MDedge Dermatology

Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

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Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

--

Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

Alopecia areata (AA) is an autoimmune disease that affects 2% of the population. Janus kinase (JAK) signaling has been shown to improve outcomes for many patients with severe AA, as outlined by Dr Brittany Craiglow, associate professor adjunct, Yale School of Medicine, New Haven, Connecticut.

Dr Craiglow reports that in AA, hair loss can be caused by key cytokines, including interleukin 15 and interferon gamma. These cytokines use the JAK-STAT pathway to transmit their signal. JAK inhibitors, which interfere with that pathway, are showing to be an effective treatment that can lead to hair growth.

Two JAK inhibitors have received US Food and Drug Administration approval for treatment of severe AA. Oral JAK1/2 inhibitor baricitinib has been approved for patients aged 18 years or older. The oral JAK3 inhibitor ritlecitinib has been approved for patients aged 12 years or older.

Dr Craiglow looks at clinical trials involving these JAK inhibitors. The results show that patients are more likely to respond to treatment earlier in the disease process. The study also found that patients with less severe hair loss (50%-94%) respond better than did those with severe hair loss.

Finally, Dr Craiglow explores the topic of JAK inhibitor selection. She notes that different medications will hit different JAK proteins, the failure of one JAK inhibitor does not always predict failure of another. Dr Craiglow points to current efficacy of these targeted therapies and expresses optimism about the future of personalized medicine in treating patients with severe AA.

--

Brittany Craiglow, MD, Associate Professor Adjunct, Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut

Brittany Craiglow, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for:

AbbVie; BiologicsMD; Dermavant; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme; Sun Pharmaceuticals

Serve(d) as a speaker or a member of a speaker’s bureau for: AbbVie; Incyte; Eli Lilly; Pfizer; Regeneron; Sanofi-Genzyme

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

It’s time to renew two of my three narcotic prescribing licenses. For the first time in my career, I’ve waffled on whether the financial outlay to the US Drug Enforcement Agency (DEA) is worth it. 

At $888 each, I’ve considered letting two licenses lapse because I only work part-time in Montana. But several friends advised me to keep a “spare” in case I transfer to a new location. 

I thought about just paying the fees until I could do a little more research, but there is no mechanism for a refund unless I die within the first year of the 3-year cycle, provide incorrect credit card digits, or accidentally duplicate payments.

The renewal fee is just part of the issue.
 

Mandatory 8-Hour Training

I also received an alert about the requirement for more “narcotics prescribing education” thanks to the Medication Access and Training Expansion Act (MATE). 

The requirement seems counterintuitive because opioid prescribing has decreased for the 10th consecutive year, according to the AMA Overdose Epidemic Report. The continuing rise in overdose deaths is largely due to illegitimate manufacturing of synthetic opioids. 

I’ve written zero outpatient narcotics prescriptions in the past 6 years, and I’ve written very few in my 33 years of practice. My use is limited to intravenous morphine for flash pulmonary edema or refractory angina, but unless you graduated from a training program within 5 years of the June 2023 mandate or are boarded in addiction medicine, there is no way to escape the 8-hour education requirement.

The problem is that these courses are never just 8 hours in duration. After signing up for one such CME course that cost $150, I was still dying of boredom and at risk for DVT 4 days later. That’s how long it took to sit through.

Instead of the 30 seconds it should have taken to review the simple instructions to deliver Narcan, there were scores of screens followed by juvenile quizlets and cartoons. All but about 2 hours out of the 4 days is now relegated to that category of “hours of my life that I can never get back.” Additionally, none of that mandatory “education” will change my prescribing habits one whit. 

And beware the penalty. 

Changes Needed

The only good thing that came of those 4 long days of opioid education was a motivation to drive change in our current licensing and educational experience. Why not use this opportunity to reform the DEA-physician/prescriber relationship? 

The educational requirements should be curtailed for those of us who do not provide outpatient narcotic prescriptions even if we use inpatient opioids. Meds with low abuse potential should be rescheduled to minimize who gets caught in the broad net of the education requirement. 

We should reduce overregulation of the legitimate prescribers by lowering, instead of increasing, licensing fees. We should change to a single license number that covers every state. In this digital age, there is no legitimate excuse to prevent this from happening. 

After all, the settlements from opioid manufacturers and distributors will in time total $50 billion. It seems that at least some of the responsibilities of the DEA could shift to states, cities, and towns. 

My friend Siamak Karimian, MD, who provides locum services in multiple states, pays for seven active DEA licenses every 3 years. He pointed out the hypocrisy in the current regulatory system: “It’s funny that you can have only one DEA or state license and work for the government in all other states or territories with no limits, including the VA, Indian healthcare systems, or prison systems.”

All other prescribers require a separate DEA number for every state. Ultimately, you’d think tracking prescriptions for a single DEA number should be far simpler than tracking someone with seven. 

Competent physicians not guilty of criminal overprescribing seem to be the last to be considered in nearly every healthcare endeavor these days. It would be refreshing if they would reduce our fees and prevent this waste of our time. 

And while we are at it, perhaps a more fitting punishment is due for Richard Sackler and all the Purdue Pharma–affiliated family members. The Sacklers will pay out $6 billion in exchange for immunity against civil litigation. That doesn’t seem like much when they are worth $11 billion. 

Perhaps they should be made to take an 8-hour course on opioid prescribing, annually and in perpetuity. Let’s see them complete a few quizlets and sit through screens of instruction on how to administer Naloxone. Of course, that would be a mild punishment for those who manufactured a drug that killed hundreds of thousands. But it would be a start. 
 

Dr. Walton-Shirley, a clinical cardiologist in Nashville, Tennessee, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

Despite an expanding arsenal of disease-modifying antirheumatic drugs (DMARDs), many patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) still struggle to reach remission even after trying multiple advanced treatments.

Now, international groups of experts are working to better define these “difficult-to-treat” patients to both inform care and improve selection of participants for future clinical trials.

“The idea is rather simple, and the need is relatively ubiquitous,” Denis Poddubnyy, MD, of the Charité – Universitätsmedizin Berlin and the German Rheumatism Research Center Berlin, both in Berlin, Germany, said in an interview. He is the co-primary investigator for the ongoing Assessment of SpondyloArthritis International Society (ASAS) project to develop a consensus definition of difficult-to-treat axSpA.

According to ASAS, only 40%-50% of patients with axSpA achieve a 40% improvement in ASAS response criteria (ASAS40), and few (10%-20%) achieve remission in the first 4-6 months of treatment.

Multiple Reasons for Nonresponse

“While the term difficult-to-treat can refer to refractory disease, that is not the only reason why a patient might not be responding to medication. In fact, it’s likely that truly biologically refractory disease makes up only a fraction of cases that respond inadequately to treatment,” said Shikha Singla, MD, who directs the psoriatic arthritis program at the Medical College of Wisconsin in Milwaukee. She is also involved with the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiative to define Difficult-to-Treat and Complex-to-Manage PsA.

Medical College of Wisconsin

“Apart from the persistent articular and periarticular inflammation, there could be multiple noninflammatory factors that may be contributing to this treatment-resistant disease, including comorbid conditions such as obesity, cardiovascular disease, fibromyalgia, and even social factors such as limited access to medications,” she told this news organization. “Given these complexities, it is a matter of supreme importance to recognize and carefully delineate the elements that contribute to treatment refractory disease: Is it truly the inflammation, or are there noninflammatory components that are causing the treatment failure, or a combination of the two?”

Other contributing factors could be depression, hypersensitization, and comorbidities that prevent certain treatment approaches, added Fabian Proft, MD, also of Charité – Universitätsmedizin Berlin. Dr. Proft discussed these difficult-to-treat definition efforts at the recent Spondyloarthritis Research and Treatment Network (SPARTAN) annual meeting held in Cleveland. Patients also might not be taking their medication regularly and may be seeking alternative medicine approaches, he said.

Dr. Proft

The Definitions

Terminology for these two groups can vary by professional society. The European Alliance of Associations for Rheumatology (EULAR) published a definition for “difficult-to-treat” rheumatoid arthritis (RA) that includes cases with “both inflammatory activity and/or noninflammatory complaints.”

The definition includes three criteria:

1) Treatment according to EULAR recommendation and failure of at least two biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated)

2) Signs suggestive of active/progressive disease, including at least one of the following:

• Moderate disease activity (according to validated composite measures including joint counts)
• Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease, whether joint-related or other
• Inability to taper glucocorticoid treatment
• Rapid radiographic progression (with or without signs of active disease)
• RA symptoms that are causing a reduction in quality of life

3) Symptom/sign management perceived as problematic by the rheumatologist or the patient

All three criteria must be met.

Both GRAPPA and ASAS plan to use the term “difficult-to-treat” or “treatment refractory” to describe true biologically refractory inflammatory disease and are categorizing the larger, heterogeneous group of nonresponders as “difficult-to-manage” (ASAS) or “complex-to-manage” (GRAPPA).

According to Dr. Poddubnyy, the agreed ASAS definition of difficult-to-manage has several similarities with EULAR’s RA definition, including three pillars:

• Treatment according to existing recommendations and failure of at least two different bDMARDs or tsDMARDs with different mechanisms
• Having signs and symptoms of disease (measured by high disease activity by certain disease activity indexes, persistently elevated C-reactive protein, inflammation on MRI, or rapid radiographic spinal progression)
• Symptoms/signs of disease that are considered problematic by the provider or patient

The definition was approved in January, and the manuscript is in the works, Dr. Poddubnyy said.

The GRAPPA project on PsA is still in its early stages, which so far has included a comprehensive literature review as well as a survey of GRAPPA members across 47 countries. The group is generally in agreement that two separate definitions for nonresponse to treatment are necessary, and that the “difficult-to-treat” definition — which identifies true refractory disease — should include objective signs of inflammation, Dr. Singla said.
 

Looking Forward

The next step of the ASAS project is to “define the pathway” from difficult-to-manage axSpA to treatment refractory disease, Dr. Poddubnyy said.

“What should be ruled out in order to exclude so-called noninflammatory causes of pain?” he continued. “It will require some Delphi exercises and [a] consensus approach.”

Proft anticipates that this treatment refractory definition in both axSpA and PsA will be most useful in research, rather than clinical practice.

