initial GI symptoms were gastroenteritis (52.5%), malnutrition (23%), GI bleeding (20.4%), and idiopathic pancreatitis (0.5%). Notably, 50.6% of those with GI manifestations reported an inability to regain lost weight at 3 months; 32.4% reported failure to regain lost weight at 6 months.

These percentages rose among patients with malnutrition, as determined by a board-certified in-hospital nutritionist; 56.4% failed to gain weight at 6 months. A median 14.7-lb weight loss persisted at the half-year mark.

In contrast to these lingering symptoms, gastroenteritis, GI bleeding, and pancreatitis all resolved by 3 months post hospitalization.

“We were somewhat shocked that the prevalence of these symptoms was so high, but it’s overall reassuring that most GI symptoms of COVID-19 resolve,” study author Arvind J. Trindade, MD, told this news organization. “In some COVID patients, we’re seeing an inability to gain weight without diarrhea or postinfectious irritable bowel syndrome.

“Patients with an inability to regain weight should consider follow-up with a nutritionist,” continued Dr. Trindade, who is the center’s director of endoscopy and an associate professor at the Feinstein Institutes for Medical Research, in Manhasset (N.Y.). His group also recommends developing malnutrition screening assessments for COVID-19 patients who recover from the acute infection.

The study was prompted by clinical observations during follow-up.

“We saw that a lot of these patients had trouble regaining weight, but we still don’t know why,” Dr. Trindade said. There were no discriminating clinical features apart from malnutrition that indicated an increased risk, and no socioeconomic or demographic characteristics. “We also looked at whether any factors predicted malnutrition, and there weren’t any that would predispose to malnutrition,” he added.

“We’re now reaching out to nonclinical investigators to see if there’s an interest in studying the underlying science behind these symptoms,” Dr. Trindade said.

His group plans to release 12-month follow-up data from the second wave of the pandemic in January 2022.

Initial GI symptoms are thought to be due to the virus’s S1 spike protein’s binding to the angiotensin-converting enzyme 2 receptors, which are abundant in GI epithelial cells. “But why patients have long-term GI sequelae is probably a whole different physiological mechanism,” Dr. Trindade said. “The thought is that there has to be some hormone or pathway that doesn’t allow them to regain weight.”

“The hospital cohort by [Dr. Rizvi] and colleagues is unique and helpful in that patients with GI symptoms are less likely to be hospitalized, and perhaps those patients who are sick enough for admission to the hospital who also have GI symptoms need specific attention paid to their appetite, weight, and nutritional status,” said Jordan M. Shapiro, MD, who commented on the study but was not involved in it.

The constellations of GI symptoms are difficult to distinguish from other postinfectious GI syndromes, such as irritable bowel syndrome and gastroparesis, added Dr. Shapiro, an assistant professor of medicine in gastroenterology and hepatology at Baylor College of Medicine, Houston. “We’re still unpacking what is and is not specific to post–COVID-19 GI symptoms. Prospective studies are necessary to further study this phenomenon.”

Last year, a small Italian study documented significant weight loss and malnutrition in a hospital cohort of 213 discharged COVID-19 patients. In that study, the duration of disease was predictive of weight loss.

The authors note several study limitations, including that the cohort was limited to hospitalized patients from New York and that the 6-month follow-up period was short.

The study received no funding. Dr. Trindade serves as a consultant to Pentax Medical. All other authors and Dr. Shapiro have disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

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

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

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

In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.

“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”

His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.

The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).

As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while blistering lesions could suggest a fixed drug response or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.

What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”

The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”

In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.

“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”

Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”

As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).

Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”

Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.

[email protected]

In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.

“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”

His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.

The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).

As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while blistering lesions could suggest a fixed drug response or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.

What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”

The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”

In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.

“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”

Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”

As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).

Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”

Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.

[email protected]

In the opinion of Neil H. Shear, MD, a stepwise approach is the best way to diagnose possible drug-induced skin disease and determine the root cause.

“Often, we need to think of more than one cause,” he said during the annual meeting of the Society for Pediatric Dermatology. “It could be drug X. It could be drug Y. It could be contrast media. We must think broadly and pay special attention to skin of color, overlapping syndromes, and the changing diagnostic assessment over time.”

His suggested diagnostic triangle includes appearance of the rash or lesion(s), systemic impact, and histology. “The first is the appearance,” said Dr. Shear, professor emeritus of dermatology, clinical pharmacology and toxicology, and medicine at the University of Toronto. “Is it exanthem? Is it blistering? Don’t just say drug ‘rash.’ That doesn’t work. You need to know if there are systemic features, and sometimes histologic information can change your approach or diagnosis, but not as often as one might think,” he said, noting that, in his view, the two main factors are appearance and systemic impact.

