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Trial of Impella Heart Pump Stopped
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.
Mounjaro Beats Ozempic, So Why Isn’t It More Popular?
This transcript has been edited for clarity.
It’s July, which means our hospital is filled with new interns, residents, and fellows all eager to embark on a new stage of their career. It’s an exciting time — a bit of a scary time — but it’s also the time when the medical strategies I’ve been taking for granted get called into question. At this point in the year, I tend to get a lot of “why” questions. Why did you order that test? Why did you suspect that diagnosis? Why did you choose that medication?
Meds are the hardest, I find. Sure, I can explain that I prescribed a glucagon-like peptide 1 (GLP-1) receptor agonist because the patient had diabetes and was overweight, and multiple studies show that this class of drug leads to weight loss and reduced mortality risk. But then I get the follow-up: Sure, but why THAT GLP-1 drug? Why did you pick semaglutide (Ozempic) over tirzepatide (Mounjaro)?
Here’s where I run out of good answers. Sometimes I choose a drug because that’s what the patient’s insurance has on their formulary. Sometimes it’s because it’s cheaper in general. Sometimes, it’s just force of habit. I know the correct dose, I have experience with the side effects — it’s comfortable.
What I can’t say is that I have solid evidence that one drug is superior to another, say from a randomized trial of semaglutide vs tirzepatide. I don’t have that evidence because that trial has never happened and, as I’ll explain in a minute, may never happen at all.
But we might have the next best thing. And the results may surprise you.
Why don’t we see more head-to-head trials of competitor drugs? The answer is pretty simple, honestly: risk management. For drugs that are on patent, like the GLP-1s, conducting a trial without the buy-in of the pharmaceutical company is simply too expensive — we can’t run a trial unless someone provides the drug for free. That gives the companies a lot of say in what trials get done, and it seems that most pharma companies have reached the same conclusion: A head-to-head trial is too risky. Be happy with the market share you have, and try to nibble away at the edges through good old-fashioned marketing.
But if you look at the data that are out there, you might wonder why Ozempic is the market leader. I mean, sure, it’s a heck of a weight loss drug. But the weight loss in the trials of Mounjaro was actually a bit higher. It’s worth noting here that tirzepatide (Mounjaro) is not just a GLP-1 receptor agonist; it is also a gastric inhibitory polypeptide agonist. 
But it’s very hard to compare the results of a trial pitting Ozempic against placebo with a totally different trial pitting Mounjaro against placebo. You can always argue that the patients studied were just too different at baseline — an apples and oranges situation.
Newly published, a study appearing in JAMA Internal Medicine uses real-world data and propensity-score matching to turn oranges back into apples. I’ll walk you through it.
The data and analysis here come from Truveta, a collective of various US healthcare systems that share a broad swath of electronic health record data. Researchers identified 41,222 adults with overweight or obesity who were prescribed semaglutide or tirzepatide between May 2022 and September 2023.
You’d be tempted to just see which group lost more weight over time, but that is the apples and oranges problem. People prescribed Mounjaro were different from people who were prescribed Ozempic. There are a variety of factors to look at here, but the vibe is that the Mounjaro group seems healthier at baseline. They were younger and had less kidney disease, less hypertension, and less hyperlipidemia. They had higher incomes and were more likely to be White. They were also dramatically less likely to have diabetes. 
To account for this, the researchers used a statistical technique called propensity-score matching. Briefly, you create a model based on a variety of patient factors to predict who would be prescribed Ozempic and who would be prescribed Mounjaro. You then identify pairs of patients with similar probability (or propensity) of receiving, say, Ozempic, where one member of the pair got Ozempic and one got Mounjaro. Any unmatched individuals simply get dropped from the analysis.
Thus, the researchers took the 41,222 individuals who started the analysis, of whom 9193 received Mounjaro, and identified the 9193 patients who got Ozempic that most closely matched the Mounjaro crowd. I know, it sounds confusing. But as an example, in the original dataset, 51.9% of those who got Mounjaro had diabetes compared with 71.5% of those who got Ozempic. Among the 9193 individuals who remained in the Ozempic group after matching, 52.1% had diabetes. By matching in this way, you balance your baseline characteristics. Turning apples into oranges. Or, maybe the better metaphor would be plucking the oranges out of a big pile of mostly apples.
Once that’s done, we can go back to do what we wanted to do in the beginning, which is to look at the weight loss between the groups.
What I’m showing you here is the average percent change in body weight at 3, 6, and 12 months across the two drugs in the matched cohort. By a year out, you have basically 15% weight loss in the Mounjaro group compared with 8% or so in the Ozempic group. 
We can slice this a different way as well — asking what percent of people in each group achieve, say, 10% weight loss? This graph examines the percentage of each treatment group who hit that weight loss target over time. Mounjaro gets there faster.
I should point out that this was a so-called “on treatment” analysis: If people stopped taking either of the drugs, they were no longer included in the study. That tends to make drugs like this appear better than they are because as time goes on, you may weed out the people who stop the drug owing to lack of efficacy or to side effects. But in a sensitivity analysis, the authors see what happens if they just treat people as if they were taking the drug for the entire year once they had it prescribed, and the results, while not as dramatic, were broadly similar. Mounjaro still came out on top.
Adverse events— stuff like gastroparesis and pancreatitis — were rare, but rates were similar between the two groups.
It’s great to see studies like this that leverage real world data and a solid statistical underpinning to give us providers actionable information. Is it 100% definitive? No. But, especially considering the clinical trial data, I don’t think I’m going out on a limb to say that Mounjaro seems to be the more effective weight loss agent. That said, we don’t actually live in a world where we can prescribe medications based on a silly little thing like which is the most effective. Especially given the cost of these agents — the patient’s insurance status is going to guide our prescription pen more than this study ever could. And of course, given the demand for this class of agents and the fact that both are actually quite effective, you may be best off prescribing whatever you can get your hands on.
But I’d like to see more of this. When I do have a choice of a medication, when costs and availability are similar, I’d like to be able to answer that question of “why did you choose that one?” with an evidence-based answer: “It’s better.”
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
It’s July, which means our hospital is filled with new interns, residents, and fellows all eager to embark on a new stage of their career. It’s an exciting time — a bit of a scary time — but it’s also the time when the medical strategies I’ve been taking for granted get called into question. At this point in the year, I tend to get a lot of “why” questions. Why did you order that test? Why did you suspect that diagnosis? Why did you choose that medication?
Meds are the hardest, I find. Sure, I can explain that I prescribed a glucagon-like peptide 1 (GLP-1) receptor agonist because the patient had diabetes and was overweight, and multiple studies show that this class of drug leads to weight loss and reduced mortality risk. But then I get the follow-up: Sure, but why THAT GLP-1 drug? Why did you pick semaglutide (Ozempic) over tirzepatide (Mounjaro)?
Here’s where I run out of good answers. Sometimes I choose a drug because that’s what the patient’s insurance has on their formulary. Sometimes it’s because it’s cheaper in general. Sometimes, it’s just force of habit. I know the correct dose, I have experience with the side effects — it’s comfortable.
What I can’t say is that I have solid evidence that one drug is superior to another, say from a randomized trial of semaglutide vs tirzepatide. I don’t have that evidence because that trial has never happened and, as I’ll explain in a minute, may never happen at all.
But we might have the next best thing. And the results may surprise you.
Why don’t we see more head-to-head trials of competitor drugs? The answer is pretty simple, honestly: risk management. For drugs that are on patent, like the GLP-1s, conducting a trial without the buy-in of the pharmaceutical company is simply too expensive — we can’t run a trial unless someone provides the drug for free. That gives the companies a lot of say in what trials get done, and it seems that most pharma companies have reached the same conclusion: A head-to-head trial is too risky. Be happy with the market share you have, and try to nibble away at the edges through good old-fashioned marketing.
But if you look at the data that are out there, you might wonder why Ozempic is the market leader. I mean, sure, it’s a heck of a weight loss drug. But the weight loss in the trials of Mounjaro was actually a bit higher. It’s worth noting here that tirzepatide (Mounjaro) is not just a GLP-1 receptor agonist; it is also a gastric inhibitory polypeptide agonist.
But it’s very hard to compare the results of a trial pitting Ozempic against placebo with a totally different trial pitting Mounjaro against placebo. You can always argue that the patients studied were just too different at baseline — an apples and oranges situation.
Newly published, a study appearing in JAMA Internal Medicine uses real-world data and propensity-score matching to turn oranges back into apples. I’ll walk you through it.
The data and analysis here come from Truveta, a collective of various US healthcare systems that share a broad swath of electronic health record data. Researchers identified 41,222 adults with overweight or obesity who were prescribed semaglutide or tirzepatide between May 2022 and September 2023.
You’d be tempted to just see which group lost more weight over time, but that is the apples and oranges problem. People prescribed Mounjaro were different from people who were prescribed Ozempic. There are a variety of factors to look at here, but the vibe is that the Mounjaro group seems healthier at baseline. They were younger and had less kidney disease, less hypertension, and less hyperlipidemia. They had higher incomes and were more likely to be White. They were also dramatically less likely to have diabetes.
To account for this, the researchers used a statistical technique called propensity-score matching. Briefly, you create a model based on a variety of patient factors to predict who would be prescribed Ozempic and who would be prescribed Mounjaro. You then identify pairs of patients with similar probability (or propensity) of receiving, say, Ozempic, where one member of the pair got Ozempic and one got Mounjaro. Any unmatched individuals simply get dropped from the analysis.
Thus, the researchers took the 41,222 individuals who started the analysis, of whom 9193 received Mounjaro, and identified the 9193 patients who got Ozempic that most closely matched the Mounjaro crowd. I know, it sounds confusing. But as an example, in the original dataset, 51.9% of those who got Mounjaro had diabetes compared with 71.5% of those who got Ozempic. Among the 9193 individuals who remained in the Ozempic group after matching, 52.1% had diabetes. By matching in this way, you balance your baseline characteristics. Turning apples into oranges. Or, maybe the better metaphor would be plucking the oranges out of a big pile of mostly apples.
Once that’s done, we can go back to do what we wanted to do in the beginning, which is to look at the weight loss between the groups.
What I’m showing you here is the average percent change in body weight at 3, 6, and 12 months across the two drugs in the matched cohort. By a year out, you have basically 15% weight loss in the Mounjaro group compared with 8% or so in the Ozempic group.
We can slice this a different way as well — asking what percent of people in each group achieve, say, 10% weight loss? This graph examines the percentage of each treatment group who hit that weight loss target over time. Mounjaro gets there faster.
I should point out that this was a so-called “on treatment” analysis: If people stopped taking either of the drugs, they were no longer included in the study. That tends to make drugs like this appear better than they are because as time goes on, you may weed out the people who stop the drug owing to lack of efficacy or to side effects. But in a sensitivity analysis, the authors see what happens if they just treat people as if they were taking the drug for the entire year once they had it prescribed, and the results, while not as dramatic, were broadly similar. Mounjaro still came out on top.
Adverse events— stuff like gastroparesis and pancreatitis — were rare, but rates were similar between the two groups.
It’s great to see studies like this that leverage real world data and a solid statistical underpinning to give us providers actionable information. Is it 100% definitive? No. But, especially considering the clinical trial data, I don’t think I’m going out on a limb to say that Mounjaro seems to be the more effective weight loss agent. That said, we don’t actually live in a world where we can prescribe medications based on a silly little thing like which is the most effective. Especially given the cost of these agents — the patient’s insurance status is going to guide our prescription pen more than this study ever could. And of course, given the demand for this class of agents and the fact that both are actually quite effective, you may be best off prescribing whatever you can get your hands on.
But I’d like to see more of this. When I do have a choice of a medication, when costs and availability are similar, I’d like to be able to answer that question of “why did you choose that one?” with an evidence-based answer: “It’s better.”
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
It’s July, which means our hospital is filled with new interns, residents, and fellows all eager to embark on a new stage of their career. It’s an exciting time — a bit of a scary time — but it’s also the time when the medical strategies I’ve been taking for granted get called into question. At this point in the year, I tend to get a lot of “why” questions. Why did you order that test? Why did you suspect that diagnosis? Why did you choose that medication?
Meds are the hardest, I find. Sure, I can explain that I prescribed a glucagon-like peptide 1 (GLP-1) receptor agonist because the patient had diabetes and was overweight, and multiple studies show that this class of drug leads to weight loss and reduced mortality risk. But then I get the follow-up: Sure, but why THAT GLP-1 drug? Why did you pick semaglutide (Ozempic) over tirzepatide (Mounjaro)?
Here’s where I run out of good answers. Sometimes I choose a drug because that’s what the patient’s insurance has on their formulary. Sometimes it’s because it’s cheaper in general. Sometimes, it’s just force of habit. I know the correct dose, I have experience with the side effects — it’s comfortable.
What I can’t say is that I have solid evidence that one drug is superior to another, say from a randomized trial of semaglutide vs tirzepatide. I don’t have that evidence because that trial has never happened and, as I’ll explain in a minute, may never happen at all.
But we might have the next best thing. And the results may surprise you.
Why don’t we see more head-to-head trials of competitor drugs? The answer is pretty simple, honestly: risk management. For drugs that are on patent, like the GLP-1s, conducting a trial without the buy-in of the pharmaceutical company is simply too expensive — we can’t run a trial unless someone provides the drug for free. That gives the companies a lot of say in what trials get done, and it seems that most pharma companies have reached the same conclusion: A head-to-head trial is too risky. Be happy with the market share you have, and try to nibble away at the edges through good old-fashioned marketing.