“It is really important to have unified definition criteria to shape as homogeneous a cohort as possible,” he said, for future clinical trials in this population.

On the other hand, the complex/difficult-to-manage definition may be more useful for clinical practice, Dr. Proft thought.

“If you see a patient not responding to treatment, the easiest thing you can do would be to change treatment,” like swapping one biologic for another, Dr. Poddubnyy added, “but this would not be the right approach in every patient.” One goal of these initiatives is to give guidance on “what things should be looked after or excluded before you conclude this is biological [nonresponse],” he said.

Dr. Singla consults for AbbVie, Janssen, and UCB and received research funding from Eli Lilly. Dr. Poddubnyy disclosed serving as a speaker, consultant, and/or research grant recipient for multiple companies including AbbVie, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, GlaxoSmithKline, Novartis, and UCB. Dr. Proft reported receiving research grants, consultant fees, or support for attending meetings and/or travel from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Medscape Medical News, Galapagos, and Hexal. Dr. Proft also participants on a data safety monitoring board or advisory board for AbbVie, Celgene, Janssen, Novartis, and UCB.

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

VIENNA — Anti-Ro/SSA antibodies may help predict which patients with systemic sclerosis (SSc) are at a greater risk for interstitial lung disease (ILD) and may serve as a biomarker to guide screening, according to an analysis of data from a large European cohort.

The researchers were led by Blaž Burja, MD, PhD, a physician-scientist at the Center of Experimental Rheumatology, University Hospital Zürich, Switzerland, who reported that anti-Ro/SSA antibodies are a risk factor for ILD, with an odds ratio of 1.24, in patients with SSc.

At the annual European Congress of Rheumatology, he presented the findings of the study that aimed to find out if SSc-nonspecific antibodies might help better risk-stratify patients with SSc, focusing on lung involvement. “Among them, anti-Ro/SSA antibodies have been shown to be associated with interstitial lung disease in different connective tissue diseases,” Dr. Burja pointed out.

“A total of 15% of all patients in the SSc cohort presented with anti-Ro/SSA antibodies, and this subgroup presented with distinct clinical features: Importantly, higher prevalence of ILD and lower DLCO% [diffusing capacity of the lungs for carbon monoxide] in patients with established ILD,” reported Dr. Burja. “However, these anti-Ro/SSA antibodies do not predict ILD progression, death, or overall disease progression.”

Based on the findings, Dr. Burja suggested that these antibodies be incorporated into routine clinical practice to identify patients with SSc who have a high risk for ILD. He noted that “this has specific importance in clinical settings without availability of high-resolution computed tomography (HRCT), where anti-Ro/SSA antibodies could represent an additional biomarker to guide the screening process, in particular, in patients without SSc-specific antibodies.”

Caroline Ospelt, MD, PhD, co-moderator of the session and scientific program chair of EULAR 2024, told this news organization that the study was unique in its approach to studying ILD risk by “looking outside the box, so not just at specific antibodies but whether cross-disease antibodies may have value in stratifying patients and help predict risk of lung involvement and possibly monitor these patients.”

Dr. Ospelt, professor of experimental rheumatology at University Hospital Zürich, who was not involved in the study, noted: “It might also be the case that we could adapt this concept and use these antibodies in other rheumatic diseases, too, not just systemic sclerosis, to predict lung involvement.”
 

Risk-Stratifying With SSc-Nonspecific Antibodies

Dr. Burja explained that despite better stratification of patients with SSc with SSc-specific antibodies, “in clinical practice, we see large heterogeneity, and individual prognosis with regards to outcomes is still unpredictable, so we wanted to know whether by using nonspecific autoantibodies we might be better able to risk-stratify these patients.”

A study population of 4421 with at least one follow-up visit, including 3060 patients with available follow-up serologic data, was drawn from the European Scleroderma Trials and Research group database (n = 22,482). Of these 3060 patients, 461 were positive for anti-Ro/SSA antibodies and 2599 were negative. The researchers analyzed the relationships between baseline characteristics and the development or progression of ILD over 2.7 years of follow-up. Incident, de novo ILD was defined based on its presence on HRCT, and progression was defined by whether the percentage of predicted forced vital capacity (FVC%) dropped ≥ 10%, FVC% dropped 5%-9% in association with a DLCO% drop ≥ 15%, or FVC% dropped > 5%. Deaths from all causes and prognostic factors for the progression of lung fibrosis during follow-up were recorded.
 

High Prevalence of ILD With Anti-Ro/SSA Antibodies in SSc

At baseline, patients with anti-Ro/SSA antibodies were aged 55-56 years, 84%-87% were women, and muscular involvement was present in 18% of patients positive for anti-Ro/SSA antibodies and 12.5% of those who were negative (P < .001). According to HRCT, ILD was present in 56.2% of patients positive for anti-Ro/SSA antibodies and in 47.8% of those who were negative (P = .001). FVC% was 92.5% in patients positive for anti-Ro/SSA antibodies and 95.7% in those who were negative (P = .002). DLCO% was 66.9% in patients positive for anti-Ro/SSA antibodies and 71% in those who were negative (P < .001).

“A total of 15% of all SSc patients presented as positive for anti-Ro/SSA antibodies, and these patients all presented with higher prevalence of SSA-nonspecific antibodies, too: Of note, those with anti-La/SSB and anti-U1/RNP and rheumatoid factor,” Dr. Burja reported.

In patients with anti-U1/RNP autoantibodies, 1% were positive and 4% were negative for anti-Ro/SSA antibodies; in those with anti-La/SSB autoantibodies, 17% were positive and 1% were negative for anti-Ro/SSA antibodies; and in those with rheumatoid factor, 28% were positive and 14% were negative for anti-Ro/SSA antibodies.

Dr. Burja pointed out that the average disease duration in the study cohort at baseline was 7 years, “and at this timepoint, we expect to see some common disease manifestations. Specifically, higher muscular involvement and higher ILD based on HRCT.

“We decided to focus on patients with established ILD at baseline,” said Dr. Burja. “Anti-Ro/SSA-positive patients with established ILD at baseline presented with lower DLCO values at 59% in patients positive for anti-Ro/SSA antibodies and 61% for those who were negative.”

After conducting a multivariable analysis of 14,066 healthcare visits and adjusting for known risk factors for ILD, the researchers concluded that anti-Ro/SSA antibodies are an independent risk factor for ILD, with an odds ratio of 1.24 (95% CI, 1.07-1.44; P = .006). They also determined that anti-Ro/SSA antibodies are a risk factor for lower DLCO values in patients with ILD, with a regression coefficient of −1.93.

The researchers then explored the progression of ILD and overall disease progression and survival during the follow-up period in a longitudinal analysis. “However, anti-Ro/SSA antibodies were not found to predict the progression of ILD,” reported Dr. Burja, adding that this was true regardless of the definition of ILD progression used. “Nor did anti-Ro/SSA antibodies do not predict survival or overall disease progression.”

Dr. Burja pointed out the limitations in his study, including the lack of standardized criteria for all centers to assess anti-Ro/SSA positivity; there was a lack of discrimination between anti-Ro52 and anti-Ro60 subtypes, and there were no standardized applicable criteria to study lung progression in SSc.

Dr. Burja and Dr. Ospelt had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The Diagnosis: Erythema Ab Igne

Based on the patient's long-standing history of back pain treated with heating pads as well as the normal laboratory findings and skin examination, a diagnosis of erythema ab igne (EAI) was made.

Erythema ab igne presents as reticulated brownish erythema or hyperpigmentation on sites exposed to prolonged use of heat sources such as heating pads, laptops, and space heaters. Erythema ab igne most commonly affects the lower back, thighs, or legs^1-6; however, EAI can appear on atypical sites such as the forehead and eyebrows due to newer technology (eg, virtual reality headsets).⁷ The level of heat required for EAI to occur is below the threshold for thermal burns (<45 °C [113 °F]).1 Erythema ab igne can occur at any age, and woman are more commonly affected than men.⁸ The pathophysiology currently is unknown; however, recurrent and prolonged heat exposure may damage superficial vessels. As a result, hemosiderin accumulates in the skin, and hyperpigmentation subsequently occurs.⁹

The diagnosis of EAI is clinical, and early stages of the rash present as blanching reticulated erythema in areas associated with heat exposure. If the offending source of heat is not removed, EAI can progress to nonblanching, fixed, hyperpigmented plaques with skin atrophy, bullae, or hyperkeratosis. Patients often are asymptomatic; however, mild burning may occur.² Histopathology reveals cellular atypia, epidermal atrophy, dilation of dermal blood vessels, a minute inflammatory infiltrate, and keratinocyte apoptosis.¹⁰ Skin biopsy may be necessary in cases of suspected malignancy due to chronic heat exposure. Lesions that ulcerate or evolve should raise suspicion for malignancy.¹¹ Squamous cell carcinoma is the most common malignancy associated with EAI; other malignancies that may manifest include basal cell carcinoma, Merkel cell carcinoma, or cutaneous marginal zone lymphoma.^2,12-14

Erythema ab igne often is mistaken for livedo reticularis, which appears more erythematous without hyperpigmentation or epidermal changes and may be associated with a pathologic state.¹⁵ The differential diagnosis in our patient, who was in her 40s with a history of fatigue and joint pain, included livedo reticularis associated with lupus; however, the history of heating pad use, normal laboratory findings, and presence of epidermal changes suggested EAI. Lupus typically affects the hand and knee joints.¹⁶ Additionally, livedo reticularis more commonly appears on the legs.¹⁵

Other differentials for EAI include livedo racemosa, cutaneous T-cell lymphoma, and cutis marmorata. Livedo racemosa presents with broken rings of erythema in young to middle-aged women and primarily affects the trunk and proximal limbs. It is associated with an underlying condition such as polyarteritis nodosa and less commonly with lupus erythematosus with antiphospholipid or Sneddon syndrome.^15,17 Cutaneous T-cell lymphoma typically manifests with poikilodermatous patches larger than the palm, especially in covered areas of skin.¹⁸ Cutis marmorata is transient and temperature dependent.⁹

The key intervention for EAI is removal of the offending heat source.² Patients should be counseled that the erythema and hyperpigmentation may take months to years to resolve. Topical hydroquinone or tretinoin may be used in cases of persistent hyperpigmentation.¹⁹ Patients who continue to use heating pads for long-standing pain should be advised to limit their use to short intervals without occlusion. If malignancy is a concern, a biopsy should be performed.²⁰

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has granted accelerated approval to repotrectinib (Augtyro, Bristol Myers Squibb) for all locally advanced, unresectable, or metastatic solid tumors with an NTRK gene fusion that have progressed after initial treatment or that have no satisfactory alternative therapies.