The presence of fever is a hallmark of systemic problems, he continued, “so if you see fever, you know you’re probably going to be dealing with a complex reaction, so we need to know the morphology.” Consider whether it is simple exanthem (a mild, uncomplicated rash) or complex exanthem (drug rash with eosinophilia and systemic symptoms or fever, malaise, and adenopathy).

As for other morphologies, urticarial lesions could be urticaria or a serum sickness-like reaction, pustular lesions could be acneiform or acute generalized exanthematous pustulosis, while blistering lesions could suggest a fixed drug response or Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Dr. Shear considers SJS/TEN as a spectrum of blistering disease, “because there’s not a single diagnosis,” he said. “There’s a spectrum, if you will, depending on how advanced people are in their disease.” He coauthored a 1991 report describing eight cases of mycoplasma and Stevens-Johnson syndrome. “I was surprised at how long that stood up as about the only paper in that area,” he said. “But there’s much more happening now with a proliferation of terms,” he added, referring to MIRM (Mycoplasma pneumonia–induced rash and mucositis), RIME (reactive infectious mucocutaneous eruption); and Fuchs syndrome, or SJS without skin lesions.

What was not appreciated in the early classification of SJS, he continued, was a “side basket” of bullous erythema multiforme. “We didn’t know what to call it,” he said. “At one point we called it bullous erythema multiforme. At another point we called it erythema multiforme major. We just didn’t know what it was.”

The appearance and systemic effects of SJS comprise what he termed SJS type 2 – or the early stages of TEN. Taken together, he refers to these two conditions as TEN Spectrum, or TENS. “One of the traps is that TENS can look like varicella, and vice versa, especially in very dark brown or black skin,” Dr. Shear said. “You have to be careful. A biopsy might be worthwhile. Acute lupus has the pathology of TENS but the patients are not as systemically ill as true TENS.”

In 2011, Japanese researchers reported on 38 cases of SJS associated with M. pneumoniae, and 78 cases of drug-induced SJS. They found that 66% of adult patients with M. pneumoniae–associated SJS developed mucocutaneous lesions and fever/respiratory symptoms on the same day, mostly shortness of breath and cough. In contrast, most of the patients aged under 20 years developed fever/respiratory symptoms before mucocutaneous involvement.

“The big clinical differentiator between drug-induced SJS and mycoplasma-induced SJS was respiratory disorder,” said Dr. Shear, who was not affiliated with the study. “That means you’re probably looking at something that’s mycoplasma related [when respiratory problems are present]. Even if you can’t prove it’s mycoplasma related, that probably needs to be the target of your therapy. The idea ... is to make sure it’s clear at the end. One, so they get better, and two, so that we’re not giving drugs needlessly when it was really mycoplasma.”

Noting that HLA-B*15:02 is a marker for carbamazepine-induced SJS and TEN, he said, “a positive HLA test can support the diagnosis, confirm the suspected offending drug, and is valuable for familial genetic counseling.”

As for treatment of SJS, TEN, and other cytotoxic T-lymphocyte–mediated severe cutaneous adverse reactions, a randomized Japanese clinical trial evaluating prednisolone 1-1.5 mg/kg/day IV versus etanercept 25-50 mg subcutaneously twice per week in 96 patients with SJS-TEN found that etanercept decreased the mortality rate by 8.3%. In addition, etanercept reduced skin healing time, when compared with prednisolone (a median of 14 vs. 19 days, respectively; P = .010), and was associated with a lower incidence of GI hemorrhage (2.6% vs. 18.2%, respectively; P = .03).

Dr. Shear said that he would like to see better therapeutics for severe, complex patients. “After leaving the hospital, people with SJS or people with TEN need to have ongoing care, consultation, and explanation so they and their families know what drugs are safe in the future.”

Dr. Shear disclosed that he has been a consultant to AbbVie, Amgen, Bausch Medicine, Novartis, Sanofi-Genzyme, UCB, LEO Pharma, Otsuka, Janssen, Alpha Laboratories, Lilly, ChemoCentryx, Vivoryon, Galderma, Innovaderm, Chromocell, and Kyowa Kirin.

[email protected]

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Five of the more uncommon dermatologic disorders – sarcoidosis, Rosai-Dorfman disease, Erdheim-Chester disease, eosinophilic fasciitis, and cutaneous Crohn disease – are linked to internal diseases and may spawn misdiagnoses, a dermatologist told colleagues.

“Proper diagnosis can lead to an effective management in our patients,” said Jeffrey Callen, MD, professor of medicine and chief of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease.
 

Sarcoidosis

The cause of sarcoidosis, an inflammatory disease that tends to affect the lungs, “is unknown, but it’s probably an immunologic disorder,” Dr. Callen said, “and there probably is a genetic predisposition.” About 20%-25% of patients with sarcoidosis have skin lesions that are either “specific” (a biopsy that reveals a noncaseating – “naked” – granuloma) or “nonspecific” (most commonly, erythema nodosum, or EN).