But if you look at the data that are out there, you might wonder why Ozempic is the market leader. I mean, sure, it’s a heck of a weight loss drug. But the weight loss in the trials of Mounjaro was actually a bit higher. It’s worth noting here that tirzepatide (Mounjaro) is not just a GLP-1 receptor agonist; it is also a gastric inhibitory polypeptide agonist.
But it’s very hard to compare the results of a trial pitting Ozempic against placebo with a totally different trial pitting Mounjaro against placebo. You can always argue that the patients studied were just too different at baseline — an apples and oranges situation.
Newly published, a study appearing in JAMA Internal Medicine uses real-world data and propensity-score matching to turn oranges back into apples. I’ll walk you through it.
The data and analysis here come from Truveta, a collective of various US healthcare systems that share a broad swath of electronic health record data. Researchers identified 41,222 adults with overweight or obesity who were prescribed semaglutide or tirzepatide between May 2022 and September 2023.
You’d be tempted to just see which group lost more weight over time, but that is the apples and oranges problem. People prescribed Mounjaro were different from people who were prescribed Ozempic. There are a variety of factors to look at here, but the vibe is that the Mounjaro group seems healthier at baseline. They were younger and had less kidney disease, less hypertension, and less hyperlipidemia. They had higher incomes and were more likely to be White. They were also dramatically less likely to have diabetes.
To account for this, the researchers used a statistical technique called propensity-score matching. Briefly, you create a model based on a variety of patient factors to predict who would be prescribed Ozempic and who would be prescribed Mounjaro. You then identify pairs of patients with similar probability (or propensity) of receiving, say, Ozempic, where one member of the pair got Ozempic and one got Mounjaro. Any unmatched individuals simply get dropped from the analysis.
Thus, the researchers took the 41,222 individuals who started the analysis, of whom 9193 received Mounjaro, and identified the 9193 patients who got Ozempic that most closely matched the Mounjaro crowd. I know, it sounds confusing. But as an example, in the original dataset, 51.9% of those who got Mounjaro had diabetes compared with 71.5% of those who got Ozempic. Among the 9193 individuals who remained in the Ozempic group after matching, 52.1% had diabetes. By matching in this way, you balance your baseline characteristics. Turning apples into oranges. Or, maybe the better metaphor would be plucking the oranges out of a big pile of mostly apples.
Once that’s done, we can go back to do what we wanted to do in the beginning, which is to look at the weight loss between the groups.
What I’m showing you here is the average percent change in body weight at 3, 6, and 12 months across the two drugs in the matched cohort. By a year out, you have basically 15% weight loss in the Mounjaro group compared with 8% or so in the Ozempic group.
We can slice this a different way as well — asking what percent of people in each group achieve, say, 10% weight loss? This graph examines the percentage of each treatment group who hit that weight loss target over time. Mounjaro gets there faster.
I should point out that this was a so-called “on treatment” analysis: If people stopped taking either of the drugs, they were no longer included in the study. That tends to make drugs like this appear better than they are because as time goes on, you may weed out the people who stop the drug owing to lack of efficacy or to side effects. But in a sensitivity analysis, the authors see what happens if they just treat people as if they were taking the drug for the entire year once they had it prescribed, and the results, while not as dramatic, were broadly similar. Mounjaro still came out on top.
Adverse events— stuff like gastroparesis and pancreatitis — were rare, but rates were similar between the two groups.
It’s great to see studies like this that leverage real world data and a solid statistical underpinning to give us providers actionable information. Is it 100% definitive? No. But, especially considering the clinical trial data, I don’t think I’m going out on a limb to say that Mounjaro seems to be the more effective weight loss agent. That said, we don’t actually live in a world where we can prescribe medications based on a silly little thing like which is the most effective. Especially given the cost of these agents — the patient’s insurance status is going to guide our prescription pen more than this study ever could. And of course, given the demand for this class of agents and the fact that both are actually quite effective, you may be best off prescribing whatever you can get your hands on.
But I’d like to see more of this. When I do have a choice of a medication, when costs and availability are similar, I’d like to be able to answer that question of “why did you choose that one?” with an evidence-based answer: “It’s better.”
Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Chronic Neck Pain: A Primary Care Approach
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain?
Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second.
The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.
The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.
We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.
You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage.
Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other.
The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery.
What about cervical myelopathy, Paul? Do those patients need surgery?
Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it.
Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery.
We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.
Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain?
Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second.
The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.
The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.
We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.
You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage.
Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other.
The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery.
What about cervical myelopathy, Paul? Do those patients need surgery?
Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it.
Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery.
We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.
Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Matthew F. Watto, MD: Welcome to The Curbsiders. I’m here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. We’re going to be talking about the evaluation of chronic neck pain, which is a really common complaint in primary care. So, Paul, what are the three buckets of neck pain?
Paul N. Williams, MD: Well, as our listeners probably know, neck pain is extraordinarily common. There are three big buckets. There is mechanical neck pain, which is sort of the bread-and-butter “my neck just hurts” — probably the one you’re going to see most commonly in the office. We’ll get into that in just a second.
The second bucket is cervical radiculopathy. We see a little bit more neurologic symptoms as part of the presentation. They may have weakness. They may have pain.
The third type of neck pain is cervical myelopathy, which is the one that probably warrants more aggressive follow-up and evaluation, and potentially even management. And that is typically your older patients in nontraumatic cases, who have bony impingement on the central spinal cord, often with upper motor neuron signs, and it can ultimately be very devastating. It’s almost a spectrum of presentations to worry about in terms of severity and outcomes.
We’ll start with the mechanical neck pain. It’s the one that we see the most commonly in the primary care office. We’ve all dealt with this. This is the patient who’s got localized neck pain that doesn’t really radiate anywhere; it kind of sits in the middle of the neck. In fact, if you actually poke back there where the patient says “ouch,” you’re probably in the right ballpark. The etiology and pathophysiology, weirdly, are still not super well-defined, but it’s probably mostly myofascial in etiology. And as such, it often gets better no matter what you do. It will probably get better with time.
You are not going to have neurologic deficits with this type of neck pain. There’s not going to be weakness, or radiation down the arm, or upper motor neuron signs. No one is mentioning the urinary symptoms with this. You can treat it with NSAIDs and physical therapy, which may be necessary if it persists. Massage can sometimes be helpful, but basically you’re just kind of supporting the patients through their own natural healing process. Physical therapy might help with the ergonomics and help make sure that they position themselves and move in a way that does not exacerbate the underlying structures. That is probably the one that we see the most and in some ways is probably the easiest to manage.
Dr. Watto: This is the one that we generally should be least worried about. But cervical radiculopathy, which is the second bucket, is not as severe as cervical myelopathy, so it’s kind of in between the two. Cervical radiculopathy is basically the patient who has neck pain that’s going down one arm or the other, usually not both arms because that would be weird for them to have symmetric radiculopathy. It’s a nerve being pinched somewhere, usually more on one side than the other.
The good news for patients is that the natural history is that it’s going to get better over time, almost no matter what we do. I almost think of this akin to sciatica. Usually sciatica and cervical radiculopathy do not have any motor weakness along with them. It’s really just the pain and maybe a little bit of mild sensory symptoms. So, you can reassure the patient that this usually goes away. Our guest said he sometimes gives gabapentin for this. That’s not my practice. I would be more likely to refer to physical therapy or try some NSAIDs if they’re really having trouble functioning or maybe some muscle relaxants. But they aren’t going to need to go to surgery.
What about cervical myelopathy, Paul? Do those patients need surgery?
Dr. Williams: Yes. The idea with cervical myelopathy is to keep it from progressing. It typically occurs in older patients. It’s like arthritis — a sort of bony buildup that compresses on the spinal cord itself. These patients will often have neck pain but not always. It’s also associated with impairments in motor function and other neurologic deficits. So, the patients may report that they have difficulty buttoning their buttons or managing fine-motor skills. They may have radicular symptoms down their arms. They may have an abnormal physical examination. They may have weakness on exam, but they’ll have a positive Hoffmann’s test where you flick the middle finger and look for flexion of the first finger and the thumb. They may have abnormal tandem gait, or patellar or Achilles hyperreflexia. Their neuro exam will not be normal much of the time, and in later cases because it’s upper motor neuron disease, they may even report urinary symptoms like urinary hesitancy or just a feeling of general unsteadiness of the gait, even though we’re at the cervical level. If you suspect myelopathy — and the trick is to think about it and recognize it when you see it — then you should send them for an MRI. If it persists or they have rapid regression, you get the MRI and refer them to neurosurgery. It’s not necessarily a neurosurgical emergency, but things should move along fairly briskly once you’ve actually identified it.
Dr. Watto: Dr. Mikula made the point that if someone comes to you in a wheelchair, they are probably not going to regain the ability to walk. You’re really trying to prevent progression. If they are already severely disabled, they’re probably not going to get totally back to full functioning, even with surgery. You’re just trying to prevent things from getting worse. That’s the main reason to identify this and get the patient to surgery.
We covered a lot more about neck pain. This was a very superficial review of what we talked about with Dr. Anthony Mikula. Click here to listen to the full podcast.
Matthew F. Watto is clinical assistant professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania, and internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania. He has disclosed no relevant financial relationships. Paul N. Williams is associate professor of clinical medicine, Department of General Internal Medicine, Lewis Katz School of Medicine, and staff physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania. He has disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for The Curbsiders; received income in an amount equal to or greater than $250 from The Curbsiders.
A version of this article first appeared on Medscape.com.
Does Medicare Enrollment Raise Diabetes Medication Costs?
TOPLINE:
Reaching age 65 years and enrolling in Medicare is associated with a $23 increase in quarterly out-of-pocket costs for type 2 diabetes (T2D) medications. Medication usage decreased by 5.3%, with a notable shift toward more expensive insulin use.
METHODOLOGY:
- Researchers conducted a retrospective cohort study using 2012-2020 prescription drug claims data from the TriNetX Diamond Network.
- A total of 129,997 individuals diagnosed with T2D were included, with claims observed both before and after age 65 years.
- The primary outcome was patient out-of-pocket costs for T2D drugs per quarter, adjusted to 2020 dollars.
- Drugs measured included biguanides (metformin), sulfonylureas, thiazolidinediones, insulin, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2 inhibitors), and amylin analogs, among others.
- Regression discontinuity design was used to examine the outcomes, adjusting for differential linear quarterly time trends, year fixed effects, and utilization composition and intensity.
TAKEAWAY:
- Reaching age 65 years was associated with an increase of $23.04 in mean quarterly out-of-pocket costs for T2D drugs (95% confidence interval [CI], $19.86-$26.22).
- The 95th percentile of out-of-pocket spending increased by $56.36 (95% CI, $51.48-$61.23) after utilization adjustment.
- T2D medication usage decreased by 5.3% at age 65 years, from 3.40 claims per quarter to 3.22 claims per quarter.
- Higher out-of-pockets were associated with insulin use, DPP-4 inhibitors, GLP-1s, and SGLT2 inhibitors.
IN PRACTICE:
“Our results have important implications for the provisions of the Inflation Reduction Act, many of which aim to reduce these costs. Reduced patient cost burden will improve adherence and the management of type 2 diabetes, likely leading to reductions in T2D complications,” wrote the authors of the study.
SOURCE:
The study was led by Douglas Barthold, PhD, Jing Li, MA, PhD, and Anirban Basu, MS, PhD, at the Comparative Health Outcomes, Policy, and Economics Institute, School of Pharmacy, University of Washington, Seattle. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s limitations include the possibility that not all claims of an individual were observed, as TriNetX claims data may not capture individuals who leave the healthcare system or have inaccurate or changing diagnoses. Additionally, the data lack individual-level insurance characteristics. The assumption that individuals transition to Medicare at age 65 years may not be true for all participants. The study also lacks clinical information regarding the severity of T2D, which could influence medication usage and out-of-pocket costs.
DISCLOSURES:
The study was supported by grants from the National Institute on Aging (NIA) and the University of Washington’s Population Health Initiative, Student Technology Fee program, and Provost’s office. Dr. Barthold and Dr. Li received grants from the NIA. Dr. Basu reported receiving personal fees from Salutis Consulting LLC outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Reaching age 65 years and enrolling in Medicare is associated with a $23 increase in quarterly out-of-pocket costs for type 2 diabetes (T2D) medications. Medication usage decreased by 5.3%, with a notable shift toward more expensive insulin use.
METHODOLOGY:
- Researchers conducted a retrospective cohort study using 2012-2020 prescription drug claims data from the TriNetX Diamond Network.
- A total of 129,997 individuals diagnosed with T2D were included, with claims observed both before and after age 65 years.
- The primary outcome was patient out-of-pocket costs for T2D drugs per quarter, adjusted to 2020 dollars.
- Drugs measured included biguanides (metformin), sulfonylureas, thiazolidinediones, insulin, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2 inhibitors), and amylin analogs, among others.
- Regression discontinuity design was used to examine the outcomes, adjusting for differential linear quarterly time trends, year fixed effects, and utilization composition and intensity.
TAKEAWAY:
- Reaching age 65 years was associated with an increase of $23.04 in mean quarterly out-of-pocket costs for T2D drugs (95% confidence interval [CI], $19.86-$26.22).
- The 95th percentile of out-of-pocket spending increased by $56.36 (95% CI, $51.48-$61.23) after utilization adjustment.
- T2D medication usage decreased by 5.3% at age 65 years, from 3.40 claims per quarter to 3.22 claims per quarter.