The approval is a label expansion for the tyrosine kinase inhibitor (TKI), which received initial clearance in November 2023 for locally advanced or metastatic ROS1-positive non–small cell lung cancer. 

NTRK gene fusions are genetic abnormalities wherein part of the NTRK gene fuses with an unrelated gene. The abnormal gene can then produce an oncogenic protein. Although rare, these mutations are found in many cancer types.

The approval, for adult and pediatric patients aged 12 years or older, was based on the single-arm open-label TRIDENT-1 trial in 88 adults with locally advanced or metastatic NTRK gene fusion solid tumors.

In the 40 patients who were TKI-naive, the overall response rate was 58%, and the median duration of response was not estimable. In the 48 patients who had a TKI previously, the overall response rate was 50% and median duration of response was 9.9 months.

In 20% or more of participants, treatment caused dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Labeling warns of central nervous system reactions, interstitial lung disease/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, bone fractures, and embryo-fetal toxicity.

The recommended dose is 160 mg orally once daily for 14 days then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

Sixty 40-mg capsules cost around $7,644, according to drugs.com. 
 

A version of this article appeared on Medscape.com.

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

The largest US physician organization wrestled with the professional risks and rewards of artificial intelligence (AI) at its annual meeting, delaying action even as it adopted new policies on prior authorization and other concerns for clinicians and patients.

Physicians and medical students at the annual meeting of the American Medical Association (AMA) House of Delegates in Chicago intensely debated a report and two key resolutions on AI but could not reach consensus, pushing off decision-making until a future meeting in November.

One resolution would establish “augmented intelligence” as the preferred term for AI, reflecting the desired role of these tools in supporting — not making — physicians’ decisions. The other resolution focused on insurers’ use of AI in determining medical necessity.

(See specific policies adopted at the meeting, held June 8-12, below.)

A comprehensive AMA trustees’ report on AI considered additional issues including requirements for disclosing AI use, liability for harms due to flawed application of AI, data privacy, and cybersecurity.

The AMA intends to “continue to methodically assess these issues and make informed recommendations in proposing new policy,” said Bobby Mukkamala, MD, an otolaryngologist from Flint, Michigan, who became the AMA’s new president-elect.

AMA members at the meeting largely applauded the aim of these AI proposals, but some objected to parts of the trustees’ report.

They raised questions about what, exactly, constitutes an AI-powered service and whether all AI tools need the kind of guardrails the AMA may seek. There also were concerns about calls to make AI use more transparent.

While transparency might be an admirable goal, it might prove too hard to achieve given that AI-powered tools and products are already woven into medical practice in ways that physicians may not know or understand, said Christopher Libby, MD, MPH, a clinical informaticist and emergency physician at Cedars Sinai Medical Center in Los Angeles.

“It’s hard for the practicing clinician to know how every piece of technology works in order to describe it to the patient,” Dr. Libby said at the meeting. “How many people here can identify when algorithms are used in their EHR today?”

He suggested asking for more transparency from the companies that make and sell AI-powered software and tools to insurers and healthcare systems.

Steven H. Kroft, MD, the editor of the American Journal of Clinical Pathology, raised concerns about the unintended harm that unchecked use of AI may pose to scientific research.

He asked the AMA to address “a significant omission in an otherwise comprehensive report” — the need to protect the integrity of study results that can direct patient care.

“While sham science is not a new issue, large language models make it far easier for authors to generate fake papers and far harder for editors, reviewers, and publishers to identify them,” Dr. Kroft said. “This is a rapidly growing phenomenon that is threatening the integrity of the literature. These papers become embedded in the evidence bases that drive clinical decision-making.”

AMA has been working with specialty societies and outside AI experts to refine an effective set of recommendations. The new policies, once finalized, are intended to build on steps AMA already has taken, including last year releasing principles for AI development, deployment, and use.
 

Congress Mulling

The AMA delegates are far from alone in facing AI policy challenges.

Leaders in Congress also are examining AI guardrails, with influential panels such as the Senate Finance and House Energy and Commerce committees holding hearings.

A key congressional AI effort to watch is the expected implementation of a bipartisan Senate “road map,” which Senate Majority Leader Chuck Schumer (D-NY) and colleagues released in May, said Miranda A. Franco, a senior policy advisor at the law firm Holland & Knight.

The product of many months of deliberation, this Senate road map identifies priorities for future legislation, including:

• Creating appropriate guardrails and safety measures to protect patients.
• Making healthcare and biomedical data available for machine learning and data science research while carefully addressing privacy issues.
• Providing transparency for clinicians and the public about the use of AI in medical products and clinical support services, including the data used to train models.
• Examining the Centers for Medicare & Medicaid Services’ reimbursement mechanisms as well as guardrails to ensure accountability, appropriate use, and broad application of AI across all populations.

Congress likely will address issues of AI in healthcare in piecemeal fashion, taking on different aspects of these challenges at different times, Ms. Franco said. The Senate road map gives the key committees directions on where to proceed in their efforts to develop new laws.

“I think this is all going to be slow and rolling, not big and sweeping,” Ms. Franco told this news organization. “I don’t think we’re going to see an encompassing AI bill.”
 

AMA Policies Adopted on Other Issues

At the June meeting, AMA delegates adopted the following policies aiming to:

• Increase oversight and accountability of health insurers’ use of prior authorization controls on patient access to care.
• Encourage policy changes allowing physicians to receive loan forgiveness when they practice in an Indian Health Service, Tribal, or Urban Indian Health Program, similar to physicians practicing in a Veterans Administration facility.
• Advocate for federal policy that limits a patient’s out-of-pocket cost to be the same or less than the amount that a patient with traditional Medicare plus a Medigap plan would pay.
• Oppose state or national legislation that could criminalize in vitro fertilization.
• Limit what the AMA calls the “expensive” cost for Medicare Advantage enrollees who need physician-administered drugs or biologics.
• Help physicians address the handling of de-identified patient data in a rapidly changing digital health ecosystem.
• Support efforts to decriminalize the possession of non-prescribed buprenorphine for personal use by individuals who lack access to a physician for the treatment of opioid use disorder.
• Expand access to hearing, vision, and dental care. The new AMA policy advocates working with state medical associations to support coverage of hearing exams, hearing aids, cochlear implants, and vision exams and aids. The revised AMA policy also supports working with the American Dental Association and other national organizations to improve access to dental care for people enrolled in Medicare, Medicaid, and CHIP programs.
• Increase enrollment of more women and sexual and gender minority populations in clinical trials.

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

The Comparison

A Plantar hyperpigmentation (benign ethnic melanosis) on the sole of the foot in a 62-year-old man of African descent with deeply pigmented skin. Dermoscopy showed a parallel ridge pattern even though the hyperpigmentation was benign (inset).

B Melanoma in situ with multicomponent hyperpigmentation on the sole of the foot in a 65-year-old Hispanic woman. Dermoscopy revealed a parallel ridge pattern (inset).

Plantar hyperpigmentation (also known as plantar melanosis [increased melanin], volar pigmented macules, benign racial melanosis, acral pigmentation, acral ethnic melanosis, or mottled hyperpigmentation of the plantar surface) is a benign finding in many individuals and is especially prevalent in those with darker skin tones. Acral refers to manifestation on the hands and feet, volar on the palms and soles, and plantar on the soles only. Here, we focus on plantar hyperpigmentation. We use the terms ethnic and racial interchangeably.

It is critically important to differentiate benign hyperpigmentation, which is common in patients with skin of color, from melanoma. Although rare, Black patients in the United States experience high morbidity and mortality from acral melanoma, which often is diagnosed late in the disease course.¹

There are many causes of hyperpigmentation on the plantar surfaces, including benign ethnic melanosis, nevi, melanoma, infections such as syphilis and tinea nigra, conditions such as Peutz-Jeghers syndrome and Laugier-Hunziker syndrome, and postinflammatory hyperpigmentation secondary to atopic dermatitis and psoriasis. We focus on the most common causes, ethnic melanosis and nevi, as well as melanoma, which is the deadliest cause.

Epidemiology

In a 1980 study (N=251), Black Americans had a high incidence of plantar hyperpigmentation, with 52% of affected patients having dark brown skin and 31% having light brown skin.²

The epidemiology of melanoma varies by race/ethnicity. Melanoma in Black individuals is relatively rare, with an annual incidence of approximately 1 in 100,000 individuals.³ However, when individuals with skin of color develop melanoma, they are more likely than their White counterparts to have acral melanoma (acral lentiginous melanoma), one of the deadliest types.¹ In a case series of Black patients with melanoma (N=48) from 2 tertiary care centers in Texas, 30 of 40 primary cutaneous melanomas (75%) were located on acral skin.⁴ Overall, 13 patients developed stage IV disease and 12 died due to disease progression. All patients who developed distant metastases or died of melanoma had acral melanoma.⁴ Individuals of Asian descent also have a high incidence of acral melanoma, as shown in research from Japan.^5-9

Key clinical features in individuals with darker skin tones

Dermoscopy is an evidence-based clinical examination method for earlier diagnosis of cutaneous melanoma, including on acral skin.^10,11 Benign nevi on the volar skin as well as the palms and soles tend to have one of these 3 dermoscopic patterns: parallel furrow, lattice, or irregular fibrillar. The pattern that is most predictive of volar melanoma is the parallel ridge pattern (PRP) (Figures A and B [insets]), which showed a high specificity (99.0%) and very high negative predictive value (97.7%) for malignant melanoma in a Japanese population.⁷ The PRP data from this study cannot be applied reliably to Black individuals, especially because benign ethnic melanosis and other benign conditions can demonstrate PRP.¹² Reliance on the PRP as a diagnostic clue could result in unneccessary biopsies in as many as 50% of Black patients with benign plantar hyperpigmentation.² Furthermore, biopsies of the plantar surface can be painful and cause pain while walking.