The specific lesions in sarcoidosis may occur in parts of the body, such as the knees, which were injured earlier in life and may have taken in foreign bodies, Dr. Callen said. As for nonspecific lesions, about 20% of patients with EN have an acute, self-limiting form of sarcoidosis. “These patients will have bilateral hilar lymphadenopathy, anterior uveitis, and polyarthritis. It’s generally treated symptomatically because it goes away on its own.”

He cautioned colleagues to beware of indurated, infiltrative facial lesions known as lupus pernio that are commonly found on the nose. They’re more prevalent in Black patients and possibly women, who are at higher risk of manifestations outside the skin, he said. “If you have it along the nasal rim, you should look into the upper respiratory tract for involvement.”

Dr. Callen recommends an extensive workup in patients with suspected sarcoidosis, including biopsy (with the exception of EN lesions), cultures and special stains, and screening when appropriate, for disease in organs such as the eyes, lungs, heart, and kidneys.

As for treatment, “the disease is in the dermis, and some topical therapies are not highly effective,” he said. There are injections that can be given, including corticosteroids, and there are a variety of oral treatments that are all off label.” These include corticosteroids, antimalarials, allopurinol, and tetracyclines, among several others. Subcutaneous and intravenous treatments are also options, along with surgery and laser therapy to treat specific lesions.

Rosai-Dorfman disease

This rare disorder is caused by overproduction of certain white blood cells in the lymph nodes, which can cause nodular lesions. The disease most often appears in children and young adults, often Black individuals and males. It is fatal in as many as 11% of patients, justifying aggressive treatment in patients with aggressive disease, Dr. Callen said. When it’s limited to the skin, however, “nothing may need to be done.”

Dr. Callen highlighted consensus recommendations about diagnosis and treatment of Rosai-Dorfman disease published in 2018.

He also noted the existence of cutaneous Rosai-Dorfman disease, a “solitary process” that appears more commonly in females, and in people of Asian heritage, compared with White individuals. It is characterized by single, clustered or widespread lesions: They can be xanthomatous, erythematous, or red-brown papules, nodules, and plaques. They’re acneiform, pustular, giant granuloma annulare–like, subcutaneous, and vasculitis-like, he said.

While Rosai-Dorfman disease can be linked to lymphoma, hypothyroidism, and lupus erythematosus, “nothing necessarily needs to be done when it’s skin-limited since it can be self-resolving,” he noted. Other treatments include radiotherapy, cryotherapy, excision, topical and oral corticosteroids, thalidomide, and methotrexate.

The disease can be serious, and is fatal in 5% of cases. When a vital organ is threatened, Dr. Callen suggested surgery, chemotherapy, or radiation.
 

Erdheim-Chester disease

This disease – which is extremely rare, with just 500 cases noted before 2014 – occurs when the body overproduces macrophages. It’s most common in middle-aged people and in men, who make up 75% of cases. About a quarter of patients develop skin lesions: Red-brown to yellow nodules and xanthelasma-like indurated plaques on the eyelids, scalp, neck, trunk, and axillae, and “other cutaneous manifestations have been reported in patients,” Dr. Callen said.

The disease also frequently affects the bones, large vessels, heart, lungs, and central nervous system. Interferon-alpha is the first-line treatment, and there are several other alternative therapies, although 5-year survival (68%) is poor, and it is especially likely to be fatal in those with central nervous system involvement.
 

Eosinophilic fasciitis

Eosinophilic fasciitis (EF) “is a disorder of unknown etiology that causes sclerosis of the skin” without Raynaud’s phenomenon, Dr. Callen said. Look for erythema, swelling, and induration of the extremities that is accompanied by peripheral eosinophilia, and if necessary, confirm the diagnosis with full skin-to-muscle biopsy or MRI.

There are many possible triggers, including strenuous exercise, initiation with hemodialysis, radiation therapy and burns, and graft-versus-host disease. Other potential causes include exposure to medications such as statins, phenytoin, ramipril, subcutaneous heparin, and immune checkpoint inhibitor therapy. The disorder is also linked to autoimmune and hematologic disorders.

Dr. Callen, who highlighted EF guidelines published in 2018, said treatments include physical therapy, prednisone, methotrexate, mycophenolate, and hydroxychloroquine.
 

Metastatic Crohn’s disease

This is a rare granulomatous inflammation of skin that often affects the genitals, especially in children. It is noncontiguous with the GI tract, and severity of skin involvement does not always parallel the severity of the disease in the GI tract, Dr. Callen said. However, the condition can occur before or simultaneously with the development of GI disease, or after GI surgery.

He highlighted a review of metastatic Crohn’s disease, published in 2014, and noted that there are multiple treatments, including systemic corticosteroids, tumor necrosis factor–alpha inhibitors, and topical therapies.

Dr. Callen reported no relevant disclosures.