- Higher out-of-pockets were associated with insulin use, DPP-4 inhibitors, GLP-1s, and SGLT2 inhibitors.
IN PRACTICE:
“Our results have important implications for the provisions of the Inflation Reduction Act, many of which aim to reduce these costs. Reduced patient cost burden will improve adherence and the management of type 2 diabetes, likely leading to reductions in T2D complications,” wrote the authors of the study.
SOURCE:
The study was led by Douglas Barthold, PhD, Jing Li, MA, PhD, and Anirban Basu, MS, PhD, at the Comparative Health Outcomes, Policy, and Economics Institute, School of Pharmacy, University of Washington, Seattle. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s limitations include the possibility that not all claims of an individual were observed, as TriNetX claims data may not capture individuals who leave the healthcare system or have inaccurate or changing diagnoses. Additionally, the data lack individual-level insurance characteristics. The assumption that individuals transition to Medicare at age 65 years may not be true for all participants. The study also lacks clinical information regarding the severity of T2D, which could influence medication usage and out-of-pocket costs.
DISCLOSURES:
The study was supported by grants from the National Institute on Aging (NIA) and the University of Washington’s Population Health Initiative, Student Technology Fee program, and Provost’s office. Dr. Barthold and Dr. Li received grants from the NIA. Dr. Basu reported receiving personal fees from Salutis Consulting LLC outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Reaching age 65 years and enrolling in Medicare is associated with a $23 increase in quarterly out-of-pocket costs for type 2 diabetes (T2D) medications. Medication usage decreased by 5.3%, with a notable shift toward more expensive insulin use.
METHODOLOGY:
- Researchers conducted a retrospective cohort study using 2012-2020 prescription drug claims data from the TriNetX Diamond Network.
- A total of 129,997 individuals diagnosed with T2D were included, with claims observed both before and after age 65 years.
- The primary outcome was patient out-of-pocket costs for T2D drugs per quarter, adjusted to 2020 dollars.
- Drugs measured included biguanides (metformin), sulfonylureas, thiazolidinediones, insulin, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2 inhibitors), and amylin analogs, among others.
- Regression discontinuity design was used to examine the outcomes, adjusting for differential linear quarterly time trends, year fixed effects, and utilization composition and intensity.
TAKEAWAY:
- Reaching age 65 years was associated with an increase of $23.04 in mean quarterly out-of-pocket costs for T2D drugs (95% confidence interval [CI], $19.86-$26.22).
- The 95th percentile of out-of-pocket spending increased by $56.36 (95% CI, $51.48-$61.23) after utilization adjustment.
- T2D medication usage decreased by 5.3% at age 65 years, from 3.40 claims per quarter to 3.22 claims per quarter.
- Higher out-of-pockets were associated with insulin use, DPP-4 inhibitors, GLP-1s, and SGLT2 inhibitors.
IN PRACTICE:
“Our results have important implications for the provisions of the Inflation Reduction Act, many of which aim to reduce these costs. Reduced patient cost burden will improve adherence and the management of type 2 diabetes, likely leading to reductions in T2D complications,” wrote the authors of the study.
SOURCE:
The study was led by Douglas Barthold, PhD, Jing Li, MA, PhD, and Anirban Basu, MS, PhD, at the Comparative Health Outcomes, Policy, and Economics Institute, School of Pharmacy, University of Washington, Seattle. It was published online in JAMA Network Open.
LIMITATIONS:
The study’s limitations include the possibility that not all claims of an individual were observed, as TriNetX claims data may not capture individuals who leave the healthcare system or have inaccurate or changing diagnoses. Additionally, the data lack individual-level insurance characteristics. The assumption that individuals transition to Medicare at age 65 years may not be true for all participants. The study also lacks clinical information regarding the severity of T2D, which could influence medication usage and out-of-pocket costs.
DISCLOSURES:
The study was supported by grants from the National Institute on Aging (NIA) and the University of Washington’s Population Health Initiative, Student Technology Fee program, and Provost’s office. Dr. Barthold and Dr. Li received grants from the NIA. Dr. Basu reported receiving personal fees from Salutis Consulting LLC outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Tackling Inflammatory and Infectious Nail Disorders in Children
Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.
INFLAMMATORY NAIL DISORDERS
Nail Psoriasis
Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.1 Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).4
Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.5 Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).2 There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.
Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.16 Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.16
Nail Lichen Planus
Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.17 Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.5 Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.18
Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.19 In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).19 In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.20 In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.17 In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.16
Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.18
Trachyonychia
Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.23 Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.22,24
Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.24 Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.25 Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.26 Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.24
Nail Lichen Striatus
Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in isolation.27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.30
Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).31 Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.28
Nail AD
Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.32,33
Periungual inflammation from AD causes the nail changes.34 In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).35
Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.36 Anecdotally, most patients will improve with usual cutaneous AD management.
INFECTIOUS NAIL DISORDERS
Viral Infections
Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).37
Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.40 Onychomadesis is seen in 30% to 68% of patients with HFMD.37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.
Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.43 In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.44 In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.45
Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.44 It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.46 Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.
FUNGAL INFECTIONS
Onychomycosis
Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.47 Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.48 Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.
Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.51 Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.51
Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.52 Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).52 In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.53 In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efinaconazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).54
In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.55 Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.
BACTERIAL INFECTIONS
Acute Paronychia
Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.56 In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.57
Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.56
FINAL THOUGHTS
Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.
- Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207. doi:10.1111/pde.13402
- Plachouri KM, Mulita F, Georgiou S. Management of pediatric nail psoriasis. Cutis. 2021;108:292-294. doi:10.12788/cutis.0386
- Smith RJ, Rubin AI. Pediatric nail disorders: a review. Curr Opin Pediatr. 2020;32:506-515. doi:10.1097/mop.0000000000000921
- Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63. doi:10.1111/pde.13028
- Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112. doi:10.2165/11537110-000000000-00000
- Lee JYY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
- Nogueira M, Paller AS, Torres T. Targeted therapy for pediatric psoriasis. Paediatr Drugs. May 2021;23:203-212. doi:10.1007/s40272-021-00443-5
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. Updated August 16, 2023. Accessed July 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179. doi:10.1186/1752-1947-4-179
- Paller AS, Seyger MMB, Magariños GA, et al. Long-term efficacy and safety of up to 108 weeks of ixekizumab in pediatric patients with moderate to severe plaque psoriasis: the IXORA-PEDS randomized clinical trial. JAMA Dermatol. 2022;158:533-541. doi:10.1001/jamadermatol.2022.0655
- Diotallevi F, Simonetti O, Rizzetto G, et al. Biological treatments for pediatric psoriasis: state of the art and future perspectives. Int J Mol Sci. 2022;23:11128. doi:10.3390/ijms231911128
- Nash P, Mease PJ, Kirkham B, et al. Secukinumab provides sustained improvement in nail psoriasis, signs and symptoms of psoriatic arthritis and low rate of radiographic progression in patients with concomitant nail involvement: 2-year results from the Phase III FUTURE 5 study. Clin Exp Rheumatol. 2022;40:952-959. doi:10.55563/clinexprheumatol/3nuz51
- Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385. doi:10.1111/pde.13767
- Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriaticonycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. doi:10.1684/ejd.2015.2616
- Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352. doi:10.1159/000096202
- Iorizzo M, Gioia Di Chiacchio N, Di Chiacchio N, et al. Intralesional steroid injections for inflammatory nail dystrophies in the pediatric population. Pediatr Dermatol. 2023;40:759-761. doi:10.1111/pde.15295
- Tosti A, Piraccini BM, Cambiaghi S, et al. Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up. Arch Dermatol. 2001;137:1027-1032.
- Lipner SR. Nail lichen planus: a true nail emergency. J Am Acad Dermatol. 2019;80:e177-e178. doi:10.1016/j.jaad.2018.11.065
- Iorizzo M, Tosti A, Starace M, et al. Isolated nail lichen planus: an expert consensus on treatment of the classical form. J Am Acad Dermatol. 2020;83:1717-1723. doi:10.1016/j.jaad.2020.02.056
- Piraccini BM, Saccani E, Starace M, et al. Nail lichen planus: response to treatment and long term follow-up. Eur J Dermatol. 2010;20:489-496. doi:10.1684/ejd.2010.0952
- Mahajan R, Kaushik A, De D, et al. Pediatric trachyonychia- a retrospective study of 17 cases. Indian J Dermatol. 2021;66:689-690. doi:10.4103/ijd.ijd_42_21
- Leung AKC, Leong KF, Barankin B. Trachyonychia. J Pediatr. 2020;216:239-239.e1. doi:10.1016/j.jpeds.2019.08.034
- Haber JS, Chairatchaneeboon M, Rubin AI. Trachyonychia: review and update on clinical aspects, histology, and therapy. Skin Appendage Disord. 2017;2:109-115. doi:10.1159/000449063
- Jacobsen AA, Tosti A. Trachyonychia and twenty-nail dystrophy: a comprehensive review and discussion of diagnostic accuracy. Skin Appendage Disord. 2016;2:7-13. doi:10.1159/000445544
- Kumar MG, Ciliberto H, Bayliss SJ. Long-term follow-up of pediatric trachyonychia. Pediatr Dermatol. 2015;32:198-200. doi:10.1111/pde.12427
- Tosti A, Piraccini BM, Iorizzo M. Trachyonychia and related disorders: evaluation and treatment plans. Dermatolog Ther. 2002;15:121-125. doi:10.1046/j.1529-8019.2002.01511.x
- Leung AKC, Leong KF, Barankin B. Lichen striatus with nail involvement in a 6-year-old boy. Case Rep Pediatr. 2020;2020:1494760. doi:10.1155/2020/1494760
- Kim GW, Kim SH, Seo SH, et al. Lichen striatus with nail abnormality successfully treated with tacrolimus ointment. J Dermatol. 2009;36:616-617. doi:10.1111/j.1346-8138.2009.00720.x
- Iorizzo M, Rubin AI, Starace M. Nail lichen striatus: is dermoscopy useful for the diagnosis? Pediatr Dermatol. 2019;36:859-863. doi:10.1111/pde.13916
- Karp DL, Cohen BA. Onychodystrophy in lichen striatus. Pediatr Dermatol. 1993;10:359-361. doi:10.1111/j.1525-1470.1993.tb00399.x
- Tosti A, Peluso AM, Misciali C, et al. Nail lichen striatus: clinical features and long-term follow-up of five patients. J Am Acad Dermatol. 1997;36(6, pt 1):908-913. doi:10.1016/s0190-9622(97)80270-8
- Simpson EL, Thompson MM, Hanifin JM. Prevalence and morphology of hand eczema in patients with atopic dermatitis. Dermatitis. 2006;17:123-127. doi:10.2310/6620.2006.06005
- Sarifakioglu E, Yilmaz AE, Gorpelioglu C. Nail alterations in 250 infant patients: a clinical study. J Eur Acad Dermatol Venereol. 2008;22:741-744. doi:10.1111/j.1468-3083.2008.02592.x
- Milanesi N, D’Erme AM, Gola M. Nail improvement during alitretinoin treatment: three case reports and review of the literature. Clin Exp Dermatol. 2015;40:533-536. doi:10.1111/ced.12584
- Chung BY, Choi YW, Kim HO, et al. Nail dystrophy in patients with atopic dermatitis and its association with disease severity. Ann Dermatol. 2019;31:121-126. doi:10.5021/ad.2019.31.2.121
- Navarro-Triviño FJ, Vega-Castillo JJ, Ruiz-Villaverde R. Nail changes successfully treated with dupilumab in a patient with severe atopic dermatitis. Australas J Dermatol. 2021;62:e468-e469. doi:10.1111/ajd.13633
- Wei SH, Huang YP, Liu MC, et al. An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010. BMC Infect Dis. 2011;11:346. doi:10.1186/1471-2334-11-346
- Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26:280-283. doi:10.5021/ad.2014.26.2.280
- Verma S, Singal A. Nail changes in hand-foot-and-mouth disease (HFMD). Indian Dermatol Online J. 2021;12:656-657. doi:10.4103 /idoj.IDOJ_271_20
- Giordano LMC, de la Fuente LA, Lorca JMB, et al. Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents. Article in Spanish. Rev Chil Pediatr. 2018;89:380-383. doi:10.4067/s0370-41062018005000203
- Justino MCA, da SMD, Souza MF, et al. Atypical hand-foot-mouth disease in Belém, Amazon region, northern Brazil, with detection of coxsackievirus A6. J Clin Virol. 2020;126:104307. doi:10.1016/j.jcv.2020.104307
- Cheng FF, Zhang BB, Cao ML, et al. Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis. Transl Pediatr. 2022;11:1502-1509. doi:10.21037/tp-22-352
- Nagata S. Causes of Kawasaki disease-from past to present. Front Pediatr. 2019;7:18. doi:10.3389/fped.2019.00018
- Mitsuishi T, Miyata K, Ando A, et al. Characteristic nail lesions in Kawasaki disease: case series and literature review. J Dermatol. 2022;49:232-238. doi:10.1111/1346-8138.16276
- Lindsley CB. Nail-bed lines in Kawasaki disease. Am J Dis Child. 1992;146:659-660. doi:10.1001/archpedi.1992.02160180017005
- Matsumura O, Nakagishi Y. Pincer nails upon convalescence from Kawasaki disease. J Pediatr. 2022;246:279. doi:10.1016/j.jpeds.2022.03.002
- Solís-Arias MP, García-Romero MT. Onychomycosis in children. a review. Int J Dermatol. 2017;56:123-130. doi:10.1111/ijd.13392
- Gupta AK, Mays RR, Versteeg SG, et al. Onychomycosis in children: safety and efficacy of antifungal agents. Pediatr Dermatol. 2018;35:552-559. doi:10.1111/pde.13561
- 49. Gupta AK, Venkataraman M, Shear NH, et al. Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis. Dermatol Ther. 2020;33:e13613. doi:10.1111/dth.13613
- Falotico JM, Lipner SR. Updated perspectives on the diagnosis and management of onychomycosis. Clin Cosmet Investig Dermatol. 2022;15:1933-1957. doi:10.2147/ccid.S362635
- Patel D, Castelo-Soccio LA, Rubin AI, et al. Laboratory monitoring during systemic terbinafine therapy for pediatric onychomycosis. JAMA Dermatol. 2017;153:1326-1327. doi:10.1001/jamadermatol.2017.4483
- Friedlander SF, Chan YC, Chan YH, et al. Onychomycosis does not always require systemic treatment for cure: a trial using topical therapy. Pediatr Dermatol. 2013;30:316-322. doi:10.1111/pde.12064
- Rich P, Spellman M, Purohit V, et al. Tavaborole 5% topical solution for the treatment of toenail onychomycosis in pediatric patients: results from a phase 4 open-label study. J Drugs Dermatol. 2019;18:190-195.