It has been suggested that PRP seen on dermoscopy in benign hyperpigmentation such as ethnic melanosis and nevi may preserve the acrosyringia (eccrine gland openings on the ridge), whereas PRP in melanoma may obliterate the acrosyringia.¹³ This observation is based on case reports only and needs further study. However, if validated, it could be a useful diagnostic clue.

Worth noting

In a retrospective cohort study of skin cancer in Black individuals (n=165) at a New York City–based cancer center from 2000 to 2020, 68% of patients were diagnosed with melanomas—80% were the acral subtype and 75% displayed a PRP. However, the surrounding uninvolved background skin, which was visible in most cases, also demonstrated a PRP.¹⁴ Because of the high morbidity and mortality rates of acral melanoma, clinicians should biopsy or immediately refer patients with concerning plantar hyperpigmentation to a dermatologist.

Health disparity highlight

The mortality rate for acral melanoma in Black patients is disproportionately high for the following reasons^15,16:

• Patients and health care providers do not expect to see melanoma in Black patients (it truly is rare!), so screening and education on sun protection are limited.
• Benign ethnic melanosis makes it more difficult to distinguish between early acral melanoma and benign skin changes.
• Black patients and other US patient populations with skin of color may be less likely to have health insurance, which contributes to inequities in access to health care. As of 2022, the uninsured rates for nonelderly American Indian and Alaska Native, Hispanic, Native Hawaiian and Other Pacific Islander, Black, and White individuals were 19.1%, 18.0%, 12.7%, 10.0%, and 6.6%, respectively.¹⁷

Multi-institutional registries could improve understanding of acral melanoma in Black patients.⁴ More studies are needed to help differentiate between the dermoscopic finding of PRP in benign ethnic melanosis vs malignant melanoma.

The Comparison

A Plantar hyperpigmentation (benign ethnic melanosis) on the sole of the foot in a 62-year-old man of African descent with deeply pigmented skin. Dermoscopy showed a parallel ridge pattern even though the hyperpigmentation was benign (inset).

B Melanoma in situ with multicomponent hyperpigmentation on the sole of the foot in a 65-year-old Hispanic woman. Dermoscopy revealed a parallel ridge pattern (inset).

Plantar hyperpigmentation (also known as plantar melanosis [increased melanin], volar pigmented macules, benign racial melanosis, acral pigmentation, acral ethnic melanosis, or mottled hyperpigmentation of the plantar surface) is a benign finding in many individuals and is especially prevalent in those with darker skin tones. Acral refers to manifestation on the hands and feet, volar on the palms and soles, and plantar on the soles only. Here, we focus on plantar hyperpigmentation. We use the terms ethnic and racial interchangeably.

It is critically important to differentiate benign hyperpigmentation, which is common in patients with skin of color, from melanoma. Although rare, Black patients in the United States experience high morbidity and mortality from acral melanoma, which often is diagnosed late in the disease course.¹

There are many causes of hyperpigmentation on the plantar surfaces, including benign ethnic melanosis, nevi, melanoma, infections such as syphilis and tinea nigra, conditions such as Peutz-Jeghers syndrome and Laugier-Hunziker syndrome, and postinflammatory hyperpigmentation secondary to atopic dermatitis and psoriasis. We focus on the most common causes, ethnic melanosis and nevi, as well as melanoma, which is the deadliest cause.

Epidemiology

In a 1980 study (N=251), Black Americans had a high incidence of plantar hyperpigmentation, with 52% of affected patients having dark brown skin and 31% having light brown skin.²

The epidemiology of melanoma varies by race/ethnicity. Melanoma in Black individuals is relatively rare, with an annual incidence of approximately 1 in 100,000 individuals.³ However, when individuals with skin of color develop melanoma, they are more likely than their White counterparts to have acral melanoma (acral lentiginous melanoma), one of the deadliest types.¹ In a case series of Black patients with melanoma (N=48) from 2 tertiary care centers in Texas, 30 of 40 primary cutaneous melanomas (75%) were located on acral skin.⁴ Overall, 13 patients developed stage IV disease and 12 died due to disease progression. All patients who developed distant metastases or died of melanoma had acral melanoma.⁴ Individuals of Asian descent also have a high incidence of acral melanoma, as shown in research from Japan.^5-9

Key clinical features in individuals with darker skin tones

Dermoscopy is an evidence-based clinical examination method for earlier diagnosis of cutaneous melanoma, including on acral skin.^10,11 Benign nevi on the volar skin as well as the palms and soles tend to have one of these 3 dermoscopic patterns: parallel furrow, lattice, or irregular fibrillar. The pattern that is most predictive of volar melanoma is the parallel ridge pattern (PRP) (Figures A and B [insets]), which showed a high specificity (99.0%) and very high negative predictive value (97.7%) for malignant melanoma in a Japanese population.⁷ The PRP data from this study cannot be applied reliably to Black individuals, especially because benign ethnic melanosis and other benign conditions can demonstrate PRP.¹² Reliance on the PRP as a diagnostic clue could result in unneccessary biopsies in as many as 50% of Black patients with benign plantar hyperpigmentation.² Furthermore, biopsies of the plantar surface can be painful and cause pain while walking.

It has been suggested that PRP seen on dermoscopy in benign hyperpigmentation such as ethnic melanosis and nevi may preserve the acrosyringia (eccrine gland openings on the ridge), whereas PRP in melanoma may obliterate the acrosyringia.¹³ This observation is based on case reports only and needs further study. However, if validated, it could be a useful diagnostic clue.

Worth noting

In a retrospective cohort study of skin cancer in Black individuals (n=165) at a New York City–based cancer center from 2000 to 2020, 68% of patients were diagnosed with melanomas—80% were the acral subtype and 75% displayed a PRP. However, the surrounding uninvolved background skin, which was visible in most cases, also demonstrated a PRP.¹⁴ Because of the high morbidity and mortality rates of acral melanoma, clinicians should biopsy or immediately refer patients with concerning plantar hyperpigmentation to a dermatologist.

Health disparity highlight

The mortality rate for acral melanoma in Black patients is disproportionately high for the following reasons^15,16:

• Patients and health care providers do not expect to see melanoma in Black patients (it truly is rare!), so screening and education on sun protection are limited.
• Benign ethnic melanosis makes it more difficult to distinguish between early acral melanoma and benign skin changes.
• Black patients and other US patient populations with skin of color may be less likely to have health insurance, which contributes to inequities in access to health care. As of 2022, the uninsured rates for nonelderly American Indian and Alaska Native, Hispanic, Native Hawaiian and Other Pacific Islander, Black, and White individuals were 19.1%, 18.0%, 12.7%, 10.0%, and 6.6%, respectively.¹⁷

Multi-institutional registries could improve understanding of acral melanoma in Black patients.⁴ More studies are needed to help differentiate between the dermoscopic finding of PRP in benign ethnic melanosis vs malignant melanoma.

The Comparison

A Plantar hyperpigmentation (benign ethnic melanosis) on the sole of the foot in a 62-year-old man of African descent with deeply pigmented skin. Dermoscopy showed a parallel ridge pattern even though the hyperpigmentation was benign (inset).

B Melanoma in situ with multicomponent hyperpigmentation on the sole of the foot in a 65-year-old Hispanic woman. Dermoscopy revealed a parallel ridge pattern (inset).

Plantar hyperpigmentation (also known as plantar melanosis [increased melanin], volar pigmented macules, benign racial melanosis, acral pigmentation, acral ethnic melanosis, or mottled hyperpigmentation of the plantar surface) is a benign finding in many individuals and is especially prevalent in those with darker skin tones. Acral refers to manifestation on the hands and feet, volar on the palms and soles, and plantar on the soles only. Here, we focus on plantar hyperpigmentation. We use the terms ethnic and racial interchangeably.

It is critically important to differentiate benign hyperpigmentation, which is common in patients with skin of color, from melanoma. Although rare, Black patients in the United States experience high morbidity and mortality from acral melanoma, which often is diagnosed late in the disease course.¹

There are many causes of hyperpigmentation on the plantar surfaces, including benign ethnic melanosis, nevi, melanoma, infections such as syphilis and tinea nigra, conditions such as Peutz-Jeghers syndrome and Laugier-Hunziker syndrome, and postinflammatory hyperpigmentation secondary to atopic dermatitis and psoriasis. We focus on the most common causes, ethnic melanosis and nevi, as well as melanoma, which is the deadliest cause.

Epidemiology

In a 1980 study (N=251), Black Americans had a high incidence of plantar hyperpigmentation, with 52% of affected patients having dark brown skin and 31% having light brown skin.²

The epidemiology of melanoma varies by race/ethnicity. Melanoma in Black individuals is relatively rare, with an annual incidence of approximately 1 in 100,000 individuals.³ However, when individuals with skin of color develop melanoma, they are more likely than their White counterparts to have acral melanoma (acral lentiginous melanoma), one of the deadliest types.¹ In a case series of Black patients with melanoma (N=48) from 2 tertiary care centers in Texas, 30 of 40 primary cutaneous melanomas (75%) were located on acral skin.⁴ Overall, 13 patients developed stage IV disease and 12 died due to disease progression. All patients who developed distant metastases or died of melanoma had acral melanoma.⁴ Individuals of Asian descent also have a high incidence of acral melanoma, as shown in research from Japan.^5-9

Key clinical features in individuals with darker skin tones

Dermoscopy is an evidence-based clinical examination method for earlier diagnosis of cutaneous melanoma, including on acral skin.^10,11 Benign nevi on the volar skin as well as the palms and soles tend to have one of these 3 dermoscopic patterns: parallel furrow, lattice, or irregular fibrillar. The pattern that is most predictive of volar melanoma is the parallel ridge pattern (PRP) (Figures A and B [insets]), which showed a high specificity (99.0%) and very high negative predictive value (97.7%) for malignant melanoma in a Japanese population.⁷ The PRP data from this study cannot be applied reliably to Black individuals, especially because benign ethnic melanosis and other benign conditions can demonstrate PRP.¹² Reliance on the PRP as a diagnostic clue could result in unneccessary biopsies in as many as 50% of Black patients with benign plantar hyperpigmentation.² Furthermore, biopsies of the plantar surface can be painful and cause pain while walking.