Five of the more uncommon dermatologic disorders – sarcoidosis, Rosai-Dorfman disease, Erdheim-Chester disease, eosinophilic fasciitis, and cutaneous Crohn disease – are linked to internal diseases and may spawn misdiagnoses, a dermatologist told colleagues.

“Proper diagnosis can lead to an effective management in our patients,” said Jeffrey Callen, MD, professor of medicine and chief of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease.
 

Sarcoidosis

The cause of sarcoidosis, an inflammatory disease that tends to affect the lungs, “is unknown, but it’s probably an immunologic disorder,” Dr. Callen said, “and there probably is a genetic predisposition.” About 20%-25% of patients with sarcoidosis have skin lesions that are either “specific” (a biopsy that reveals a noncaseating – “naked” – granuloma) or “nonspecific” (most commonly, erythema nodosum, or EN).

The specific lesions in sarcoidosis may occur in parts of the body, such as the knees, which were injured earlier in life and may have taken in foreign bodies, Dr. Callen said. As for nonspecific lesions, about 20% of patients with EN have an acute, self-limiting form of sarcoidosis. “These patients will have bilateral hilar lymphadenopathy, anterior uveitis, and polyarthritis. It’s generally treated symptomatically because it goes away on its own.”

He cautioned colleagues to beware of indurated, infiltrative facial lesions known as lupus pernio that are commonly found on the nose. They’re more prevalent in Black patients and possibly women, who are at higher risk of manifestations outside the skin, he said. “If you have it along the nasal rim, you should look into the upper respiratory tract for involvement.”

Dr. Callen recommends an extensive workup in patients with suspected sarcoidosis, including biopsy (with the exception of EN lesions), cultures and special stains, and screening when appropriate, for disease in organs such as the eyes, lungs, heart, and kidneys.

As for treatment, “the disease is in the dermis, and some topical therapies are not highly effective,” he said. There are injections that can be given, including corticosteroids, and there are a variety of oral treatments that are all off label.” These include corticosteroids, antimalarials, allopurinol, and tetracyclines, among several others. Subcutaneous and intravenous treatments are also options, along with surgery and laser therapy to treat specific lesions.

Rosai-Dorfman disease

This rare disorder is caused by overproduction of certain white blood cells in the lymph nodes, which can cause nodular lesions. The disease most often appears in children and young adults, often Black individuals and males. It is fatal in as many as 11% of patients, justifying aggressive treatment in patients with aggressive disease, Dr. Callen said. When it’s limited to the skin, however, “nothing may need to be done.”

Dr. Callen highlighted consensus recommendations about diagnosis and treatment of Rosai-Dorfman disease published in 2018.

He also noted the existence of cutaneous Rosai-Dorfman disease, a “solitary process” that appears more commonly in females, and in people of Asian heritage, compared with White individuals. It is characterized by single, clustered or widespread lesions: They can be xanthomatous, erythematous, or red-brown papules, nodules, and plaques. They’re acneiform, pustular, giant granuloma annulare–like, subcutaneous, and vasculitis-like, he said.

While Rosai-Dorfman disease can be linked to lymphoma, hypothyroidism, and lupus erythematosus, “nothing necessarily needs to be done when it’s skin-limited since it can be self-resolving,” he noted. Other treatments include radiotherapy, cryotherapy, excision, topical and oral corticosteroids, thalidomide, and methotrexate.

The disease can be serious, and is fatal in 5% of cases. When a vital organ is threatened, Dr. Callen suggested surgery, chemotherapy, or radiation.
 

Erdheim-Chester disease

This disease – which is extremely rare, with just 500 cases noted before 2014 – occurs when the body overproduces macrophages. It’s most common in middle-aged people and in men, who make up 75% of cases. About a quarter of patients develop skin lesions: Red-brown to yellow nodules and xanthelasma-like indurated plaques on the eyelids, scalp, neck, trunk, and axillae, and “other cutaneous manifestations have been reported in patients,” Dr. Callen said.

The disease also frequently affects the bones, large vessels, heart, lungs, and central nervous system. Interferon-alpha is the first-line treatment, and there are several other alternative therapies, although 5-year survival (68%) is poor, and it is especially likely to be fatal in those with central nervous system involvement.
 

Eosinophilic fasciitis

Eosinophilic fasciitis (EF) “is a disorder of unknown etiology that causes sclerosis of the skin” without Raynaud’s phenomenon, Dr. Callen said. Look for erythema, swelling, and induration of the extremities that is accompanied by peripheral eosinophilia, and if necessary, confirm the diagnosis with full skin-to-muscle biopsy or MRI.

There are many possible triggers, including strenuous exercise, initiation with hemodialysis, radiation therapy and burns, and graft-versus-host disease. Other potential causes include exposure to medications such as statins, phenytoin, ramipril, subcutaneous heparin, and immune checkpoint inhibitor therapy. The disorder is also linked to autoimmune and hematologic disorders.

Dr. Callen, who highlighted EF guidelines published in 2018, said treatments include physical therapy, prednisone, methotrexate, mycophenolate, and hydroxychloroquine.
 