- Gupta AK, Venkataraman M, Abramovits W, et al. JUBLIA (efinaconazole 10% solution) in the treatment of pediatric onychomycosis. Skinmed. 2021;19:206-210.
- Gupta AK, Paquet M. Systemic antifungals to treat onychomycosis in children: a systematic review. Pediatr Dermatol. 2013;30:294-302. doi:10.1111/pde.12048
- Leggit JC. Acute and chronic paronychia. Am Fam Physician. 2017;96:44-51.
- Lipner SR, Scher RK. Congenital malalignment of the great toenails with acute paronychia. Pediatr Dermatol. 2016;33:e288-e289.doi:10.1111/pde.12924
Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.
INFLAMMATORY NAIL DISORDERS
Nail Psoriasis
Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.1 Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).4
Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.5 Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).2 There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.
Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.16 Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.16
Nail Lichen Planus
Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.17 Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.5 Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.18
Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.19 In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).19 In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.20 In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.17 In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.16
Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.18
Trachyonychia
Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.23 Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.22,24
Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.24 Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.25 Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.26 Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.24
Nail Lichen Striatus
Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in isolation.27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.30
Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).31 Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.28
Nail AD
Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.32,33
Periungual inflammation from AD causes the nail changes.34 In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).35
Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.36 Anecdotally, most patients will improve with usual cutaneous AD management.
INFECTIOUS NAIL DISORDERS
Viral Infections
Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).37
Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.40 Onychomadesis is seen in 30% to 68% of patients with HFMD.37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.
Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.43 In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.44 In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.45
Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.44 It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.46 Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.
FUNGAL INFECTIONS
Onychomycosis
Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.47 Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.48 Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.
Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.51 Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.51
Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.52 Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).52 In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.53 In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efinaconazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).54
In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.55 Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.
BACTERIAL INFECTIONS
Acute Paronychia
Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.56 In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.57
Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.56
FINAL THOUGHTS
Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.
Nail disorders are common among pediatric patients but often are underdiagnosed or misdiagnosed because of their unique disease manifestations. These conditions may severely impact quality of life. There are few nail disease clinical trials that include children. Consequently, most treatment recommendations are based on case series and expert consensus recommendations. We review inflammatory and infectious nail disorders in pediatric patients. By describing characteristics, clinical manifestations, and management approaches for these conditions, we aim to provide guidance to dermatologists in their diagnosis and treatment.
INFLAMMATORY NAIL DISORDERS
Nail Psoriasis
Nail involvement in children with psoriasis is common, with prevalence estimates ranging from 17% to 39.2%.1 Nail matrix psoriasis may manifest with pitting (large irregular pits) and leukonychia as well as chromonychia and nail plate crumbling. Onycholysis, oil drop spots (salmon patches), and subungual hyperkeratosis can be seen in nail bed psoriasis. Nail pitting is the most frequently observed clinical finding (Figure 1).2,3 In a cross-sectional multicenter study of 313 children with cutaneous psoriasis in France, nail findings were present in 101 patients (32.3%). There were associations between nail findings and presence of psoriatic arthritis (P=.03), palmoplantar psoriasis (P<.001), and severity of psoriatic disease, defined as use of systemic treatment with phototherapy (psoralen plus UVA, UVB), traditional systemic treatment (acitretin, methotrexate, cyclosporine), or a biologic (P=.003).4
Topical steroids and vitamin D analogues may be used with or without occlusion and may be efficacious.5 Several case reports describe systemic treatments for psoriasis in children, including methotrexate, acitretin, and apremilast (approved for children 6 years and older for plaque psoriasis by the US Food and Drug Administration [FDA]).2 There are 5 biologic drugs currently approved for the treatment of pediatric psoriasis—adalimumab, etanercept, ustekinumab, secukinumab, ixekizumab—and 6 drugs currently undergoing phase 3 studies—brodalumab, guselkumab, risankizumab, tildrakizumab, certolizumab pegol, and deucravacitinib (Table 1).6-15 Adalimumab is specifically approved for moderate to severe nail psoriasis in adults 18 years and older.
Intralesional steroid injections are sometimes useful in the management of nail matrix psoriasis; however, appropriate patient selection is critical due to the pain associated with the procedure. In a prospective study of 16 children (age range, 9–17 years) with nail psoriasis treated with intralesional triamcinolone (ILTAC) 2.5 to 5 mg/mL every 4 to 8 weeks for a minimum of 3 to 6 months, 9 patients achieved resolution and 6 had improvement of clinical findings.16 Local adverse events were mild, including injection-site pain (66%), subungual hematoma (n=1), Beau lines (n=1), proximal nail fold hypopigmentation (n=2), and proximal nail fold atrophy (n=2). Because the proximal nail fold in children is thinner than in adults, there may be an increased risk for nail fold hypopigmentation and atrophy in children. Therefore, a maximum ILTAC concentration of 2.5 mg/mL with 0.2 mL maximum volume per nail per session is recommended for children younger than 15 years.16
Nail Lichen Planus
Nail lichen planus (NLP) is uncommon in children, with few biopsy-proven cases documented in the literature.17 Common clinical findings are onychorrhexis, nail plate thinning, fissuring, splitting, and atrophy with koilonychia.5 Although pterygium development (irreversible nail matrix scarring) is uncommon in pediatric patients, NLP can be progressive and may cause irreversible destruction of the nail matrix and subsequent nail loss, warranting therapeutic intervention.18
Treatment of NLP may be difficult, as there are no options that work in all patients. Current literature supports the use of systemic corticosteroids or ILTAC for the treatment of NLP; however, recurrence rates can be high. According to an expert consensus paper on NLP treatment, ILTAC may be injected in a concentration of 2.5, 5, or 10 mg/mL according to disease severity.19 In severe or resistant cases, intramuscular (IM) triamcinolone may be considered, especially if more than 3 nails are affected. A dosage of 0.5 to 1 mg/kg/mo for at least 3 to 6 months is recommended for both children and adults, with 1 mg/kg/mo recommended in the active treatment phase (first 2–3 months).19 In a retrospective review of 5 pediatric patients with NLP treated with IM triamcinolone 0.5 mg/kg/mo, 3 patients had resolution and 2 improved with treatment.20 In a prospective study of 10 children with NLP, IM triamcinolone at a dosage of 0.5 to 1 mg/kg every 30 days for 3 to 6 months resulted in resolution of nail findings in 9 patients.17 In a prospective study of 14 pediatric patients with NLP treated with 2.5 to 5 mg/mL of ILTAC, 10 achieved resolution and 3 improved.16
Intralesional triamcinolone injections may be better suited for teenagers compared to younger children who may be more apprehensive of needles. To minimize pain, it is recommended to inject ILTAC slowly at room temperature, with use of “talkesthesia” and vibration devices, 1% lidocaine, or ethyl chloride spray.18
Trachyonychia
Trachyonychia is characterized by the presence of sandpaperlike nails. It manifests with brittle thin nails with longitudinal ridging, onychoschizia, and thickened hyperkeratotic cuticles. Trachyonychia typically involves multiple nails, with a peak age of onset between 3 and 12 years.21,22 There are 2 variants: the opaque type with rough longitudinal ridging, and the shiny variant with opalescent nails and pits that reflect light. The opaque variant is more common and is associated with psoriasis, whereas the shiny variant is less common and is associated with alopecia areata.23 Although most cases are idiopathic, some are associated with psoriasis and alopecia areata, as previously noted, as well as atopic dermatitis (AD) and lichen planus.22,24
Fortunately, trachyonychia does not lead to permanent nail damage or pterygium, making treatment primarily focused on addressing functional and cosmetic concerns.24 Spontaneous resolution occurs in approximately 50% of patients. In a prospective study of 11 patients with idiopathic trachyonychia, there was partial improvement in 5 of 9 patients treated with topical steroids, 1 with only petrolatum, and 1 with vitamin supplements. Complete resolution was reported in 1 patient treated with topical steroids.25 Because trachyonychia often is self-resolving, no treatment is required and a conservative approach is strongly recommended.26 Treatment options include topical corticosteroids, tazarotene, and 5-fluorouracil. Intralesional triamcinolone, systemic cyclosporine, retinoids, systemic corticosteroids, and tofacitinib have been described in case reports, though none of these have been shown to be 100% efficacious.24
Nail Lichen Striatus
Lichen striatus involving the nail is uncommon and is characterized by onycholysis, longitudinal ridging, splitting, and fraying, as well as what appears to be a subungual tumor. It can encompass the entire nail or may be isolated to a portion of the nail (Figure 2). Usually, a Blaschko-linear array of flesh-colored papules on the more proximal digit directly adjacent to the nail dystrophy will be seen, though nail findings can occur in isolation.27-29 The underlying pathophysiology is not clear; however, one hypothesis is that a triggering event, such as trauma, induces the expression of antigens that elicit a self-limiting immune-mediated response by CD8 T lymphocytes.30
Generally, nail lichen striatus spontaneously resolves in 1 to 2 years without treatment. In a prospective study of 5 patients with nail lichen striatus, the median time to resolution was 22.6 months (range, 10–30 months).31 Topical steroids may be used for pruritus. In one case report, a 3-year-old boy with nail lichen striatus of 4 months’ duration was treated with tacrolimus ointment 0.03% daily for 3 months.28
Nail AD
Nail changes with AD may be more common in adults than children or are underreported. In a study of 777 adults with AD, nail dystrophy was present in 124 patients (16%), whereas in a study of 250 pediatric patients with AD (aged 0-2 years), nail dystrophy was present in only 4 patients.32,33
Periungual inflammation from AD causes the nail changes.34 In a cross-sectional study of 24 pediatric patients with nail dystrophy due to AD, transverse grooves (Beau lines) were present in 25% (6/24), nail pitting in 16.7% (4/24), koilonychia in 16.7% (4/24), trachyonychia in 12.5% (3/24), leukonychia in 12.5% (3/24), brachyonychia in 8.3% (2/24), melanonychia in 8.3% (2/24), onychomadesis in 8.3% (2/24), onychoschizia in 8.3% (2/24), and onycholysis in 8.3% (2/24). There was an association between disease severity and presence of toenail dystrophy (P=.03).35
Topical steroids with or without occlusion can be used to treat nail changes. Although there is limited literature describing the treatment of nail AD in children, a 61-year-old man with nail changes associated with AD achieved resolution with 3 months of treatment with dupilumab.36 Anecdotally, most patients will improve with usual cutaneous AD management.
INFECTIOUS NAIL DISORDERS
Viral Infections
Hand, Foot, and Mouth Disease—Hand, foot, and mouth disease (HFMD) is a common childhood viral infection caused by various enteroviruses, most commonly coxsackievirus A16, with the A6 variant causing more severe disease. Fever and painful vesicles involving the oral mucosa as well as palms and soles give the disease its name. Nail changes are common. In a prospective study involving 130 patients with laboratory-confirmed coxsackievirus CA6 serotype infection, 37% developed onychomadesis vs only 5% of 145 cases with non-CA6 enterovirus infection who developed nail findings. There was an association between CA6 infection and presence of nail changes (P<.001).37
Findings ranging from transverse grooves (Beau lines) to complete nail shedding (onychomadesis)(Figure 3) may be seen.38,39 Nail findings in HFMD are due to transient inhibition of nail growth and present approximately 3 to 6 weeks after infection.40 Onychomadesis is seen in 30% to 68% of patients with HFMD.37,41,42 Nail findings in HFMD spontaneously resolve with nail growth (2–3 mm per month for fingernails and 1 mm per month for toenails) and do not require specific treatment. Although the appearance of nail changes associated with HFMD can be disturbing, dermatologists can reassure children and their parents that the nails will resolve with the next cycle of growth.
Kawasaki Disease—Kawasaki disease (KD) is a vasculitis primarily affecting children and infants. Although the specific pathogen and pathophysiology is not entirely clear, clinical observations have suggested an infectious cause, most likely a virus.43 In Japan, more than 15,000 cases of KD are documented annually, while approximately 4200 cases are seen in the United States.44 In a prospective study from 1984 to 1990, 4 of 26 (15.4%) patients with KD presented with nail manifestations during the late acute phase or early convalescent phase of disease. There were no significant associations between nail dystrophy and severity of KD, such as coronary artery aneurysm.45
Nail changes reported in children with KD include onychomadesis, onycholysis, orange-brown chromonychia, splinter hemorrhages, Beau lines, and pincer nails. In a review of nail changes associated with KD from 1980 to 2021, orange-brown transverse chromonychia, which may evolve into transverse leukonychia, was the most common nail finding reported, occurring in 17 of 31 (54.8%) patients.44 It has been hypothesized that nail changes may result from blood flow disturbance due to the underlying vasculitis.46 Nail changes appear several weeks after the onset of fever and are self-limited. Resolution occurs with nail growth, with no treatment required.