It has been suggested that PRP seen on dermoscopy in benign hyperpigmentation such as ethnic melanosis and nevi may preserve the acrosyringia (eccrine gland openings on the ridge), whereas PRP in melanoma may obliterate the acrosyringia.¹³ This observation is based on case reports only and needs further study. However, if validated, it could be a useful diagnostic clue.

Worth noting

In a retrospective cohort study of skin cancer in Black individuals (n=165) at a New York City–based cancer center from 2000 to 2020, 68% of patients were diagnosed with melanomas—80% were the acral subtype and 75% displayed a PRP. However, the surrounding uninvolved background skin, which was visible in most cases, also demonstrated a PRP.¹⁴ Because of the high morbidity and mortality rates of acral melanoma, clinicians should biopsy or immediately refer patients with concerning plantar hyperpigmentation to a dermatologist.

Health disparity highlight

The mortality rate for acral melanoma in Black patients is disproportionately high for the following reasons^15,16:

• Patients and health care providers do not expect to see melanoma in Black patients (it truly is rare!), so screening and education on sun protection are limited.
• Benign ethnic melanosis makes it more difficult to distinguish between early acral melanoma and benign skin changes.
• Black patients and other US patient populations with skin of color may be less likely to have health insurance, which contributes to inequities in access to health care. As of 2022, the uninsured rates for nonelderly American Indian and Alaska Native, Hispanic, Native Hawaiian and Other Pacific Islander, Black, and White individuals were 19.1%, 18.0%, 12.7%, 10.0%, and 6.6%, respectively.¹⁷

Multi-institutional registries could improve understanding of acral melanoma in Black patients.⁴ More studies are needed to help differentiate between the dermoscopic finding of PRP in benign ethnic melanosis vs malignant melanoma.

Minoxidil, a potent vasodilator, was approved by the US Food and Drug Administration (FDA) in 1963 to treat high blood pressure. Its application as a hair loss treatment was discovered by accident—patients taking oral minoxidil for blood pressure noticed hair growth on their bodies as a side effect of the medication. In 1988, topical minoxidil (Rogaine [Johnson & Johnson Consumer Inc]) was approved by the FDA for the treatment of androgenetic alopecia in men, and then it was approved for the same indication in women in 1991. The mechanism of action by which minoxidil increases hair growth still has not been fully elucidated. When applied topically, it is thought to extend the anagen phase (or growth phase) of the hair cycle and increase hair follicle size. It also increases oxygen to the hair follicle through vasodilation and stimulates the production of vascular endothelial growth factor, which is thought to promote hair growth.¹ Since its approval, topical minoxidil has become a first-line treatment of androgenetic alopecia in men and women.

In August 2022, The New York Times (NYT) published an article on dermatologists’ use of oral minoxidil at a fraction of the dose prescribed for blood pressure with profound results in hair regrowth.² Several dermatologists quoted in the article endorsed that the decreased dose minimizes unwanted side effects such as hypertrichosis, hypotension, and other cardiac issues while still being effective for hair loss. Also, compared to topical minoxidil, low-dose oral minoxidil (LDOM) is relatively cheaper and easier to use; topicals are more cumbersome to apply and often leave the hair and scalp sticky, leading to noncompliance among patients.² Currently, oral minoxidil is not approved by the FDA for use in hair loss, making it an off-label use.

Since the NYT article was published, we have observed an increase in patient questions and requests for LDOM as well as heightened use by fellow dermatologists in our community. As of November 2022, the NYT had approximately 9,330,000 total subscribers, solidifying its place as a newspaper of record in the United States and across the world.³ In April 2023, we conducted a survey of US-based board-certified dermatologists to investigate the impact of the NYT article on prescribing practices of LDOM for alopecia. The survey was conducted as a poll in a Facebook group for board-certified dermatologists and asked, “How did the NYT article on oral minoxidil for alopecia change your utilization of LDOM (low-dose oral minoxidil) for alopecia?” Three answer choices were given: (1) I started Rx’ing LDOM or increased the number of patients I manage with LDOM; (2) No change. I never Rx’d LDOM and/or no increase in utilization; and (3) I was already prescribing LDOM.

Of the 65 total respondents, 27 (42%) reported that the NYT article influenced their decision to start prescribing LDOM for alopecia. Nine respondents (14%) reported that the article did not influence their prescribing habits, and 27 (42%) responded that they were already prescribing the medication prior to the article’s publication.

Data from Epiphany Dermatology, a practice with more than 70 locations throughout the United States, showed that oral minoxidil was prescribed for alopecia 107 times in 2020 and 672 times in 2021 (Amy Hadley, Epiphany Dermatology, written communication, March 24, 2023). In 2022, prescriptions increased exponentially to 1626, and in the period of January 2023 to March 2023 alone, oral minoxidil was prescribed 510 times. Following publication of the NYT article in August 2022, LDOM was prescribed a total of 1377 times in the next 8 months.

Moreover, data from Summit Pharmacy, a retail pharmacy in Centennial, Colorado, showed an 1800% increase in LDOM prescriptions in the 7 months following the NYT article’s publication (August 2022 to March 2023) compared with the 7 months prior (January 2022 to August 2022)(Brandon Johnson, Summit Pharmacy, written communication, March 30, 2023). These data provide evidence for the influence of the NYT article on prescribing habits of dermatology providers in the United States.

The safety of oral minoxidil for use in hair loss has been established through several studies in the literature.^4,5 These results show that LDOM may be a safe, readily accessible, and revolutionary treatment for hair loss. A retrospective multicenter study of 1404 patients treated with LDOM for any type of alopecia found that side effects were infrequent, and only 1.7% of patients discontinued treatment due to adverse effects. The most frequent adverse effect was hypertrichosis, occurring in 15.1% of patients but leading to treatment withdrawal in only 0.5% of patients.⁴ Similarly, Randolph and Tosti⁵ found that hypertrichosis of the face and body was the most common adverse effect observed, though it rarely resulted in discontinuation and likely was dose dependent: less than 10% of patients receiving 0.25 mg/d experienced hypertrichosis compared with more than 50% of those receiving 5 mg/d (N=634). They also described patients in whom topical minoxidil, though effective, posed major barriers to compliance due to the twice-daily application, changes to hair texture from the medication, and scalp irritation. A literature review of 17 studies with 634 patients on LDOM as a primary treatment for hair loss found that it was an effective, well-tolerated treatment and should be considered for healthy patients who have difficulty with topical formulations.⁵

In the age of media with data constantly at users’ fingertips, the art of practicing medicine also has changed. Although physicians pride themselves on evidence-based medicine, it appears that an NYT article had an impact on how physicians, particularly dermatologists, prescribe oral minoxidil. However, it is difficult to know if the article exposed dermatologists to another treatment in their armamentarium for hair loss or if it influenced patients to ask their health care provider about LDOM for hair loss. One thing is clear—since the article’s publication, the off-label use of LDOM for alopecia has produced what many may call “miracles” for patients with hair loss.⁵

Minoxidil, a potent vasodilator, was approved by the US Food and Drug Administration (FDA) in 1963 to treat high blood pressure. Its application as a hair loss treatment was discovered by accident—patients taking oral minoxidil for blood pressure noticed hair growth on their bodies as a side effect of the medication. In 1988, topical minoxidil (Rogaine [Johnson & Johnson Consumer Inc]) was approved by the FDA for the treatment of androgenetic alopecia in men, and then it was approved for the same indication in women in 1991. The mechanism of action by which minoxidil increases hair growth still has not been fully elucidated. When applied topically, it is thought to extend the anagen phase (or growth phase) of the hair cycle and increase hair follicle size. It also increases oxygen to the hair follicle through vasodilation and stimulates the production of vascular endothelial growth factor, which is thought to promote hair growth.¹ Since its approval, topical minoxidil has become a first-line treatment of androgenetic alopecia in men and women.

In August 2022, The New York Times (NYT) published an article on dermatologists’ use of oral minoxidil at a fraction of the dose prescribed for blood pressure with profound results in hair regrowth.² Several dermatologists quoted in the article endorsed that the decreased dose minimizes unwanted side effects such as hypertrichosis, hypotension, and other cardiac issues while still being effective for hair loss. Also, compared to topical minoxidil, low-dose oral minoxidil (LDOM) is relatively cheaper and easier to use; topicals are more cumbersome to apply and often leave the hair and scalp sticky, leading to noncompliance among patients.² Currently, oral minoxidil is not approved by the FDA for use in hair loss, making it an off-label use.

Since the NYT article was published, we have observed an increase in patient questions and requests for LDOM as well as heightened use by fellow dermatologists in our community. As of November 2022, the NYT had approximately 9,330,000 total subscribers, solidifying its place as a newspaper of record in the United States and across the world.³ In April 2023, we conducted a survey of US-based board-certified dermatologists to investigate the impact of the NYT article on prescribing practices of LDOM for alopecia. The survey was conducted as a poll in a Facebook group for board-certified dermatologists and asked, “How did the NYT article on oral minoxidil for alopecia change your utilization of LDOM (low-dose oral minoxidil) for alopecia?” Three answer choices were given: (1) I started Rx’ing LDOM or increased the number of patients I manage with LDOM; (2) No change. I never Rx’d LDOM and/or no increase in utilization; and (3) I was already prescribing LDOM.

Of the 65 total respondents, 27 (42%) reported that the NYT article influenced their decision to start prescribing LDOM for alopecia. Nine respondents (14%) reported that the article did not influence their prescribing habits, and 27 (42%) responded that they were already prescribing the medication prior to the article’s publication.

Data from Epiphany Dermatology, a practice with more than 70 locations throughout the United States, showed that oral minoxidil was prescribed for alopecia 107 times in 2020 and 672 times in 2021 (Amy Hadley, Epiphany Dermatology, written communication, March 24, 2023). In 2022, prescriptions increased exponentially to 1626, and in the period of January 2023 to March 2023 alone, oral minoxidil was prescribed 510 times. Following publication of the NYT article in August 2022, LDOM was prescribed a total of 1377 times in the next 8 months.