Metastatic Crohn’s disease

This is a rare granulomatous inflammation of skin that often affects the genitals, especially in children. It is noncontiguous with the GI tract, and severity of skin involvement does not always parallel the severity of the disease in the GI tract, Dr. Callen said. However, the condition can occur before or simultaneously with the development of GI disease, or after GI surgery.

He highlighted a review of metastatic Crohn’s disease, published in 2014, and noted that there are multiple treatments, including systemic corticosteroids, tumor necrosis factor–alpha inhibitors, and topical therapies.

Dr. Callen reported no relevant disclosures.

Five of the more uncommon dermatologic disorders – sarcoidosis, Rosai-Dorfman disease, Erdheim-Chester disease, eosinophilic fasciitis, and cutaneous Crohn disease – are linked to internal diseases and may spawn misdiagnoses, a dermatologist told colleagues.

“Proper diagnosis can lead to an effective management in our patients,” said Jeffrey Callen, MD, professor of medicine and chief of dermatology at the University of Louisville (Ky.), who spoke at the Inaugural Symposium for Inflammatory Skin Disease.
 

Sarcoidosis

The cause of sarcoidosis, an inflammatory disease that tends to affect the lungs, “is unknown, but it’s probably an immunologic disorder,” Dr. Callen said, “and there probably is a genetic predisposition.” About 20%-25% of patients with sarcoidosis have skin lesions that are either “specific” (a biopsy that reveals a noncaseating – “naked” – granuloma) or “nonspecific” (most commonly, erythema nodosum, or EN).

The specific lesions in sarcoidosis may occur in parts of the body, such as the knees, which were injured earlier in life and may have taken in foreign bodies, Dr. Callen said. As for nonspecific lesions, about 20% of patients with EN have an acute, self-limiting form of sarcoidosis. “These patients will have bilateral hilar lymphadenopathy, anterior uveitis, and polyarthritis. It’s generally treated symptomatically because it goes away on its own.”

He cautioned colleagues to beware of indurated, infiltrative facial lesions known as lupus pernio that are commonly found on the nose. They’re more prevalent in Black patients and possibly women, who are at higher risk of manifestations outside the skin, he said. “If you have it along the nasal rim, you should look into the upper respiratory tract for involvement.”

Dr. Callen recommends an extensive workup in patients with suspected sarcoidosis, including biopsy (with the exception of EN lesions), cultures and special stains, and screening when appropriate, for disease in organs such as the eyes, lungs, heart, and kidneys.

As for treatment, “the disease is in the dermis, and some topical therapies are not highly effective,” he said. There are injections that can be given, including corticosteroids, and there are a variety of oral treatments that are all off label.” These include corticosteroids, antimalarials, allopurinol, and tetracyclines, among several others. Subcutaneous and intravenous treatments are also options, along with surgery and laser therapy to treat specific lesions.

Rosai-Dorfman disease

This rare disorder is caused by overproduction of certain white blood cells in the lymph nodes, which can cause nodular lesions. The disease most often appears in children and young adults, often Black individuals and males. It is fatal in as many as 11% of patients, justifying aggressive treatment in patients with aggressive disease, Dr. Callen said. When it’s limited to the skin, however, “nothing may need to be done.”

Dr. Callen highlighted consensus recommendations about diagnosis and treatment of Rosai-Dorfman disease published in 2018.

He also noted the existence of cutaneous Rosai-Dorfman disease, a “solitary process” that appears more commonly in females, and in people of Asian heritage, compared with White individuals. It is characterized by single, clustered or widespread lesions: They can be xanthomatous, erythematous, or red-brown papules, nodules, and plaques. They’re acneiform, pustular, giant granuloma annulare–like, subcutaneous, and vasculitis-like, he said.

While Rosai-Dorfman disease can be linked to lymphoma, hypothyroidism, and lupus erythematosus, “nothing necessarily needs to be done when it’s skin-limited since it can be self-resolving,” he noted. Other treatments include radiotherapy, cryotherapy, excision, topical and oral corticosteroids, thalidomide, and methotrexate.

The disease can be serious, and is fatal in 5% of cases. When a vital organ is threatened, Dr. Callen suggested surgery, chemotherapy, or radiation.
 

Erdheim-Chester disease

This disease – which is extremely rare, with just 500 cases noted before 2014 – occurs when the body overproduces macrophages. It’s most common in middle-aged people and in men, who make up 75% of cases. About a quarter of patients develop skin lesions: Red-brown to yellow nodules and xanthelasma-like indurated plaques on the eyelids, scalp, neck, trunk, and axillae, and “other cutaneous manifestations have been reported in patients,” Dr. Callen said.

The disease also frequently affects the bones, large vessels, heart, lungs, and central nervous system. Interferon-alpha is the first-line treatment, and there are several other alternative therapies, although 5-year survival (68%) is poor, and it is especially likely to be fatal in those with central nervous system involvement.
 