FUNGAL INFECTIONS
Onychomycosis
Onychomycosis is a fungal infection of the nails that occurs in 0.2% to 5.5% of pediatric patients, and its prevalence may be increasing, which may be due to environmental factors or increased rates of diabetes mellitus and obesity in the pediatric population.47 Onychomycosis represents 15.5% of nail dystrophies in pediatric patients.48 Some dermatologists treat presumptive onychomycosis without confirmation; however, we do not recommend that approach. Because the differential is broad and the duration of treatment is long, mycologic examination (potassium hydroxide preparation, fungal culture, polymerase chain reaction, and/or histopathology) should be obtained to confirm onychomycosis prior to initiation of antifungal management. Family members of affected individuals should be evaluated and treated, if indicated, for onychomycosis and tinea pedis, as household transmission is common.
Currently, there are 2 topical FDA-approved treatments for pediatric onychomycosis in children 6 years and older (Table 2).49,50 There is a discussion of the need for confirmatory testing for onychomycosis in children, particularly when systemic treatment is prescribed. In a retrospective review of 269 pediatric patients with onychomycosis prescribed terbinafine, 53.5% (n=144) underwent laboratory monitoring of liver function and complete blood cell counts, and 12.5% had grade 1 laboratory abnormalities either prior to (12/144 [8.3%]) or during (6/144 [4.2%]) therapy.51 Baseline transaminase monitoring is recommended, though subsequent routine laboratory monitoring in healthy children may have limited utility with associated increased costs, incidental findings, and patient discomfort and likely is not needed.51
Pediatric onychomycosis responds better to topical therapy than adult disease, and pediatric patients do not always require systemic treatment.52 Ciclopirox is not FDA approved for the treatment of pediatric onychomycosis, but in a 32-week clinical trial of ciclopirox lacquer 8% use in 40 patients, 77% (27/35) of treated patients achieved mycologic cure. Overall, 71% of treated patients (25/35) vs 22% (2/9) of controls achieved efficacy (defined as investigator global assessment score of 2 or lower).52 In an open-label, single-arm clinical trial assessing tavaborole solution 5% applied once daily for 48 weeks for the treatment of toenail onychomycosis in pediatric patients (aged 6–17 years), 36.2% (20/55) of patients achieved mycologic cure, and 8.5% (5/55) achieved complete cure at week 52 with mild or minimal adverse effects.53 In an open-label, phase 4 study of the safety and efficacy of efinaconazole solution 10% applied once daily for 48 weeks in pediatric patients (aged 6 to 16 years) (n=60), 65% (35/60) achieved mycologic cure, 42% (25/60) achieved clinical cure, and 40% (24/60) achieved complete cure at 52 weeks. The most common adverse effects of efinaconazole were local and included ingrown toenail (1/60), application-site dermatitis (1/60), application-site vesicles (1/60), and application-site pain (1/60).54
In a systematic review of systemic antifungals for onychomycosis in 151 pediatric patients, itraconazole, fluconazole, griseofulvin, and terbinafine resulted in complete cure rates similar to those of the adult population, with excellent safety profiles.55 Depending on the situation, initiation of treatment with topical medications followed by addition of systemic antifungal agents only if needed may be an appropriate course of action.
BACTERIAL INFECTIONS
Acute Paronychia
Acute paronychia is a nail-fold infection that develops after the protective nail barrier has been compromised.56 In children, thumb-sucking, nail-biting, frequent oral manipulation of the digits, and poor skin hygiene are risk factors. Acute paronychia also may develop in association with congenital malalignment of the great toenails.57
Clinical manifestations include localized pain, erythema, and nail fold edema (Figure 4). Purulent material and abscess formation may ensue. Staphylococcus aureus as well as methicillin-resistant S aureus and Streptococcus pyogenes are classically the most common causes of acute paronychia. Treatment of paronychia is based on severity. In mild cases, warm soaks with topical antibiotics are indicated. Oral antibiotics should be prescribed for more severe presentations. If there is no improvement after 48 hours, surgical drainage is required to facilitate healing.56
FINAL THOUGHTS
Inflammatory and infectious nail disorders in children are relatively common and may impact the physical and emotional well-being of young patients. By understanding the distinctive features of these nail disorders in pediatric patients, dermatologists can provide anticipatory guidance and informed treatment options to children and their parents. Further research is needed to expand our understanding of pediatric nail disorders and create targeted therapeutic interventions, particularly for NLP and psoriasis.
- Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207. doi:10.1111/pde.13402
- Plachouri KM, Mulita F, Georgiou S. Management of pediatric nail psoriasis. Cutis. 2021;108:292-294. doi:10.12788/cutis.0386
- Smith RJ, Rubin AI. Pediatric nail disorders: a review. Curr Opin Pediatr. 2020;32:506-515. doi:10.1097/mop.0000000000000921
- Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63. doi:10.1111/pde.13028
- Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112. doi:10.2165/11537110-000000000-00000
- Lee JYY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
- Nogueira M, Paller AS, Torres T. Targeted therapy for pediatric psoriasis. Paediatr Drugs. May 2021;23:203-212. doi:10.1007/s40272-021-00443-5
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. Updated August 16, 2023. Accessed July 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179. doi:10.1186/1752-1947-4-179
- Paller AS, Seyger MMB, Magariños GA, et al. Long-term efficacy and safety of up to 108 weeks of ixekizumab in pediatric patients with moderate to severe plaque psoriasis: the IXORA-PEDS randomized clinical trial. JAMA Dermatol. 2022;158:533-541. doi:10.1001/jamadermatol.2022.0655
- Diotallevi F, Simonetti O, Rizzetto G, et al. Biological treatments for pediatric psoriasis: state of the art and future perspectives. Int J Mol Sci. 2022;23:11128. doi:10.3390/ijms231911128
- Nash P, Mease PJ, Kirkham B, et al. Secukinumab provides sustained improvement in nail psoriasis, signs and symptoms of psoriatic arthritis and low rate of radiographic progression in patients with concomitant nail involvement: 2-year results from the Phase III FUTURE 5 study. Clin Exp Rheumatol. 2022;40:952-959. doi:10.55563/clinexprheumatol/3nuz51
- Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385. doi:10.1111/pde.13767
- Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriaticonycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. doi:10.1684/ejd.2015.2616
- Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352. doi:10.1159/000096202
- Iorizzo M, Gioia Di Chiacchio N, Di Chiacchio N, et al. Intralesional steroid injections for inflammatory nail dystrophies in the pediatric population. Pediatr Dermatol. 2023;40:759-761. doi:10.1111/pde.15295
- Tosti A, Piraccini BM, Cambiaghi S, et al. Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up. Arch Dermatol. 2001;137:1027-1032.
- Lipner SR. Nail lichen planus: a true nail emergency. J Am Acad Dermatol. 2019;80:e177-e178. doi:10.1016/j.jaad.2018.11.065
- Iorizzo M, Tosti A, Starace M, et al. Isolated nail lichen planus: an expert consensus on treatment of the classical form. J Am Acad Dermatol. 2020;83:1717-1723. doi:10.1016/j.jaad.2020.02.056
- Piraccini BM, Saccani E, Starace M, et al. Nail lichen planus: response to treatment and long term follow-up. Eur J Dermatol. 2010;20:489-496. doi:10.1684/ejd.2010.0952
- Mahajan R, Kaushik A, De D, et al. Pediatric trachyonychia- a retrospective study of 17 cases. Indian J Dermatol. 2021;66:689-690. doi:10.4103/ijd.ijd_42_21
- Leung AKC, Leong KF, Barankin B. Trachyonychia. J Pediatr. 2020;216:239-239.e1. doi:10.1016/j.jpeds.2019.08.034
- Haber JS, Chairatchaneeboon M, Rubin AI. Trachyonychia: review and update on clinical aspects, histology, and therapy. Skin Appendage Disord. 2017;2:109-115. doi:10.1159/000449063
- Jacobsen AA, Tosti A. Trachyonychia and twenty-nail dystrophy: a comprehensive review and discussion of diagnostic accuracy. Skin Appendage Disord. 2016;2:7-13. doi:10.1159/000445544
- Kumar MG, Ciliberto H, Bayliss SJ. Long-term follow-up of pediatric trachyonychia. Pediatr Dermatol. 2015;32:198-200. doi:10.1111/pde.12427
- Tosti A, Piraccini BM, Iorizzo M. Trachyonychia and related disorders: evaluation and treatment plans. Dermatolog Ther. 2002;15:121-125. doi:10.1046/j.1529-8019.2002.01511.x
- Leung AKC, Leong KF, Barankin B. Lichen striatus with nail involvement in a 6-year-old boy. Case Rep Pediatr. 2020;2020:1494760. doi:10.1155/2020/1494760
- Kim GW, Kim SH, Seo SH, et al. Lichen striatus with nail abnormality successfully treated with tacrolimus ointment. J Dermatol. 2009;36:616-617. doi:10.1111/j.1346-8138.2009.00720.x
- Iorizzo M, Rubin AI, Starace M. Nail lichen striatus: is dermoscopy useful for the diagnosis? Pediatr Dermatol. 2019;36:859-863. doi:10.1111/pde.13916
- Karp DL, Cohen BA. Onychodystrophy in lichen striatus. Pediatr Dermatol. 1993;10:359-361. doi:10.1111/j.1525-1470.1993.tb00399.x
- Tosti A, Peluso AM, Misciali C, et al. Nail lichen striatus: clinical features and long-term follow-up of five patients. J Am Acad Dermatol. 1997;36(6, pt 1):908-913. doi:10.1016/s0190-9622(97)80270-8
- Simpson EL, Thompson MM, Hanifin JM. Prevalence and morphology of hand eczema in patients with atopic dermatitis. Dermatitis. 2006;17:123-127. doi:10.2310/6620.2006.06005
- Sarifakioglu E, Yilmaz AE, Gorpelioglu C. Nail alterations in 250 infant patients: a clinical study. J Eur Acad Dermatol Venereol. 2008;22:741-744. doi:10.1111/j.1468-3083.2008.02592.x
- Milanesi N, D’Erme AM, Gola M. Nail improvement during alitretinoin treatment: three case reports and review of the literature. Clin Exp Dermatol. 2015;40:533-536. doi:10.1111/ced.12584
- Chung BY, Choi YW, Kim HO, et al. Nail dystrophy in patients with atopic dermatitis and its association with disease severity. Ann Dermatol. 2019;31:121-126. doi:10.5021/ad.2019.31.2.121
- Navarro-Triviño FJ, Vega-Castillo JJ, Ruiz-Villaverde R. Nail changes successfully treated with dupilumab in a patient with severe atopic dermatitis. Australas J Dermatol. 2021;62:e468-e469. doi:10.1111/ajd.13633
- Wei SH, Huang YP, Liu MC, et al. An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010. BMC Infect Dis. 2011;11:346. doi:10.1186/1471-2334-11-346
- Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26:280-283. doi:10.5021/ad.2014.26.2.280
- Verma S, Singal A. Nail changes in hand-foot-and-mouth disease (HFMD). Indian Dermatol Online J. 2021;12:656-657. doi:10.4103 /idoj.IDOJ_271_20
- Giordano LMC, de la Fuente LA, Lorca JMB, et al. Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents. Article in Spanish. Rev Chil Pediatr. 2018;89:380-383. doi:10.4067/s0370-41062018005000203
- Justino MCA, da SMD, Souza MF, et al. Atypical hand-foot-mouth disease in Belém, Amazon region, northern Brazil, with detection of coxsackievirus A6. J Clin Virol. 2020;126:104307. doi:10.1016/j.jcv.2020.104307
- Cheng FF, Zhang BB, Cao ML, et al. Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis. Transl Pediatr. 2022;11:1502-1509. doi:10.21037/tp-22-352
- Nagata S. Causes of Kawasaki disease-from past to present. Front Pediatr. 2019;7:18. doi:10.3389/fped.2019.00018
- Mitsuishi T, Miyata K, Ando A, et al. Characteristic nail lesions in Kawasaki disease: case series and literature review. J Dermatol. 2022;49:232-238. doi:10.1111/1346-8138.16276
- Lindsley CB. Nail-bed lines in Kawasaki disease. Am J Dis Child. 1992;146:659-660. doi:10.1001/archpedi.1992.02160180017005
- Matsumura O, Nakagishi Y. Pincer nails upon convalescence from Kawasaki disease. J Pediatr. 2022;246:279. doi:10.1016/j.jpeds.2022.03.002
- Solís-Arias MP, García-Romero MT. Onychomycosis in children. a review. Int J Dermatol. 2017;56:123-130. doi:10.1111/ijd.13392
- Gupta AK, Mays RR, Versteeg SG, et al. Onychomycosis in children: safety and efficacy of antifungal agents. Pediatr Dermatol. 2018;35:552-559. doi:10.1111/pde.13561
- 49. Gupta AK, Venkataraman M, Shear NH, et al. Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis. Dermatol Ther. 2020;33:e13613. doi:10.1111/dth.13613
- Falotico JM, Lipner SR. Updated perspectives on the diagnosis and management of onychomycosis. Clin Cosmet Investig Dermatol. 2022;15:1933-1957. doi:10.2147/ccid.S362635
- Patel D, Castelo-Soccio LA, Rubin AI, et al. Laboratory monitoring during systemic terbinafine therapy for pediatric onychomycosis. JAMA Dermatol. 2017;153:1326-1327. doi:10.1001/jamadermatol.2017.4483
- Friedlander SF, Chan YC, Chan YH, et al. Onychomycosis does not always require systemic treatment for cure: a trial using topical therapy. Pediatr Dermatol. 2013;30:316-322. doi:10.1111/pde.12064
- Rich P, Spellman M, Purohit V, et al. Tavaborole 5% topical solution for the treatment of toenail onychomycosis in pediatric patients: results from a phase 4 open-label study. J Drugs Dermatol. 2019;18:190-195.