Moreover, data from Summit Pharmacy, a retail pharmacy in Centennial, Colorado, showed an 1800% increase in LDOM prescriptions in the 7 months following the NYT article’s publication (August 2022 to March 2023) compared with the 7 months prior (January 2022 to August 2022)(Brandon Johnson, Summit Pharmacy, written communication, March 30, 2023). These data provide evidence for the influence of the NYT article on prescribing habits of dermatology providers in the United States.

The safety of oral minoxidil for use in hair loss has been established through several studies in the literature.^4,5 These results show that LDOM may be a safe, readily accessible, and revolutionary treatment for hair loss. A retrospective multicenter study of 1404 patients treated with LDOM for any type of alopecia found that side effects were infrequent, and only 1.7% of patients discontinued treatment due to adverse effects. The most frequent adverse effect was hypertrichosis, occurring in 15.1% of patients but leading to treatment withdrawal in only 0.5% of patients.⁴ Similarly, Randolph and Tosti⁵ found that hypertrichosis of the face and body was the most common adverse effect observed, though it rarely resulted in discontinuation and likely was dose dependent: less than 10% of patients receiving 0.25 mg/d experienced hypertrichosis compared with more than 50% of those receiving 5 mg/d (N=634). They also described patients in whom topical minoxidil, though effective, posed major barriers to compliance due to the twice-daily application, changes to hair texture from the medication, and scalp irritation. A literature review of 17 studies with 634 patients on LDOM as a primary treatment for hair loss found that it was an effective, well-tolerated treatment and should be considered for healthy patients who have difficulty with topical formulations.⁵

In the age of media with data constantly at users’ fingertips, the art of practicing medicine also has changed. Although physicians pride themselves on evidence-based medicine, it appears that an NYT article had an impact on how physicians, particularly dermatologists, prescribe oral minoxidil. However, it is difficult to know if the article exposed dermatologists to another treatment in their armamentarium for hair loss or if it influenced patients to ask their health care provider about LDOM for hair loss. One thing is clear—since the article’s publication, the off-label use of LDOM for alopecia has produced what many may call “miracles” for patients with hair loss.⁵

Minoxidil, a potent vasodilator, was approved by the US Food and Drug Administration (FDA) in 1963 to treat high blood pressure. Its application as a hair loss treatment was discovered by accident—patients taking oral minoxidil for blood pressure noticed hair growth on their bodies as a side effect of the medication. In 1988, topical minoxidil (Rogaine [Johnson & Johnson Consumer Inc]) was approved by the FDA for the treatment of androgenetic alopecia in men, and then it was approved for the same indication in women in 1991. The mechanism of action by which minoxidil increases hair growth still has not been fully elucidated. When applied topically, it is thought to extend the anagen phase (or growth phase) of the hair cycle and increase hair follicle size. It also increases oxygen to the hair follicle through vasodilation and stimulates the production of vascular endothelial growth factor, which is thought to promote hair growth.¹ Since its approval, topical minoxidil has become a first-line treatment of androgenetic alopecia in men and women.

In August 2022, The New York Times (NYT) published an article on dermatologists’ use of oral minoxidil at a fraction of the dose prescribed for blood pressure with profound results in hair regrowth.² Several dermatologists quoted in the article endorsed that the decreased dose minimizes unwanted side effects such as hypertrichosis, hypotension, and other cardiac issues while still being effective for hair loss. Also, compared to topical minoxidil, low-dose oral minoxidil (LDOM) is relatively cheaper and easier to use; topicals are more cumbersome to apply and often leave the hair and scalp sticky, leading to noncompliance among patients.² Currently, oral minoxidil is not approved by the FDA for use in hair loss, making it an off-label use.

Since the NYT article was published, we have observed an increase in patient questions and requests for LDOM as well as heightened use by fellow dermatologists in our community. As of November 2022, the NYT had approximately 9,330,000 total subscribers, solidifying its place as a newspaper of record in the United States and across the world.³ In April 2023, we conducted a survey of US-based board-certified dermatologists to investigate the impact of the NYT article on prescribing practices of LDOM for alopecia. The survey was conducted as a poll in a Facebook group for board-certified dermatologists and asked, “How did the NYT article on oral minoxidil for alopecia change your utilization of LDOM (low-dose oral minoxidil) for alopecia?” Three answer choices were given: (1) I started Rx’ing LDOM or increased the number of patients I manage with LDOM; (2) No change. I never Rx’d LDOM and/or no increase in utilization; and (3) I was already prescribing LDOM.

Of the 65 total respondents, 27 (42%) reported that the NYT article influenced their decision to start prescribing LDOM for alopecia. Nine respondents (14%) reported that the article did not influence their prescribing habits, and 27 (42%) responded that they were already prescribing the medication prior to the article’s publication.

Data from Epiphany Dermatology, a practice with more than 70 locations throughout the United States, showed that oral minoxidil was prescribed for alopecia 107 times in 2020 and 672 times in 2021 (Amy Hadley, Epiphany Dermatology, written communication, March 24, 2023). In 2022, prescriptions increased exponentially to 1626, and in the period of January 2023 to March 2023 alone, oral minoxidil was prescribed 510 times. Following publication of the NYT article in August 2022, LDOM was prescribed a total of 1377 times in the next 8 months.

Moreover, data from Summit Pharmacy, a retail pharmacy in Centennial, Colorado, showed an 1800% increase in LDOM prescriptions in the 7 months following the NYT article’s publication (August 2022 to March 2023) compared with the 7 months prior (January 2022 to August 2022)(Brandon Johnson, Summit Pharmacy, written communication, March 30, 2023). These data provide evidence for the influence of the NYT article on prescribing habits of dermatology providers in the United States.

The safety of oral minoxidil for use in hair loss has been established through several studies in the literature.^4,5 These results show that LDOM may be a safe, readily accessible, and revolutionary treatment for hair loss. A retrospective multicenter study of 1404 patients treated with LDOM for any type of alopecia found that side effects were infrequent, and only 1.7% of patients discontinued treatment due to adverse effects. The most frequent adverse effect was hypertrichosis, occurring in 15.1% of patients but leading to treatment withdrawal in only 0.5% of patients.⁴ Similarly, Randolph and Tosti⁵ found that hypertrichosis of the face and body was the most common adverse effect observed, though it rarely resulted in discontinuation and likely was dose dependent: less than 10% of patients receiving 0.25 mg/d experienced hypertrichosis compared with more than 50% of those receiving 5 mg/d (N=634). They also described patients in whom topical minoxidil, though effective, posed major barriers to compliance due to the twice-daily application, changes to hair texture from the medication, and scalp irritation. A literature review of 17 studies with 634 patients on LDOM as a primary treatment for hair loss found that it was an effective, well-tolerated treatment and should be considered for healthy patients who have difficulty with topical formulations.⁵

In the age of media with data constantly at users’ fingertips, the art of practicing medicine also has changed. Although physicians pride themselves on evidence-based medicine, it appears that an NYT article had an impact on how physicians, particularly dermatologists, prescribe oral minoxidil. However, it is difficult to know if the article exposed dermatologists to another treatment in their armamentarium for hair loss or if it influenced patients to ask their health care provider about LDOM for hair loss. One thing is clear—since the article’s publication, the off-label use of LDOM for alopecia has produced what many may call “miracles” for patients with hair loss.⁵

Sea urchins—members of the phylum Echinodermata and the class Echinoidea—are spiny marine invertebrates. Their consumption of fleshy algae makes them essential players in maintaining reef ecosystems.^1,2 Echinoids, a class that includes heart urchins and sand dollars, are ubiquitous in benthic marine environments, both free floating and rock boring, and inhabit a wide range of latitudes spanning from polar oceans to warm seas.³ Despite their immobility and nonaggression, sea urchin puncture wounds are common among divers, snorkelers, swimmers, surfers, and fishers who accidentally come into contact with their sharp spines. Although the epidemiology of sea urchin exposure and injury is difficult to assess, the American Association of Poison Control Centers’ most recent annual report in 2022 documents approximately 1426 annual aquatic bites and/or envenomations.⁴

Sea Urchin Morphology and Toxicity

Echinoderms (a term of Greek origin meaning spiny skin) share a radially symmetric calcium carbonate skeleton (termed stereom) that is supported by collagenous ligaments.¹ Sea urchins possess spines composed of calcite crystals, which radiate from their body and play a role in locomotion and defense against predators—namely sea otters, starfish/sea stars, wolf eels, and triggerfish, among others (Figure).⁵ These brittle spines can easily penetrate human skin and subsequently break off the sea urchin body. Most species of sea urchins possess solid spines, but a small percentage (80 of approximately 700 extant species) have hollow spines containing various toxic substances.⁶ Penetration and systemic absorption of the toxins within these spines can generate severe systemic responses.

The venomous flower urchin (Toxopneustes pileolus), found in the Indian and Pacific oceans, is one of the more common species known to produce a systemic reaction involving neuromuscular blockage.^7-9 The most common species harvested off the Pacific coast of the United States—Strongylocentrotus purpuratus (purple sea urchin) and Strongylocentrotus franciscanus (red sea urchins)—are not inherently venomous.⁸

Presentation and Diagnosis of Sea Urchin Injuries

Sea urchin injuries have a wide range of manifestations depending on the number of spines involved, the presence of venom, the depth and location of spine penetration, the duration of spine retention in the skin, and the time before treatment initiation. The most common site of sea urchin injury unsurprisingly is the lower extremities and feet, often in the context of divers and swimmers walking across the sea floor. The hands are another frequently injured site, along with the legs, arms, back, scalp, and even oral mucosa.¹¹

Although clinical history and presentation frequently reveal the mechanism of aquatic injury, patients often are unsure of the agent to which they were exposed and may be unaware of retained foreign bodies. Dermoscopy can distinguish the distinct lines radiating from the core of sea urchin spines from other foreign bodies lodged within the skin.⁶ It also can be used to locate spines for removal or for their analysis following punch biopsy.^6,12 The radiopaque nature of sea urchin spines makes radiography and magnetic resonance imaging useful tools in assessment of periarticular soft-tissue damage and spine removal.^8,11,13 Ultrasonography can reveal spines that no longer appear on radiography due to absorption by human tissue.¹⁴