Eosinophilic fasciitis

Eosinophilic fasciitis (EF) “is a disorder of unknown etiology that causes sclerosis of the skin” without Raynaud’s phenomenon, Dr. Callen said. Look for erythema, swelling, and induration of the extremities that is accompanied by peripheral eosinophilia, and if necessary, confirm the diagnosis with full skin-to-muscle biopsy or MRI.

There are many possible triggers, including strenuous exercise, initiation with hemodialysis, radiation therapy and burns, and graft-versus-host disease. Other potential causes include exposure to medications such as statins, phenytoin, ramipril, subcutaneous heparin, and immune checkpoint inhibitor therapy. The disorder is also linked to autoimmune and hematologic disorders.

Dr. Callen, who highlighted EF guidelines published in 2018, said treatments include physical therapy, prednisone, methotrexate, mycophenolate, and hydroxychloroquine.
 

Metastatic Crohn’s disease

This is a rare granulomatous inflammation of skin that often affects the genitals, especially in children. It is noncontiguous with the GI tract, and severity of skin involvement does not always parallel the severity of the disease in the GI tract, Dr. Callen said. However, the condition can occur before or simultaneously with the development of GI disease, or after GI surgery.

He highlighted a review of metastatic Crohn’s disease, published in 2014, and noted that there are multiple treatments, including systemic corticosteroids, tumor necrosis factor–alpha inhibitors, and topical therapies.

Dr. Callen reported no relevant disclosures.

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at [email protected].

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at [email protected].

Two chronic gynecologic conditions notably affect a woman’s quality of life (QoL), including fertility – one is endometriosis, and the other is a fibroid uterus. For a benign tumor, fibroids have an impressive prevalence found in approximately 50%-60% of women during their reproductive years. By menopause, it is estimated that 70% of woman have a fibroid, yet the true incidence is unknown given that only 25% of women experience symptoms bothersome enough to warrant intervention. This month’s article reviews the burden of fibroids and the latest management options that may potentially avoid surgery.

Background

Fibroids are monoclonal tumors of uterine smooth muscle that originate from the myometrium. Risk factors include family history, being premenopausal, increasing time since last delivery, obesity, and hypertension (ACOG Practice Bulletin no. 228 Jun 2021: Obstet Gynecol. 2021 Jun 1;137[6]:e100-e15) but oral hormonal contraception, depot medroxyprogesterone acetate (MPA), and increased parity reduce the risk of fibroids. Compared with White women, Black women have a 2-3 times higher prevalence of fibroids, develop them at a younger age, and present with larger fibroids.

The FIGO leiomyoma classification is the agreed upon system for identifying fibroid location. Symptoms are all too familiar to gynecologists, with life-threatening hemorrhage with severe anemia being the most feared, particularly for FIGO types 1-5. Transvaginal ultrasound is the simplest imaging tool for evaluation.

Adapted from Int J Gynecol Obstet. 2011;113:3-13.

Fibroids and fertility

Fibroids can impair fertility in several ways: alteration of local anatomy, including the detrimental effects of abnormal uterine bleeding; functional changes by increasing uterine contractions and impairing endometrium and myometrial blood supply; and changes to the local hormonal environment that could impair egg/sperm transport, or embryo implantation (Hum Reprod Update. 2017;22:665-86).

Prior to consideration of surgery, saline infusion sonogram can determine the degree of impact on the endometrium, which is most applicable to the infertility patient, but can also allow guidance toward the appropriate surgical approach.
 

Treatment options – medical

Management of fibroids is based on a woman’s age, desire for fertility, symptoms, and location of the fibroid(s). Expectant observation of a woman with fibroids may be a reasonable approach, provided the lack of symptoms impairing QoL and of anemia. Typically, there is no change in fibroid size during the short term, considered less than 1 year. Regarding fertility, studies are heterogeneous so there is no definitive conclusion that fibroids impair natural fertility (Reprod Biomed Online. 2021;43:100-10). Spontaneous regression, defined by a reduction in fibroid volume of greater than 20%, has been noted to occur in 7.0% of fibroids (Curr Obstet Gynecol Rep. 2018;7[3]:117-21).

When fertility is not desired, medical management of fibroids is the initial conservative approach. GnRH agonists have been utilized for temporary relief of menometrorrhagia because of fibroids and to reduce their volume, particularly preoperatively. However, extended treatment can induce bone mineral density loss. Add-back therapy (tibolone, raloxifene, estriol, and ipriflavone) is of value in reducing bone loss while MPA and tibolone may manage vasomotor symptoms. More recently, the use of a GnRH antagonist (elagolix) along with add-back therapy has been approved for up to 24 months by the Food and Drug Administration and has demonstrated a more than 50% amenorrhea rate at 12 months (Obstet Gynecol. 2020;135:1313-26).