- Gupta AK, Venkataraman M, Abramovits W, et al. JUBLIA (efinaconazole 10% solution) in the treatment of pediatric onychomycosis. Skinmed. 2021;19:206-210.
- Gupta AK, Paquet M. Systemic antifungals to treat onychomycosis in children: a systematic review. Pediatr Dermatol. 2013;30:294-302. doi:10.1111/pde.12048
- Leggit JC. Acute and chronic paronychia. Am Fam Physician. 2017;96:44-51.
- Lipner SR, Scher RK. Congenital malalignment of the great toenails with acute paronychia. Pediatr Dermatol. 2016;33:e288-e289.doi:10.1111/pde.12924
- Uber M, Carvalho VO, Abagge KT, et al. Clinical features and nail clippings in 52 children with psoriasis. Pediatr Dermatol. 2018;35:202-207. doi:10.1111/pde.13402
- Plachouri KM, Mulita F, Georgiou S. Management of pediatric nail psoriasis. Cutis. 2021;108:292-294. doi:10.12788/cutis.0386
- Smith RJ, Rubin AI. Pediatric nail disorders: a review. Curr Opin Pediatr. 2020;32:506-515. doi:10.1097/mop.0000000000000921
- Pourchot D, Bodemer C, Phan A, et al. Nail psoriasis: a systematic evaluation in 313 children with psoriasis. Pediatr Dermatol. 2017;34:58-63. doi:10.1111/pde.13028
- Richert B, André J. Nail disorders in children: diagnosis and management. Am J Clin Dermatol. 2011;12:101-112. doi:10.2165/11537110-000000000-00000
- Lee JYY. Severe 20-nail psoriasis successfully treated by low dose methotrexate. Dermatol Online J. 2009;15:8.
- Nogueira M, Paller AS, Torres T. Targeted therapy for pediatric psoriasis. Paediatr Drugs. May 2021;23:203-212. doi:10.1007/s40272-021-00443-5
- Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet]. Updated August 16, 2023. Accessed July 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556114/
- Teran CG, Teran-Escalera CN, Balderrama C. A severe case of erythrodermic psoriasis associated with advanced nail and joint manifestations: a case report. J Med Case Rep. 2010;4:179. doi:10.1186/1752-1947-4-179
- Paller AS, Seyger MMB, Magariños GA, et al. Long-term efficacy and safety of up to 108 weeks of ixekizumab in pediatric patients with moderate to severe plaque psoriasis: the IXORA-PEDS randomized clinical trial. JAMA Dermatol. 2022;158:533-541. doi:10.1001/jamadermatol.2022.0655
- Diotallevi F, Simonetti O, Rizzetto G, et al. Biological treatments for pediatric psoriasis: state of the art and future perspectives. Int J Mol Sci. 2022;23:11128. doi:10.3390/ijms231911128
- Nash P, Mease PJ, Kirkham B, et al. Secukinumab provides sustained improvement in nail psoriasis, signs and symptoms of psoriatic arthritis and low rate of radiographic progression in patients with concomitant nail involvement: 2-year results from the Phase III FUTURE 5 study. Clin Exp Rheumatol. 2022;40:952-959. doi:10.55563/clinexprheumatol/3nuz51
- Wells LE, Evans T, Hilton R, et al. Use of secukinumab in a pediatric patient leads to significant improvement in nail psoriasis and psoriatic arthritis. Pediatr Dermatol. 2019;36:384-385. doi:10.1111/pde.13767
- Watabe D, Endoh K, Maeda F, et al. Childhood-onset psoriaticonycho-pachydermo-periostitis treated successfully with infliximab. Eur J Dermatol. 2015;25:506-508. doi:10.1684/ejd.2015.2616
- Pereira TM, Vieira AP, Fernandes JC, et al. Anti-TNF-alpha therapy in childhood pustular psoriasis. Dermatology. 2006;213:350-352. doi:10.1159/000096202
- Iorizzo M, Gioia Di Chiacchio N, Di Chiacchio N, et al. Intralesional steroid injections for inflammatory nail dystrophies in the pediatric population. Pediatr Dermatol. 2023;40:759-761. doi:10.1111/pde.15295
- Tosti A, Piraccini BM, Cambiaghi S, et al. Nail lichen planus in children: clinical features, response to treatment, and long-term follow-up. Arch Dermatol. 2001;137:1027-1032.
- Lipner SR. Nail lichen planus: a true nail emergency. J Am Acad Dermatol. 2019;80:e177-e178. doi:10.1016/j.jaad.2018.11.065
- Iorizzo M, Tosti A, Starace M, et al. Isolated nail lichen planus: an expert consensus on treatment of the classical form. J Am Acad Dermatol. 2020;83:1717-1723. doi:10.1016/j.jaad.2020.02.056
- Piraccini BM, Saccani E, Starace M, et al. Nail lichen planus: response to treatment and long term follow-up. Eur J Dermatol. 2010;20:489-496. doi:10.1684/ejd.2010.0952
- Mahajan R, Kaushik A, De D, et al. Pediatric trachyonychia- a retrospective study of 17 cases. Indian J Dermatol. 2021;66:689-690. doi:10.4103/ijd.ijd_42_21
- Leung AKC, Leong KF, Barankin B. Trachyonychia. J Pediatr. 2020;216:239-239.e1. doi:10.1016/j.jpeds.2019.08.034
- Haber JS, Chairatchaneeboon M, Rubin AI. Trachyonychia: review and update on clinical aspects, histology, and therapy. Skin Appendage Disord. 2017;2:109-115. doi:10.1159/000449063
- Jacobsen AA, Tosti A. Trachyonychia and twenty-nail dystrophy: a comprehensive review and discussion of diagnostic accuracy. Skin Appendage Disord. 2016;2:7-13. doi:10.1159/000445544
- Kumar MG, Ciliberto H, Bayliss SJ. Long-term follow-up of pediatric trachyonychia. Pediatr Dermatol. 2015;32:198-200. doi:10.1111/pde.12427
- Tosti A, Piraccini BM, Iorizzo M. Trachyonychia and related disorders: evaluation and treatment plans. Dermatolog Ther. 2002;15:121-125. doi:10.1046/j.1529-8019.2002.01511.x
- Leung AKC, Leong KF, Barankin B. Lichen striatus with nail involvement in a 6-year-old boy. Case Rep Pediatr. 2020;2020:1494760. doi:10.1155/2020/1494760
- Kim GW, Kim SH, Seo SH, et al. Lichen striatus with nail abnormality successfully treated with tacrolimus ointment. J Dermatol. 2009;36:616-617. doi:10.1111/j.1346-8138.2009.00720.x
- Iorizzo M, Rubin AI, Starace M. Nail lichen striatus: is dermoscopy useful for the diagnosis? Pediatr Dermatol. 2019;36:859-863. doi:10.1111/pde.13916
- Karp DL, Cohen BA. Onychodystrophy in lichen striatus. Pediatr Dermatol. 1993;10:359-361. doi:10.1111/j.1525-1470.1993.tb00399.x
- Tosti A, Peluso AM, Misciali C, et al. Nail lichen striatus: clinical features and long-term follow-up of five patients. J Am Acad Dermatol. 1997;36(6, pt 1):908-913. doi:10.1016/s0190-9622(97)80270-8
- Simpson EL, Thompson MM, Hanifin JM. Prevalence and morphology of hand eczema in patients with atopic dermatitis. Dermatitis. 2006;17:123-127. doi:10.2310/6620.2006.06005
- Sarifakioglu E, Yilmaz AE, Gorpelioglu C. Nail alterations in 250 infant patients: a clinical study. J Eur Acad Dermatol Venereol. 2008;22:741-744. doi:10.1111/j.1468-3083.2008.02592.x
- Milanesi N, D’Erme AM, Gola M. Nail improvement during alitretinoin treatment: three case reports and review of the literature. Clin Exp Dermatol. 2015;40:533-536. doi:10.1111/ced.12584
- Chung BY, Choi YW, Kim HO, et al. Nail dystrophy in patients with atopic dermatitis and its association with disease severity. Ann Dermatol. 2019;31:121-126. doi:10.5021/ad.2019.31.2.121
- Navarro-Triviño FJ, Vega-Castillo JJ, Ruiz-Villaverde R. Nail changes successfully treated with dupilumab in a patient with severe atopic dermatitis. Australas J Dermatol. 2021;62:e468-e469. doi:10.1111/ajd.13633
- Wei SH, Huang YP, Liu MC, et al. An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010. BMC Infect Dis. 2011;11:346. doi:10.1186/1471-2334-11-346
- Shin JY, Cho BK, Park HJ. A clinical study of nail changes occurring secondary to hand-foot-mouth disease: onychomadesis and Beau’s lines. Ann Dermatol. 2014;26:280-283. doi:10.5021/ad.2014.26.2.280
- Verma S, Singal A. Nail changes in hand-foot-and-mouth disease (HFMD). Indian Dermatol Online J. 2021;12:656-657. doi:10.4103 /idoj.IDOJ_271_20
- Giordano LMC, de la Fuente LA, Lorca JMB, et al. Onychomadesis secondary to hand-foot-mouth disease: a frequent manifestation and cause of concern for parents. Article in Spanish. Rev Chil Pediatr. 2018;89:380-383. doi:10.4067/s0370-41062018005000203
- Justino MCA, da SMD, Souza MF, et al. Atypical hand-foot-mouth disease in Belém, Amazon region, northern Brazil, with detection of coxsackievirus A6. J Clin Virol. 2020;126:104307. doi:10.1016/j.jcv.2020.104307
- Cheng FF, Zhang BB, Cao ML, et al. Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis. Transl Pediatr. 2022;11:1502-1509. doi:10.21037/tp-22-352
- Nagata S. Causes of Kawasaki disease-from past to present. Front Pediatr. 2019;7:18. doi:10.3389/fped.2019.00018
- Mitsuishi T, Miyata K, Ando A, et al. Characteristic nail lesions in Kawasaki disease: case series and literature review. J Dermatol. 2022;49:232-238. doi:10.1111/1346-8138.16276
- Lindsley CB. Nail-bed lines in Kawasaki disease. Am J Dis Child. 1992;146:659-660. doi:10.1001/archpedi.1992.02160180017005
- Matsumura O, Nakagishi Y. Pincer nails upon convalescence from Kawasaki disease. J Pediatr. 2022;246:279. doi:10.1016/j.jpeds.2022.03.002
- Solís-Arias MP, García-Romero MT. Onychomycosis in children. a review. Int J Dermatol. 2017;56:123-130. doi:10.1111/ijd.13392
- Gupta AK, Mays RR, Versteeg SG, et al. Onychomycosis in children: safety and efficacy of antifungal agents. Pediatr Dermatol. 2018;35:552-559. doi:10.1111/pde.13561
- 49. Gupta AK, Venkataraman M, Shear NH, et al. Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis. Dermatol Ther. 2020;33:e13613. doi:10.1111/dth.13613
- Falotico JM, Lipner SR. Updated perspectives on the diagnosis and management of onychomycosis. Clin Cosmet Investig Dermatol. 2022;15:1933-1957. doi:10.2147/ccid.S362635
- Patel D, Castelo-Soccio LA, Rubin AI, et al. Laboratory monitoring during systemic terbinafine therapy for pediatric onychomycosis. JAMA Dermatol. 2017;153:1326-1327. doi:10.1001/jamadermatol.2017.4483
- Friedlander SF, Chan YC, Chan YH, et al. Onychomycosis does not always require systemic treatment for cure: a trial using topical therapy. Pediatr Dermatol. 2013;30:316-322. doi:10.1111/pde.12064
- Rich P, Spellman M, Purohit V, et al. Tavaborole 5% topical solution for the treatment of toenail onychomycosis in pediatric patients: results from a phase 4 open-label study. J Drugs Dermatol. 2019;18:190-195.
- Gupta AK, Venkataraman M, Abramovits W, et al. JUBLIA (efinaconazole 10% solution) in the treatment of pediatric onychomycosis. Skinmed. 2021;19:206-210.
- Gupta AK, Paquet M. Systemic antifungals to treat onychomycosis in children: a systematic review. Pediatr Dermatol. 2013;30:294-302. doi:10.1111/pde.12048
- Leggit JC. Acute and chronic paronychia. Am Fam Physician. 2017;96:44-51.
- Lipner SR, Scher RK. Congenital malalignment of the great toenails with acute paronychia. Pediatr Dermatol. 2016;33:e288-e289.doi:10.1111/pde.12924
Practice Points
- Nail plate pitting is the most common clinical sign of nail psoriasis in children.
- Nail changes are common in hand, foot, and mouth disease, with the most frequent being onychomadesis.