Immediate Dermatologic Effects

Sea urchin injuries can be broadly categorized into immediate and delayed reactions. Immediate manifestations of contact with sea urchin spines include localized pain, bleeding, erythema, myalgia, and edema at the site of injury that can last from a few hours to 1 week without proper wound care and spine removal.⁵ Systemic symptoms ranging from dizziness, lightheadedness, paresthesia, aphonia, paralysis, coma, and death generally are only seen following injuries from venomous species, attachment of pedicellariae, injuries involving neurovascular structures, or penetration by more than 15 spines.^7,11

Initial treatment includes soaking the wound in hot water (113 °F [45 °C]) for 30 to 90 minutes and subsequently removing spines and pedicellariae to prevent development of delayed reactions.^5,15,16 The compounds in the sea urchin epithelium are heat labile and will be inactivated upon soaking in hot water.¹⁶ Extraction of spines can be difficult, as they are brittle and easily break in the skin. Successful removal has been reported using forceps and a hypodermic needle as well as excision; both approaches may require local anesthesia.^8,17 Another technique involves freezing the localized area with liquid nitrogen to allow easier removal upon skin blistering.¹⁸ Punch biopsy also has been utilized as an effective means of ensuring all spiny fragments are removed.^9,19,20 These spines often cause black or purple tattoolike staining at the puncture site, which can persist for a few days after spine extraction.⁸ Ablation using the erbium-doped:YAG laser may be helpful for removal of associated pigment.^21,22

Delayed Dermatologic Effects

Delayed reactions to sea urchin injuries often are attributable to prolonged retention of spines in the skin. Granulomatous reactions typically manifest 2 weeks after injury as firm nonsuppurative nodules with central umbilication and a hyperkeratotic surface.⁷ These nodules may or may not be painful. Histopathology most often reveals foreign body and sarcoidal-type granulomatous reactions. However, tuberculoid, necrobiotic, and suppurative granulomas also may develop.¹³ Other microscopic features include inflammatory reactions, suppurative dermatitis, focal necrosis, and microabscesses.²³ Wounds with progression to granulomatous disease often require surgical debridement.

Other more serious sequalae can result from involvement of joint capsules, especially in the hands and feet. Sea urchin injury involving joint spaces should be treated aggressively, as progression to inflammatory or infectious synovitis and tenosynovitis can cause irreversible loss of joint function. Inflammatory synovitis occurs 1 to 2 months on average after injury following a period of minimal symptoms and begins as a gradual increase in joint swelling and decrease in range of motion.⁸ Infectious tenosynovitis manifests quite similarly. Although suppurative etiologies generally progress with a more acute onset, certain infectious organisms (eg, Mycobacterium) take on an indolent course and should not be overlooked as a cause of delayed symptoms.⁸ The Kavanel cardinal signs are a sensitive tool used in the diagnosis of infectious flexor sheath tenosynovitis.^8,24 If suspicion for joint infection is high, emergency referral should be made for debridement and culture-guided antibiotic therapy. Left untreated, infectious tenosynovitis can result in tendon necrosis or rupture, digit necrosis, and systemic infection.²⁴ Patients with joint involvement should be referred to specialty care (eg, hand surgeon), as they often require synovectomy and surgical removal of foreign material.⁸

From 1 month to 1 year after injury, prolonged granulomatous synovitis of the hand may eventually lead to joint destruction known as “sea urchin arthritis.” These patients present with decreased range of motion and numerous nodules on the hand with a hyperkeratotic surface. Radiography reveals joint space narrowing, osteolysis, subchondral sclerosis, and periosteal reaction. Synovectomy and debridement are necessary to prevent irreversible joint damage or the need for arthrodesis and bone grafting.²⁴

Other Treatment Considerations

Other important considerations in the care of sea urchin spine injuries include assessment of tetanus immunization status and administration of necessary prophylaxis as soon as possible, even in delayed presentations (Table).^16,25 Cultures should be taken only if infection is suspected. Prophylactic antibiotics are not recommended unless the patient is immunocompromised or otherwise has impaired wound healing. If a patient presents with systemic symptoms, they should be referred to an emergency care facility for further management.

Final Thoughts

Sea urchin injuries can lead to serious complications if not diagnosed quickly and treated properly. Retention of sea urchin spines in the deep tissues and joint spaces may lead to granulomas, inflammatory and infectious tenosynovitis (including mycobacterial infection), and sea urchin arthritis requiring surgical debridement and possible irreversible joint damage, up to a year after initial injury. Patients should be educated on the possibility of developing these delayed reactions and instructed to seek immediate care. Joint deformities, range-of-motion deficits, and involvement of neurovascular structures should be considered emergent and referred for proper management. Shoes and diving gear offer some protection but are easily penetrable by sharp sea urchin spines. Preventive focus should be aimed at educating patients and providers on the importance of prompt spine removal upon injury. Although dermatologic and systemic manifestations vary widely, a thorough history, physical examination, and appropriate use of imaging modalities can facilitate accurate diagnosis and guide treatment.

Sea urchins—members of the phylum Echinodermata and the class Echinoidea—are spiny marine invertebrates. Their consumption of fleshy algae makes them essential players in maintaining reef ecosystems.^1,2 Echinoids, a class that includes heart urchins and sand dollars, are ubiquitous in benthic marine environments, both free floating and rock boring, and inhabit a wide range of latitudes spanning from polar oceans to warm seas.³ Despite their immobility and nonaggression, sea urchin puncture wounds are common among divers, snorkelers, swimmers, surfers, and fishers who accidentally come into contact with their sharp spines. Although the epidemiology of sea urchin exposure and injury is difficult to assess, the American Association of Poison Control Centers’ most recent annual report in 2022 documents approximately 1426 annual aquatic bites and/or envenomations.⁴

Sea Urchin Morphology and Toxicity

Echinoderms (a term of Greek origin meaning spiny skin) share a radially symmetric calcium carbonate skeleton (termed stereom) that is supported by collagenous ligaments.¹ Sea urchins possess spines composed of calcite crystals, which radiate from their body and play a role in locomotion and defense against predators—namely sea otters, starfish/sea stars, wolf eels, and triggerfish, among others (Figure).⁵ These brittle spines can easily penetrate human skin and subsequently break off the sea urchin body. Most species of sea urchins possess solid spines, but a small percentage (80 of approximately 700 extant species) have hollow spines containing various toxic substances.⁶ Penetration and systemic absorption of the toxins within these spines can generate severe systemic responses.

The venomous flower urchin (Toxopneustes pileolus), found in the Indian and Pacific oceans, is one of the more common species known to produce a systemic reaction involving neuromuscular blockage.^7-9 The most common species harvested off the Pacific coast of the United States—Strongylocentrotus purpuratus (purple sea urchin) and Strongylocentrotus franciscanus (red sea urchins)—are not inherently venomous.⁸

Presentation and Diagnosis of Sea Urchin Injuries

Sea urchin injuries have a wide range of manifestations depending on the number of spines involved, the presence of venom, the depth and location of spine penetration, the duration of spine retention in the skin, and the time before treatment initiation. The most common site of sea urchin injury unsurprisingly is the lower extremities and feet, often in the context of divers and swimmers walking across the sea floor. The hands are another frequently injured site, along with the legs, arms, back, scalp, and even oral mucosa.¹¹

Although clinical history and presentation frequently reveal the mechanism of aquatic injury, patients often are unsure of the agent to which they were exposed and may be unaware of retained foreign bodies. Dermoscopy can distinguish the distinct lines radiating from the core of sea urchin spines from other foreign bodies lodged within the skin.⁶ It also can be used to locate spines for removal or for their analysis following punch biopsy.^6,12 The radiopaque nature of sea urchin spines makes radiography and magnetic resonance imaging useful tools in assessment of periarticular soft-tissue damage and spine removal.^8,11,13 Ultrasonography can reveal spines that no longer appear on radiography due to absorption by human tissue.¹⁴

Immediate Dermatologic Effects

Sea urchin injuries can be broadly categorized into immediate and delayed reactions. Immediate manifestations of contact with sea urchin spines include localized pain, bleeding, erythema, myalgia, and edema at the site of injury that can last from a few hours to 1 week without proper wound care and spine removal.⁵ Systemic symptoms ranging from dizziness, lightheadedness, paresthesia, aphonia, paralysis, coma, and death generally are only seen following injuries from venomous species, attachment of pedicellariae, injuries involving neurovascular structures, or penetration by more than 15 spines.^7,11

Initial treatment includes soaking the wound in hot water (113 °F [45 °C]) for 30 to 90 minutes and subsequently removing spines and pedicellariae to prevent development of delayed reactions.^5,15,16 The compounds in the sea urchin epithelium are heat labile and will be inactivated upon soaking in hot water.¹⁶ Extraction of spines can be difficult, as they are brittle and easily break in the skin. Successful removal has been reported using forceps and a hypodermic needle as well as excision; both approaches may require local anesthesia.^8,17 Another technique involves freezing the localized area with liquid nitrogen to allow easier removal upon skin blistering.¹⁸ Punch biopsy also has been utilized as an effective means of ensuring all spiny fragments are removed.^9,19,20 These spines often cause black or purple tattoolike staining at the puncture site, which can persist for a few days after spine extraction.⁸ Ablation using the erbium-doped:YAG laser may be helpful for removal of associated pigment.^21,22

Delayed Dermatologic Effects

Delayed reactions to sea urchin injuries often are attributable to prolonged retention of spines in the skin. Granulomatous reactions typically manifest 2 weeks after injury as firm nonsuppurative nodules with central umbilication and a hyperkeratotic surface.⁷ These nodules may or may not be painful. Histopathology most often reveals foreign body and sarcoidal-type granulomatous reactions. However, tuberculoid, necrobiotic, and suppurative granulomas also may develop.¹³ Other microscopic features include inflammatory reactions, suppurative dermatitis, focal necrosis, and microabscesses.²³ Wounds with progression to granulomatous disease often require surgical debridement.