Progesterone plays an important role in fibroid growth, but the mechanism is unclear. Although not FDA approved, selective progesterone receptor modulators (SPRM) act directly on fibroid size reduction at the level of the pituitary to induce amenorrhea through inhibition of ovulation. Also, more than one course of SPRMs can provide benefit for bleeding control and volume reduction. The SPRM ulipristal acetate for four courses of 3 months demonstrated 73.5% of patients experienced a fibroid volume reduction of greater than 25% and were amenorrheic (Fertil Steril. 2017;108:416-25). GnRH agonists or SPRMs may benefit women if the fibroid is larger than 3 cm or anemia exists, thereby precluding immediate surgery.

Other medication options include the levonorgestrel IUD, combined hormonal contraceptives, and tranexamic acid – all of which have limited data on effective results of treating abnormal uterine bleeding.
 

Treatment options – surgical

Fibroids are the most common reason for hysterectomy as they are the contributing indication in approximately one-third of surgeries. When future fertility is desired, current surgical options include hysteroscopic and laparoscopic (including robotic) myomectomy. Hysteroscopy is the standard approach for FIGO type 1 fibroids and can also manage some type 2 fibroids provided they are less than 3 cm and the latter is greater than 5 mm from the serosa. Type 2 fibroids may benefit from a “two-step” removal to allow the myometrium to contract and extrude the fibroid. In light of the risk of fluid overload with nonelectrolyte solutions that enable the use of monopolar cautery, many procedures are now performed with bipolar cautery or morcellators.

Laparoscopy (including robotic) has outcomes similar to those of laparotomy although the risk of uterine rupture with the former requires careful attention to thorough closure of the myometrial defect. Robotic myomectomy has outcomes similar to those of standard laparoscopy with less blood loss, but operating times may be prolonged (Best Pract Res Clin Obstet Gynaecol. 2018;46:113-9).

The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women (Fertil Steril 2017;108;416-25). The rate of recurrence after myomectomy can be as great as 60% when patients are followed up to 5 years. Intramural fibroids greater than 2.85 cm and not distorting the uterine cavity may decrease in vitro fertilization (IVF) success (Fertil Steril 2014;101:716-21).
 

Noninvasive treatment modalities

Uterine artery embolization (UAE) is the most popular minimally invasive alternative to surgical myomectomy. Risks include postembolization syndrome (pain, fever, nausea, leukocytosis, and occasionally malaise), infection, and damage to fertility. Rarely, loss of ovarian function can occur, particularly in women above age 45. Because of the disruption of uterine blood flow, UAE increases the risk of accelerating ovarian aging and infertility as well as atrophic endometrium. In addition, pregnancy complications are increased including miscarriage, preterm labor, and postpartum hemorrhage. There is debate regarding the need for cesarean section at time of delivery given the potential for weakening of the uterine wall following UAE.

High-intensity focused ultrasound (HIFU) is guided by ultrasound or MRI and involves a high-energy-density ultrasound wave passing through the skin. The wave is absorbed and transformed into heat, causing the tissue protein to coagulate, and to be absorbed by the body. The procedure is scarless, carries a minimal risk of infection, and offers less pain compared with traditional approaches. However, HIFU is time consuming, and skin burns and unintentional tissue injury are a risk. A meta-analysis demonstrated improved symptoms of fibroids at 6 and 12 months (J Min Invasive Gynecol. 2021 in press).

Ultrasound-guided microwave ablation (MWA) uses an ablative electrode that is directly inserted into the target tissue via transcutaneous or transcervical approach via ultrasound guidance using microwave to produce heat for tissue coagulation necrosis. The advantages of MWA compared with HIFU and RFA are a higher tissue temperature, larger ablation volume, shorter operating time, less pain and no adverse major events (J Min Invasive Gynecol. 2021, in press).
 

Conclusion

The current literature cannot conclude that fibroids reduce the likelihood of achieving pregnancy with or without fertility treatment, based on a specific size, number, or location (not including submucosal or cavity-distorting intramural fibroids). Definitive evidence on the efficacy of myomectomy to improve fertility remains limited. Hysteroscopic myomectomy presumably improves pregnancy rates, but there is uncertainty as to its role in reducing miscarriage. Novel nonsurgical modalities are available and are expected to continue being developed but clarity on fertility outcomes is needed.
 

Dr. Trolice is director of Fertility CARE – The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. He has no conflicts of interests. Please contact him at [email protected].

An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.

In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.

Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.

The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.

“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
 

‘Surprising’ improvement seen

The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.

All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.

One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.

While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.

“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”

While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
 

Implication for other disorders

Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.

“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”

The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.


 

An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.

In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.

Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.

The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.

“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
 

‘Surprising’ improvement seen

The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.

All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.

One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.

While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.

“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”

While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
 

Implication for other disorders

Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.

“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”

The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.