- Because onychomycosis may resemble other nail disorders, mycologic confirmation is recommended to avoid misdiagnosis.
- Many nail conditions in children self-resolve but recognizing these manifestations is important in providing anticipatory guidance to patients and caregivers.
Combination Therapy Looks Promising for Hepatitis D
, a multinational phase 2b open-label study in Europe found.
The combination resulted in higher rates of HDV RNA suppression levels at 24 weeks after end of treatment, especially at a higher, 10-mg dose of bulevirtide, according to researchers led by Tarik Asselah, MD. PhD, a professor of medicine and hepatology at Hôpital Beaujon, APHP, Clichy, France, and the University of Paris.
“This response appeared to be maintained from 24-48 weeks after the end of treatment — a finding that supports the concept that sustained undetectable HDV RNA for at least 1 year after treatment is possible in patients with chronic hepatitis D who have been treated with a finite duration of therapy of at least 96 weeks, including 48 weeks of peginterferon alfa-2a therapy,” the investigators wrote in The New England Journal of Medicine.
“As of today, there is no approved treatment for chronic HDV infection in the United States. Pegylated interferon alfa-2a, which is not approved for treatment of HDV, is the only option recommended by US treatment guidelines,” said study corresponding author Fabien Zoulim, MD, PhD, a hepatologist at the Lyon Hepatology Institute and a professor of medicine at the University of Lyon in France, in comments to GI & Hepatology News. “Bulevirtide 2 mg is approved for treating chronic HDV and compensated liver disease, and both bulevirtide and peginterferon are recommended options by the European treatment guidelines.”
The study found that most patients with undetectable HDV RNA levels during treatment-free follow-up showed no reduction in HepB surface antigen (HBsAg), suggesting an undetectable HDV RNA level can be achieved and sustained without HBsAg loss, the authors wrote.
While very small numbers in the combo groups and the higher-dose bulevirtide arm cleared HBsAg, “the study was not powered to evaluate the HBsAg response,” Dr. Zoulim said.
HDV is a defective virus that requires HBsAg for assembly and propagation, the authors noted. It affects as many as 20 million persons worldwide, and as the most severe form of chronic viral hepatitis, is associated with 2-6 times the risk of hepatocellular carcinoma and 2-3 times the risk of death associated with HBV monoinfection.
Though not common in the United States, it affects an estimated 10 to 20 million people worldwide (J Hepatol. 2020 Apr. doi: 10.1016/j.jhep.2020.04.008). One US database study found HepD in 4.6% of patients with HepB infection.
Commenting on the study but not a participant in it, Ahmet O. Gurakar, MD, AGAF, a professor of medicine in the sections of gastroenterology and hepatology at Johns Hopkins School of Medicine in Baltimore, Maryland, said the study findings look promising for the future treatment of HepD, but cautioned that it will be “a slow process to get approval for combination therapy with bulevirtide since the FDA has previously said it needs to see more studies. The findings need to be confirmed in larger groups, but it’s difficult to recruit enough patients in the United States for a trial since hepatitis D is not common in this country — it’s more common in the Mediterranean basin Eastern European populations.”
The Trial
The investigators randomly assigned 174, largely male, patients ages 18-65 (mean, about 41) years to receive one of four treatments:
- Pegylated interferon alfa-2a alone at 180 μg per week) for 48 weeks (n = 24).
- Bulevirtide at a daily dose of 2 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at 10 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at a daily dose of 10 mg alone for 96 weeks (n = 50).
All were followed for 48 weeks after treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group.
At 24 weeks post-treatment, HDV RNA was undetectable in 17% of patients in the peginterferon alfa-2a group. In the other arms, HDV RNA was undetectable in 32% in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of the 10-mg bulevirtide group.
For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15-50; P < .001).
At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% in the peginterferon alfa-2a group, 26% in the 2-mg bulevirtide plus peginterferon alfa-2a group, 46% in the 10-mg bulevirtide plus peginterferon alfa-2a group, and 12% in the 10-mg bulevirtide group.
Also calling the findings promising, Anna Lok, MBBS, MD, AGAF, a gastroenterologist at the University of Michigan, Ann Arbor, said that, “Given that the European Medicines Agency’s approval is for bulevirtide alone at 2 mg, results of this study should prompt reassessment whether bulevirtide should be used in combination with pegylated interferon in patients with no contraindications, and if 10 mg is more appropriate than a 2-mg dose.”
As to safety, the most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia, with the majority of adverse events being grade 1 or 2.
In comparison with other research, the current trial found that 70% in the 10-mg bulevirtide plus peginterferon alfa-2a group had an undetectable HDV RNA level at the end of treatment versus results of the Hep-Net International Delta Hepatitis Interventional Trial II (HIDIT-II), in which 33%-48% had undetectable levels after 96 weeks of peginterferon alfa-2a therapy, with or without tenofovir disoproxil. And in the phase 3 MYR301 trial, HDV RNA was undetectable in 20%-36% after 96 weeks of bulevirtide monotherapy.
The authors acknowledged that in addition to the lack of blinding, the trial was not designed to compare the two doses of bulevirtide and therefore lacked an adequate sample size to allow for formal comparisons. And although it included a peginterferon alfa-2a monotherapy group, it was not sufficiently powered to allow for comparison. They are currently considering plans for further studies in this area.
This study was funded by Gilead Sciences. Dr. Asselah disclosed consulting, safety/data monitoring, or travel for Gilead Sciences, AbbVie, Antio Therapeutics, Eiger Biopharmaceutical, Enyo Pharma, GlaxoSmithKline, Johnson & Johnson Healthcare Systems, and Vir Biotechnology. Dr. Zoulim reported consulting or research for multiple pharmaceutical/biotech companies, including Gilead Sciences. Numerous study coauthors declared financial relationships such as consulting, research, or employment with multiple private-sector companies, including Gilead Sciences. Dr. Lok and Dr. Gurakar disclosed no competing interests relevant to their comments.
, a multinational phase 2b open-label study in Europe found.
The combination resulted in higher rates of HDV RNA suppression levels at 24 weeks after end of treatment, especially at a higher, 10-mg dose of bulevirtide, according to researchers led by Tarik Asselah, MD. PhD, a professor of medicine and hepatology at Hôpital Beaujon, APHP, Clichy, France, and the University of Paris.
“This response appeared to be maintained from 24-48 weeks after the end of treatment — a finding that supports the concept that sustained undetectable HDV RNA for at least 1 year after treatment is possible in patients with chronic hepatitis D who have been treated with a finite duration of therapy of at least 96 weeks, including 48 weeks of peginterferon alfa-2a therapy,” the investigators wrote in The New England Journal of Medicine.
“As of today, there is no approved treatment for chronic HDV infection in the United States. Pegylated interferon alfa-2a, which is not approved for treatment of HDV, is the only option recommended by US treatment guidelines,” said study corresponding author Fabien Zoulim, MD, PhD, a hepatologist at the Lyon Hepatology Institute and a professor of medicine at the University of Lyon in France, in comments to GI & Hepatology News. “Bulevirtide 2 mg is approved for treating chronic HDV and compensated liver disease, and both bulevirtide and peginterferon are recommended options by the European treatment guidelines.”
The study found that most patients with undetectable HDV RNA levels during treatment-free follow-up showed no reduction in HepB surface antigen (HBsAg), suggesting an undetectable HDV RNA level can be achieved and sustained without HBsAg loss, the authors wrote.
While very small numbers in the combo groups and the higher-dose bulevirtide arm cleared HBsAg, “the study was not powered to evaluate the HBsAg response,” Dr. Zoulim said.
HDV is a defective virus that requires HBsAg for assembly and propagation, the authors noted. It affects as many as 20 million persons worldwide, and as the most severe form of chronic viral hepatitis, is associated with 2-6 times the risk of hepatocellular carcinoma and 2-3 times the risk of death associated with HBV monoinfection.
Though not common in the United States, it affects an estimated 10 to 20 million people worldwide (J Hepatol. 2020 Apr. doi: 10.1016/j.jhep.2020.04.008). One US database study found HepD in 4.6% of patients with HepB infection.
Commenting on the study but not a participant in it, Ahmet O. Gurakar, MD, AGAF, a professor of medicine in the sections of gastroenterology and hepatology at Johns Hopkins School of Medicine in Baltimore, Maryland, said the study findings look promising for the future treatment of HepD, but cautioned that it will be “a slow process to get approval for combination therapy with bulevirtide since the FDA has previously said it needs to see more studies. The findings need to be confirmed in larger groups, but it’s difficult to recruit enough patients in the United States for a trial since hepatitis D is not common in this country — it’s more common in the Mediterranean basin Eastern European populations.”
The Trial
The investigators randomly assigned 174, largely male, patients ages 18-65 (mean, about 41) years to receive one of four treatments:
- Pegylated interferon alfa-2a alone at 180 μg per week) for 48 weeks (n = 24).
- Bulevirtide at a daily dose of 2 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at 10 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at a daily dose of 10 mg alone for 96 weeks (n = 50).
All were followed for 48 weeks after treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group.
At 24 weeks post-treatment, HDV RNA was undetectable in 17% of patients in the peginterferon alfa-2a group. In the other arms, HDV RNA was undetectable in 32% in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of the 10-mg bulevirtide group.
For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15-50; P < .001).
At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% in the peginterferon alfa-2a group, 26% in the 2-mg bulevirtide plus peginterferon alfa-2a group, 46% in the 10-mg bulevirtide plus peginterferon alfa-2a group, and 12% in the 10-mg bulevirtide group.
Also calling the findings promising, Anna Lok, MBBS, MD, AGAF, a gastroenterologist at the University of Michigan, Ann Arbor, said that, “Given that the European Medicines Agency’s approval is for bulevirtide alone at 2 mg, results of this study should prompt reassessment whether bulevirtide should be used in combination with pegylated interferon in patients with no contraindications, and if 10 mg is more appropriate than a 2-mg dose.”
As to safety, the most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia, with the majority of adverse events being grade 1 or 2.
In comparison with other research, the current trial found that 70% in the 10-mg bulevirtide plus peginterferon alfa-2a group had an undetectable HDV RNA level at the end of treatment versus results of the Hep-Net International Delta Hepatitis Interventional Trial II (HIDIT-II), in which 33%-48% had undetectable levels after 96 weeks of peginterferon alfa-2a therapy, with or without tenofovir disoproxil. And in the phase 3 MYR301 trial, HDV RNA was undetectable in 20%-36% after 96 weeks of bulevirtide monotherapy.
The authors acknowledged that in addition to the lack of blinding, the trial was not designed to compare the two doses of bulevirtide and therefore lacked an adequate sample size to allow for formal comparisons. And although it included a peginterferon alfa-2a monotherapy group, it was not sufficiently powered to allow for comparison. They are currently considering plans for further studies in this area.
This study was funded by Gilead Sciences. Dr. Asselah disclosed consulting, safety/data monitoring, or travel for Gilead Sciences, AbbVie, Antio Therapeutics, Eiger Biopharmaceutical, Enyo Pharma, GlaxoSmithKline, Johnson & Johnson Healthcare Systems, and Vir Biotechnology. Dr. Zoulim reported consulting or research for multiple pharmaceutical/biotech companies, including Gilead Sciences. Numerous study coauthors declared financial relationships such as consulting, research, or employment with multiple private-sector companies, including Gilead Sciences. Dr. Lok and Dr. Gurakar disclosed no competing interests relevant to their comments.
, a multinational phase 2b open-label study in Europe found.
The combination resulted in higher rates of HDV RNA suppression levels at 24 weeks after end of treatment, especially at a higher, 10-mg dose of bulevirtide, according to researchers led by Tarik Asselah, MD. PhD, a professor of medicine and hepatology at Hôpital Beaujon, APHP, Clichy, France, and the University of Paris.
“This response appeared to be maintained from 24-48 weeks after the end of treatment — a finding that supports the concept that sustained undetectable HDV RNA for at least 1 year after treatment is possible in patients with chronic hepatitis D who have been treated with a finite duration of therapy of at least 96 weeks, including 48 weeks of peginterferon alfa-2a therapy,” the investigators wrote in The New England Journal of Medicine.
“As of today, there is no approved treatment for chronic HDV infection in the United States. Pegylated interferon alfa-2a, which is not approved for treatment of HDV, is the only option recommended by US treatment guidelines,” said study corresponding author Fabien Zoulim, MD, PhD, a hepatologist at the Lyon Hepatology Institute and a professor of medicine at the University of Lyon in France, in comments to GI & Hepatology News. “Bulevirtide 2 mg is approved for treating chronic HDV and compensated liver disease, and both bulevirtide and peginterferon are recommended options by the European treatment guidelines.”
The study found that most patients with undetectable HDV RNA levels during treatment-free follow-up showed no reduction in HepB surface antigen (HBsAg), suggesting an undetectable HDV RNA level can be achieved and sustained without HBsAg loss, the authors wrote.
While very small numbers in the combo groups and the higher-dose bulevirtide arm cleared HBsAg, “the study was not powered to evaluate the HBsAg response,” Dr. Zoulim said.
HDV is a defective virus that requires HBsAg for assembly and propagation, the authors noted. It affects as many as 20 million persons worldwide, and as the most severe form of chronic viral hepatitis, is associated with 2-6 times the risk of hepatocellular carcinoma and 2-3 times the risk of death associated with HBV monoinfection.
Though not common in the United States, it affects an estimated 10 to 20 million people worldwide (J Hepatol. 2020 Apr. doi: 10.1016/j.jhep.2020.04.008). One US database study found HepD in 4.6% of patients with HepB infection.