Other more serious sequalae can result from involvement of joint capsules, especially in the hands and feet. Sea urchin injury involving joint spaces should be treated aggressively, as progression to inflammatory or infectious synovitis and tenosynovitis can cause irreversible loss of joint function. Inflammatory synovitis occurs 1 to 2 months on average after injury following a period of minimal symptoms and begins as a gradual increase in joint swelling and decrease in range of motion.⁸ Infectious tenosynovitis manifests quite similarly. Although suppurative etiologies generally progress with a more acute onset, certain infectious organisms (eg, Mycobacterium) take on an indolent course and should not be overlooked as a cause of delayed symptoms.⁸ The Kavanel cardinal signs are a sensitive tool used in the diagnosis of infectious flexor sheath tenosynovitis.^8,24 If suspicion for joint infection is high, emergency referral should be made for debridement and culture-guided antibiotic therapy. Left untreated, infectious tenosynovitis can result in tendon necrosis or rupture, digit necrosis, and systemic infection.²⁴ Patients with joint involvement should be referred to specialty care (eg, hand surgeon), as they often require synovectomy and surgical removal of foreign material.⁸

From 1 month to 1 year after injury, prolonged granulomatous synovitis of the hand may eventually lead to joint destruction known as “sea urchin arthritis.” These patients present with decreased range of motion and numerous nodules on the hand with a hyperkeratotic surface. Radiography reveals joint space narrowing, osteolysis, subchondral sclerosis, and periosteal reaction. Synovectomy and debridement are necessary to prevent irreversible joint damage or the need for arthrodesis and bone grafting.²⁴

Other Treatment Considerations

Other important considerations in the care of sea urchin spine injuries include assessment of tetanus immunization status and administration of necessary prophylaxis as soon as possible, even in delayed presentations (Table).^16,25 Cultures should be taken only if infection is suspected. Prophylactic antibiotics are not recommended unless the patient is immunocompromised or otherwise has impaired wound healing. If a patient presents with systemic symptoms, they should be referred to an emergency care facility for further management.

Final Thoughts

Sea urchin injuries can lead to serious complications if not diagnosed quickly and treated properly. Retention of sea urchin spines in the deep tissues and joint spaces may lead to granulomas, inflammatory and infectious tenosynovitis (including mycobacterial infection), and sea urchin arthritis requiring surgical debridement and possible irreversible joint damage, up to a year after initial injury. Patients should be educated on the possibility of developing these delayed reactions and instructed to seek immediate care. Joint deformities, range-of-motion deficits, and involvement of neurovascular structures should be considered emergent and referred for proper management. Shoes and diving gear offer some protection but are easily penetrable by sharp sea urchin spines. Preventive focus should be aimed at educating patients and providers on the importance of prompt spine removal upon injury. Although dermatologic and systemic manifestations vary widely, a thorough history, physical examination, and appropriate use of imaging modalities can facilitate accurate diagnosis and guide treatment.

Sea urchins—members of the phylum Echinodermata and the class Echinoidea—are spiny marine invertebrates. Their consumption of fleshy algae makes them essential players in maintaining reef ecosystems.^1,2 Echinoids, a class that includes heart urchins and sand dollars, are ubiquitous in benthic marine environments, both free floating and rock boring, and inhabit a wide range of latitudes spanning from polar oceans to warm seas.³ Despite their immobility and nonaggression, sea urchin puncture wounds are common among divers, snorkelers, swimmers, surfers, and fishers who accidentally come into contact with their sharp spines. Although the epidemiology of sea urchin exposure and injury is difficult to assess, the American Association of Poison Control Centers’ most recent annual report in 2022 documents approximately 1426 annual aquatic bites and/or envenomations.⁴

Sea Urchin Morphology and Toxicity

Echinoderms (a term of Greek origin meaning spiny skin) share a radially symmetric calcium carbonate skeleton (termed stereom) that is supported by collagenous ligaments.¹ Sea urchins possess spines composed of calcite crystals, which radiate from their body and play a role in locomotion and defense against predators—namely sea otters, starfish/sea stars, wolf eels, and triggerfish, among others (Figure).⁵ These brittle spines can easily penetrate human skin and subsequently break off the sea urchin body. Most species of sea urchins possess solid spines, but a small percentage (80 of approximately 700 extant species) have hollow spines containing various toxic substances.⁶ Penetration and systemic absorption of the toxins within these spines can generate severe systemic responses.

The venomous flower urchin (Toxopneustes pileolus), found in the Indian and Pacific oceans, is one of the more common species known to produce a systemic reaction involving neuromuscular blockage.^7-9 The most common species harvested off the Pacific coast of the United States—Strongylocentrotus purpuratus (purple sea urchin) and Strongylocentrotus franciscanus (red sea urchins)—are not inherently venomous.⁸

Presentation and Diagnosis of Sea Urchin Injuries

Sea urchin injuries have a wide range of manifestations depending on the number of spines involved, the presence of venom, the depth and location of spine penetration, the duration of spine retention in the skin, and the time before treatment initiation. The most common site of sea urchin injury unsurprisingly is the lower extremities and feet, often in the context of divers and swimmers walking across the sea floor. The hands are another frequently injured site, along with the legs, arms, back, scalp, and even oral mucosa.¹¹

Although clinical history and presentation frequently reveal the mechanism of aquatic injury, patients often are unsure of the agent to which they were exposed and may be unaware of retained foreign bodies. Dermoscopy can distinguish the distinct lines radiating from the core of sea urchin spines from other foreign bodies lodged within the skin.⁶ It also can be used to locate spines for removal or for their analysis following punch biopsy.^6,12 The radiopaque nature of sea urchin spines makes radiography and magnetic resonance imaging useful tools in assessment of periarticular soft-tissue damage and spine removal.^8,11,13 Ultrasonography can reveal spines that no longer appear on radiography due to absorption by human tissue.¹⁴

Immediate Dermatologic Effects

Sea urchin injuries can be broadly categorized into immediate and delayed reactions. Immediate manifestations of contact with sea urchin spines include localized pain, bleeding, erythema, myalgia, and edema at the site of injury that can last from a few hours to 1 week without proper wound care and spine removal.⁵ Systemic symptoms ranging from dizziness, lightheadedness, paresthesia, aphonia, paralysis, coma, and death generally are only seen following injuries from venomous species, attachment of pedicellariae, injuries involving neurovascular structures, or penetration by more than 15 spines.^7,11

Initial treatment includes soaking the wound in hot water (113 °F [45 °C]) for 30 to 90 minutes and subsequently removing spines and pedicellariae to prevent development of delayed reactions.^5,15,16 The compounds in the sea urchin epithelium are heat labile and will be inactivated upon soaking in hot water.¹⁶ Extraction of spines can be difficult, as they are brittle and easily break in the skin. Successful removal has been reported using forceps and a hypodermic needle as well as excision; both approaches may require local anesthesia.^8,17 Another technique involves freezing the localized area with liquid nitrogen to allow easier removal upon skin blistering.¹⁸ Punch biopsy also has been utilized as an effective means of ensuring all spiny fragments are removed.^9,19,20 These spines often cause black or purple tattoolike staining at the puncture site, which can persist for a few days after spine extraction.⁸ Ablation using the erbium-doped:YAG laser may be helpful for removal of associated pigment.^21,22

Delayed Dermatologic Effects

Delayed reactions to sea urchin injuries often are attributable to prolonged retention of spines in the skin. Granulomatous reactions typically manifest 2 weeks after injury as firm nonsuppurative nodules with central umbilication and a hyperkeratotic surface.⁷ These nodules may or may not be painful. Histopathology most often reveals foreign body and sarcoidal-type granulomatous reactions. However, tuberculoid, necrobiotic, and suppurative granulomas also may develop.¹³ Other microscopic features include inflammatory reactions, suppurative dermatitis, focal necrosis, and microabscesses.²³ Wounds with progression to granulomatous disease often require surgical debridement.

Other more serious sequalae can result from involvement of joint capsules, especially in the hands and feet. Sea urchin injury involving joint spaces should be treated aggressively, as progression to inflammatory or infectious synovitis and tenosynovitis can cause irreversible loss of joint function. Inflammatory synovitis occurs 1 to 2 months on average after injury following a period of minimal symptoms and begins as a gradual increase in joint swelling and decrease in range of motion.⁸ Infectious tenosynovitis manifests quite similarly. Although suppurative etiologies generally progress with a more acute onset, certain infectious organisms (eg, Mycobacterium) take on an indolent course and should not be overlooked as a cause of delayed symptoms.⁸ The Kavanel cardinal signs are a sensitive tool used in the diagnosis of infectious flexor sheath tenosynovitis.^8,24 If suspicion for joint infection is high, emergency referral should be made for debridement and culture-guided antibiotic therapy. Left untreated, infectious tenosynovitis can result in tendon necrosis or rupture, digit necrosis, and systemic infection.²⁴ Patients with joint involvement should be referred to specialty care (eg, hand surgeon), as they often require synovectomy and surgical removal of foreign material.⁸

From 1 month to 1 year after injury, prolonged granulomatous synovitis of the hand may eventually lead to joint destruction known as “sea urchin arthritis.” These patients present with decreased range of motion and numerous nodules on the hand with a hyperkeratotic surface. Radiography reveals joint space narrowing, osteolysis, subchondral sclerosis, and periosteal reaction. Synovectomy and debridement are necessary to prevent irreversible joint damage or the need for arthrodesis and bone grafting.²⁴

Other Treatment Considerations

Other important considerations in the care of sea urchin spine injuries include assessment of tetanus immunization status and administration of necessary prophylaxis as soon as possible, even in delayed presentations (Table).^16,25 Cultures should be taken only if infection is suspected. Prophylactic antibiotics are not recommended unless the patient is immunocompromised or otherwise has impaired wound healing. If a patient presents with systemic symptoms, they should be referred to an emergency care facility for further management.

Final Thoughts

Sea urchin injuries can lead to serious complications if not diagnosed quickly and treated properly. Retention of sea urchin spines in the deep tissues and joint spaces may lead to granulomas, inflammatory and infectious tenosynovitis (including mycobacterial infection), and sea urchin arthritis requiring surgical debridement and possible irreversible joint damage, up to a year after initial injury. Patients should be educated on the possibility of developing these delayed reactions and instructed to seek immediate care. Joint deformities, range-of-motion deficits, and involvement of neurovascular structures should be considered emergent and referred for proper management. Shoes and diving gear offer some protection but are easily penetrable by sharp sea urchin spines. Preventive focus should be aimed at educating patients and providers on the importance of prompt spine removal upon injury. Although dermatologic and systemic manifestations vary widely, a thorough history, physical examination, and appropriate use of imaging modalities can facilitate accurate diagnosis and guide treatment.