 

An experimental gene therapy produced marked clinical improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder that affects the synthesis of key neurotransmitters to cause severe developmental and motor disability.

In an article published July 12, 2021, in Nature Communications, a group of researchers based at the University of California, San Francisco, and Ohio State University, Columbus, described results from seven children ages 4-9 with AADC deficiency who underwent a novel form of surgery to deliver a viral vector expressing the human AADC gene to the midbrain.

Previous trials of this gene therapy in children with AADC deficiency targeted a different region of the brain, the putamen, with only slight clinical improvement. Here, investigators chose two midbrain regions – the substantia nigra pars compacta and the ventral tegmental area – in the hope of restoring healthy AADC enzyme activity in those neurons.

The study’s corresponding author, Krystof Bankiewicz, MD, PhD, professor and vice chair of research at Ohio State University, director of the Brain Health and Performance Center at Ohio State University, and professor emeritus and vice chair for research at UCSF, said in an interview that the brain regions chosen for this trial resulted from years of efforts to identify an ideal target in this disease.

“This particular vector undergoes axonal transport,” he said. “If you inject it into specific regions of the brain it will be transported into the terminals [of the nerve fibers]. And by looking at the imaging of these patients, we found that they still have the wiring in the brain that’s so critical. So we decided to aim at a much more difficult target, going directly to the source of the problem, which is the substantia nigra and the ventral tegmental area. This targets two critical pathways in the brain: one that drives motor responses and another that controls emotions.”
 

‘Surprising’ improvement seen

The children in the study – four girls and three boys – underwent surgery from 2016 to the end of 2018, and were divided into two dose cohorts, with one receiving three times the amount of vector as the other. Both groups, however, saw similar levels of improvement.

All but one child saw complete resolution of a hallmark symptom of the disease – oculogyric crises, or prolonged spasms of muscles controlling eye movement – within 3 months of surgery. Of the children followed at least 18 months, six attained head control within a year, two became able to eat and drink by mouth, and four gained the ability to sit up unaided in that time. At 18 months one child had learned to speak 50 words using an augmentative communication device.

One child died unexpectedly 7 months after the procedure, Dr. Bankiewicz said in an interview. This death appeared to be caused by cardiac complications of his disease, Dr. Bankiewicz said, which are common in AADC deficiency.

While the investigators are now looking at delivering the AADC gene therapy in younger children – who were excluded from this trial because of safety concerns surrounding the complex procedure – investigators were surprised by the level of improvement seen in older children.

“We initially didn’t believe – at least not all of us – that we could actually make an impact in the older patients, and that is not the case,” said Dr. Bankiewicz, who has since used the same gene therapy on a compassionate-use basis in Europe and seen durable clinical improvement in patients as old as 26. “The fact that we saw a response in that patient tells us something about how incredibly plastic the brain is.”

While the new study does not detail improvements in the children’s social and emotional well-being, Dr. Bankiewicz said these, too, were pronounced. “Kids fall into oculogyric crises in stress-inducing situation. They might be in a stroller being taken for a walk, and something in the environment would stress them. Sometimes they had to be kept in a dark room isolated from stress.” Following the gene therapy, “they’re laughing, they’re social, they can interact with their environment. It’s really touching to see them able to develop a bond now with their caregivers.”
 

Implication for other disorders

Dr. Bankiewicz and colleagues have previously used the same gene to boost AADC activity in patients with Parkinson’s disease. The group is also in trials to deliver a neuroprotective gene to the brains of people with early-stage Alzheimer’s disease, and a gene-silencing therapy in patients with Huntington’s disease. They will also continue recruiting pediatric patients for trials of the AADC gene therapy.

“We have been developing a method for safely treating younger children, so now we will go to 3 years old and maybe even below,” Dr. Bankiewicz said. “Earlier is probably better, but for technical and safety considerations we needed to be conservative first. It is hugely stressful to go into very sick patients with that type of therapy in that part of the brain. We had to get it right the first time, and it looks like we did.”

The study was funded by the National Institutes of Health, the AADC Research Trust, the Pediatric Neurotransmitter Disease Association, and Ohio State University, with materials and technical support donated by ClearPoint Neuro. Several coauthors disclosed financial relationships with producers of diagnostic tests or biotechnology firms. Dr. Bankiewicz is a founder and shareholder of Brain Neurotherapy Bio, a company that develops gene therapies for Parkinson’s and other diseases.


 

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

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

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

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

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).

PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.

In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.

Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.

There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.

“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.

“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.

The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.

PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).

In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.

Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.

Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.

Full prescribing information is available online.

“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.

The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.

Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.

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

The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).

PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.

In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.

Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.

There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.

“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.

“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.

The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.

PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).

In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.

Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.

Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.

Full prescribing information is available online.

“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.

The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.

Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.

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

The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).

PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.

In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.

Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.

There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.

“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.

“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.

The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.

PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).

In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.

Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.

Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.

Full prescribing information is available online.

“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.

The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.

Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.

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