Commenting on the study but not a participant in it, Ahmet O. Gurakar, MD, AGAF, a professor of medicine in the sections of gastroenterology and hepatology at Johns Hopkins School of Medicine in Baltimore, Maryland, said the study findings look promising for the future treatment of HepD, but cautioned that it will be “a slow process to get approval for combination therapy with bulevirtide since the FDA has previously said it needs to see more studies. The findings need to be confirmed in larger groups, but it’s difficult to recruit enough patients in the United States for a trial since hepatitis D is not common in this country — it’s more common in the Mediterranean basin Eastern European populations.”
The Trial
The investigators randomly assigned 174, largely male, patients ages 18-65 (mean, about 41) years to receive one of four treatments:
- Pegylated interferon alfa-2a alone at 180 μg per week) for 48 weeks (n = 24).
- Bulevirtide at a daily dose of 2 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at 10 mg plus peginterferon alfa-2a at 180 μg per week for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks (n = 50).
- Bulevirtide at a daily dose of 10 mg alone for 96 weeks (n = 50).
All were followed for 48 weeks after treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group.
At 24 weeks post-treatment, HDV RNA was undetectable in 17% of patients in the peginterferon alfa-2a group. In the other arms, HDV RNA was undetectable in 32% in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of the 10-mg bulevirtide group.
For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15-50; P < .001).
At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% in the peginterferon alfa-2a group, 26% in the 2-mg bulevirtide plus peginterferon alfa-2a group, 46% in the 10-mg bulevirtide plus peginterferon alfa-2a group, and 12% in the 10-mg bulevirtide group.
Also calling the findings promising, Anna Lok, MBBS, MD, AGAF, a gastroenterologist at the University of Michigan, Ann Arbor, said that, “Given that the European Medicines Agency’s approval is for bulevirtide alone at 2 mg, results of this study should prompt reassessment whether bulevirtide should be used in combination with pegylated interferon in patients with no contraindications, and if 10 mg is more appropriate than a 2-mg dose.”
As to safety, the most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia, with the majority of adverse events being grade 1 or 2.
In comparison with other research, the current trial found that 70% in the 10-mg bulevirtide plus peginterferon alfa-2a group had an undetectable HDV RNA level at the end of treatment versus results of the Hep-Net International Delta Hepatitis Interventional Trial II (HIDIT-II), in which 33%-48% had undetectable levels after 96 weeks of peginterferon alfa-2a therapy, with or without tenofovir disoproxil. And in the phase 3 MYR301 trial, HDV RNA was undetectable in 20%-36% after 96 weeks of bulevirtide monotherapy.
The authors acknowledged that in addition to the lack of blinding, the trial was not designed to compare the two doses of bulevirtide and therefore lacked an adequate sample size to allow for formal comparisons. And although it included a peginterferon alfa-2a monotherapy group, it was not sufficiently powered to allow for comparison. They are currently considering plans for further studies in this area.
This study was funded by Gilead Sciences. Dr. Asselah disclosed consulting, safety/data monitoring, or travel for Gilead Sciences, AbbVie, Antio Therapeutics, Eiger Biopharmaceutical, Enyo Pharma, GlaxoSmithKline, Johnson & Johnson Healthcare Systems, and Vir Biotechnology. Dr. Zoulim reported consulting or research for multiple pharmaceutical/biotech companies, including Gilead Sciences. Numerous study coauthors declared financial relationships such as consulting, research, or employment with multiple private-sector companies, including Gilead Sciences. Dr. Lok and Dr. Gurakar disclosed no competing interests relevant to their comments.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Genetics and Lifestyle Choices Can Affect Early Prostate Cancer Deaths
TOPLINE:
METHODOLOGY:
- About one third of men die from prostate cancer before age 75, highlighting the need for prevention strategies that target high-risk populations.
- In the current study, researchers analyzed data from two prospective cohort studies — the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS) — which included 19,607 men with a median age at inclusion of 59 years (MDCS) and 65.1 years (HPFS) followed from 1991 to 2019.
- Participants were categorized by genetic risk and lifestyle score. Genetic risk was defined using a multiancestry polygenic risk score (PRS) for overall prostate cancer that included 400 genetic risk variants.
- A healthy lifestyle score was defined as 3-6, while an unhealthy lifestyle score was 0-2. Lifestyle factors included smoking, weight, physical activity, and diet.
- The researchers calculated hazard ratios (HRs) for the association between genetic and lifestyle factors and prostate cancer death.
TAKEAWAY:
- Combining the PRS and family history of cancer, 67% of men overall (13,186 of 19,607) were considered to have higher genetic risk, and about 30% overall had an unhealthy lifestyle score of 0-2.
- Men at higher genetic risk accounted for 88% (94 of 107) of early prostate cancer deaths.
- Compared with men at lower genetic risk, those at higher genetic risk had more than a threefold higher rate of early prostate cancer death (HR, 3.26) and more than a twofold increased rate of late prostate cancer death (HR, 2.26) as well as a higher lifetime risk for prostate cancer death.
- Among men at higher genetic risk, an unhealthy lifestyle was associated with a higher risk of early prostate cancer death, with smoking and a BMI of ≥ 30 being significant factors. Depending on the definition of a healthy lifestyle, the researchers estimated that 22%-36% of early prostate cancer deaths among men at higher genetic risk might be preventable.
IN PRACTICE:
“Based on data from two prospective cohort studies, this analysis provides evidence for targeting men at increased genetic risk with prevention strategies aimed at reducing premature deaths from prostate cancer,” the researchers concluded.
SOURCE:
The study, with first author Anna Plym, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet in Stockholm, Sweden, was published online on July 3 in JAMA Network Open.
LIMITATIONS:
Differences in prostate cancer testing and treatment may account for some of the observed association between a healthy lifestyle and prostate cancer death. This analysis provides an estimate of what is achievable in terms of prevention had everyone adopted a healthy lifestyle. The authors only considered factors at study entry, which would not include changes that happen later.
DISCLOSURES:
The study authors reported several disclosures. Fredrik Wiklund, PhD, received grants from GE Healthcare, personal fees from Janssen, Varian Medical Systems, and WebMD, and stock options and personal fees from Cortechs Labs outside the submitted work. Adam S. Kibel, MD, received personal fees from Janssen, Pfizer, Bristol Myers Squibb, Cellvax, Merck, and Roche and served as a consultant for Bristol Myers Squibb and Candel outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- About one third of men die from prostate cancer before age 75, highlighting the need for prevention strategies that target high-risk populations.
- In the current study, researchers analyzed data from two prospective cohort studies — the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS) — which included 19,607 men with a median age at inclusion of 59 years (MDCS) and 65.1 years (HPFS) followed from 1991 to 2019.
- Participants were categorized by genetic risk and lifestyle score. Genetic risk was defined using a multiancestry polygenic risk score (PRS) for overall prostate cancer that included 400 genetic risk variants.
- A healthy lifestyle score was defined as 3-6, while an unhealthy lifestyle score was 0-2. Lifestyle factors included smoking, weight, physical activity, and diet.
- The researchers calculated hazard ratios (HRs) for the association between genetic and lifestyle factors and prostate cancer death.
TAKEAWAY:
- Combining the PRS and family history of cancer, 67% of men overall (13,186 of 19,607) were considered to have higher genetic risk, and about 30% overall had an unhealthy lifestyle score of 0-2.
- Men at higher genetic risk accounted for 88% (94 of 107) of early prostate cancer deaths.
- Compared with men at lower genetic risk, those at higher genetic risk had more than a threefold higher rate of early prostate cancer death (HR, 3.26) and more than a twofold increased rate of late prostate cancer death (HR, 2.26) as well as a higher lifetime risk for prostate cancer death.
- Among men at higher genetic risk, an unhealthy lifestyle was associated with a higher risk of early prostate cancer death, with smoking and a BMI of ≥ 30 being significant factors. Depending on the definition of a healthy lifestyle, the researchers estimated that 22%-36% of early prostate cancer deaths among men at higher genetic risk might be preventable.
IN PRACTICE:
“Based on data from two prospective cohort studies, this analysis provides evidence for targeting men at increased genetic risk with prevention strategies aimed at reducing premature deaths from prostate cancer,” the researchers concluded.
SOURCE:
The study, with first author Anna Plym, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet in Stockholm, Sweden, was published online on July 3 in JAMA Network Open.
LIMITATIONS:
Differences in prostate cancer testing and treatment may account for some of the observed association between a healthy lifestyle and prostate cancer death. This analysis provides an estimate of what is achievable in terms of prevention had everyone adopted a healthy lifestyle. The authors only considered factors at study entry, which would not include changes that happen later.
DISCLOSURES:
The study authors reported several disclosures. Fredrik Wiklund, PhD, received grants from GE Healthcare, personal fees from Janssen, Varian Medical Systems, and WebMD, and stock options and personal fees from Cortechs Labs outside the submitted work. Adam S. Kibel, MD, received personal fees from Janssen, Pfizer, Bristol Myers Squibb, Cellvax, Merck, and Roche and served as a consultant for Bristol Myers Squibb and Candel outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- About one third of men die from prostate cancer before age 75, highlighting the need for prevention strategies that target high-risk populations.
- In the current study, researchers analyzed data from two prospective cohort studies — the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS) — which included 19,607 men with a median age at inclusion of 59 years (MDCS) and 65.1 years (HPFS) followed from 1991 to 2019.
- Participants were categorized by genetic risk and lifestyle score. Genetic risk was defined using a multiancestry polygenic risk score (PRS) for overall prostate cancer that included 400 genetic risk variants.
- A healthy lifestyle score was defined as 3-6, while an unhealthy lifestyle score was 0-2. Lifestyle factors included smoking, weight, physical activity, and diet.
- The researchers calculated hazard ratios (HRs) for the association between genetic and lifestyle factors and prostate cancer death.
TAKEAWAY:
- Combining the PRS and family history of cancer, 67% of men overall (13,186 of 19,607) were considered to have higher genetic risk, and about 30% overall had an unhealthy lifestyle score of 0-2.
- Men at higher genetic risk accounted for 88% (94 of 107) of early prostate cancer deaths.
- Compared with men at lower genetic risk, those at higher genetic risk had more than a threefold higher rate of early prostate cancer death (HR, 3.26) and more than a twofold increased rate of late prostate cancer death (HR, 2.26) as well as a higher lifetime risk for prostate cancer death.
- Among men at higher genetic risk, an unhealthy lifestyle was associated with a higher risk of early prostate cancer death, with smoking and a BMI of ≥ 30 being significant factors. Depending on the definition of a healthy lifestyle, the researchers estimated that 22%-36% of early prostate cancer deaths among men at higher genetic risk might be preventable.
IN PRACTICE:
“Based on data from two prospective cohort studies, this analysis provides evidence for targeting men at increased genetic risk with prevention strategies aimed at reducing premature deaths from prostate cancer,” the researchers concluded.
SOURCE:
The study, with first author Anna Plym, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet in Stockholm, Sweden, was published online on July 3 in JAMA Network Open.
LIMITATIONS:
Differences in prostate cancer testing and treatment may account for some of the observed association between a healthy lifestyle and prostate cancer death. This analysis provides an estimate of what is achievable in terms of prevention had everyone adopted a healthy lifestyle. The authors only considered factors at study entry, which would not include changes that happen later.
DISCLOSURES:
The study authors reported several disclosures. Fredrik Wiklund, PhD, received grants from GE Healthcare, personal fees from Janssen, Varian Medical Systems, and WebMD, and stock options and personal fees from Cortechs Labs outside the submitted work. Adam S. Kibel, MD, received personal fees from Janssen, Pfizer, Bristol Myers Squibb, Cellvax, Merck, and Roche and served as a consultant for Bristol Myers Squibb and Candel outside the submitted work. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Good Vibrations: Help Patients Help Themselves to Better Sex
This transcript has been edited for clarity.
Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?
Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.
Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?
Dr. Herbenick: The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.
Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”
Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.
Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.
Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.
Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.
Dr. Herbenick: Absolutely.
Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?
Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.
Dr. Rubin: Thank you so much for joining us today.
Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?
Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.
Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?
Dr. Herbenick: The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.
Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”
Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.
Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.
Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.
Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.
Dr. Herbenick: Absolutely.
Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?
Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.
Dr. Rubin: Thank you so much for joining us today.
Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?
Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.
Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?
Dr. Herbenick: The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.
Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”
Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.
Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.
Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.
Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.
Dr. Herbenick: Absolutely.
Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?
Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.
Dr. Rubin: Thank you so much for joining us today.
Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.
A version of this article first appeared on Medscape.com.
ASCO 2024: An Expert’s Top Hematology Highlights
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.
In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.
Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?
Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.
The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.
Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?
Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.
Q: What’s new about this kind of research?
Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.
Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?
Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.
In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.
This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.
Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?
Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.
[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]
Q: What makes this drug unique?
Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.
Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?
Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.
This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.
Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?
Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.
Dr. Kamal has no disclosures to report.
Key Questions to Ask Patients With Somatic Symptom Disorder
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.
How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
One Common Factor
Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.
In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.
According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.
In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”
“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”
This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
The ‘Prediction Machine’
Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.
Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.
These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.
“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.
The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
What Can Doctors Do?
Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:
- Consider the subjective experience. “The psychologic aspect is relevant in every illness. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
- Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
- Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.
A Doctor’s ‘Toolbox’
A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.
In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.
The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.
Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.
In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).
After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).
“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
Guideline Under Revision
Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.
Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.
“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”
Dr. Henningsen declared no conflicts of interest.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.