Federal Practitioner

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

Patients with moderate to severe osteoarthritis (OA) or osteonecrosis (ON) eligible for total joint arthroplasty (TJA) who have failed one or more nonoperative therapies should proceed directly to surgery, according to new guidelines from the American College of Rheumatology and the American Association of Hip and Knee Surgeons.

“One of the reasons for creating this guideline was that many patients have been subjected to delays for surgery after completing nonoperative therapy, despite persistent moderate to severe pain, loss of function, and moderate to severe radiographic OA or ON,” said coauthors Susan M. Goodman, MD, a rheumatologist at Hospital for Special Surgery in New York, and Charles Hannon, MD, an orthopedic surgeon at Washington University in St. Louis, in an email interview with this news organization. “This guideline supports surgery being performed in an expeditious fashion after the decision has been made to proceed with surgery by both the physician and patient through a shared decision-making process,” they said.

The guidelines also state that obesity by itself should not be a reason to delay TJA. “We could not find a rationale for a strict cut off for weight/body mass index (BMI). Our literature review revealed that though many adverse events were, in fact, increased in patients with morbid obesity, there is also an increase in adverse events for those who had bariatric surgery prior to their arthroplasty,” they added, noting that patients need to be made aware of the increased risk for adverse events in patients with obesity. Though the guidelines do not pose any BMI cutoffs, they state that weight loss should be “strongly encouraged.” These new recommendations are conditional, and all had a “low” to “very low” certainty of evidence; however, there was high consensus on the recommendations from the expert panel.

The guidelines also recommended:

• Delaying TJA to achieve smoking and nicotine cessation or reduction.
• Delaying TJA to improve glycemic control in patients with diabetes, although the group did not recommend any specific measure or threshold.
• Not delaying TJA in patients with a severe deformity, bone loss, or a neuropathic joint.

The new guidelines formalize what many surgeons have already been doing for the past few years, said Arjun Saxena, MD, MBA, an orthopedic surgeon in Philadelphia who was not involved with the guidelines. “A lot of total joint programs have really focused on patient optimization, including smoking cessation, glycemic control, and weight loss prior to surgery,” he said.

Most importantly, the guidelines put an emphasis on how the decision to proceed with TJA should be a shared decision between a physician and patient, he added. Some insurance companies with prior authorization policies may require a patient to try additional nonoperative therapies before approving surgery, creating barriers to care, he said. “Hopefully [these new recommendations] will help third parties understand that joint replacement is a big decision – most doctors aren’t going to recommend that unless it’s necessary or something that is going to help patients,” he said. “I understand that there is a certain need for preauthorization, but just having strict guidelines isn’t appropriate. You really need to look at the whole picture,” he added.

The full manuscript has been submitted for review and is expected to be jointly published in American College of Rheumatology and the American Association of Hip and Knee Surgeons journals later this year.

Dr. Saxena consults for the orthopedic implant company Corin.

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

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

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

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

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

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

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

NEW ORLEANS – Application of a single-use disposable patch to the axillary area for up to 3 minutes led to statistically significant and clinically meaningful benefit for patients with primary axillary hyperhidrosis, results from a pivotal randomized trial showed.

“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Koldunov/Thinkstock

Adverse events

A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.

Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.

The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”

Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”

The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Application of a single-use disposable patch to the axillary area for up to 3 minutes led to statistically significant and clinically meaningful benefit for patients with primary axillary hyperhidrosis, results from a pivotal randomized trial showed.

“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Koldunov/Thinkstock

Adverse events

A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.

Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.

The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”

Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”

The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Application of a single-use disposable patch to the axillary area for up to 3 minutes led to statistically significant and clinically meaningful benefit for patients with primary axillary hyperhidrosis, results from a pivotal randomized trial showed.

“This is a new kind of device that is going to be a nice tool to have for treating patients who have hyperhidrosis of the axilla,” the study’s lead investigator, David M. Pariser, MD, who practices dermatology in Norfolk, Va., said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Koldunov/Thinkstock

Adverse events

A total of 13 patients in the active patch group experienced AEs at the treatment site, including six with erythema; four with erosion; two with burning, itching or stinging; and one with underarm odor. “The two procedure-related AEs in the TAT-treated group were compensatory sweating and irritant contact dermatitis due to the adhesive,” said Dr. Pariser said.

Most adverse events resolved in fewer than 2 weeks, and all were mild to moderate. No serious adverse events occurred. Only five adverse events occurred in the sham group.

The TAT patch is currently undergoing review by the Food and Drug Administration, and according to Dr. Pariser, no other body sites have been treated with the device.

Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was asked to comment on the study, characterized hyperhidrosis as “an exceedingly common medical condition that is commonly overlooked even though it has a tremendous burden on quality of life. I should know, as both someone who manages a large cohort of these patients but also as someone who suffers from it.”

Treatment options “have historically been limited, many of which are off-label and some which are difficult to access due to cost and/or duration/frequency of treatment,” added Dr. Friedman, who was not involved with the study. “The TAT patch offers a new, targeted, in-office, practical procedure-based approach to treat primary axillary hyperhidrosis. Innovation is certainly welcomed and needed, and I am curious to see how this technology is employed in practice once approved.”

The device is being developed by Candesant Biomedical. Dr. Pariser disclosed that he is a consultant or investigator for Bickel Biotechnology, Biofrontera AG, Bristol Myers Squibb, Celgene Corporation, Novartis Pharmaceuticals, Pfizer, Regeneron, and Sanofi.

Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Assessing underlying mechanisms for the effects of age, mean platelet volume (MPV), and tryptase may help identify pediatric patients with chronic spontaneous urticaria (CSU) who will respond to different treatment options, results from a single-center prospective study showed.

“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.

NEW ORLEANS – Assessing underlying mechanisms for the effects of age, mean platelet volume (MPV), and tryptase may help identify pediatric patients with chronic spontaneous urticaria (CSU) who will respond to different treatment options, results from a single-center prospective study showed.

“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.

NEW ORLEANS – Assessing underlying mechanisms for the effects of age, mean platelet volume (MPV), and tryptase may help identify pediatric patients with chronic spontaneous urticaria (CSU) who will respond to different treatment options, results from a single-center prospective study showed.

“Given that the majority of CSU cases in adults are due to autoimmunity and there being very [few] studies on biomarkers for CSU in children, our study furthers our current understanding of the role of different biomarkers in treatment response,” lead study author Alex Nguyen, MsC, said in an interview at the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

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

Lanolin, known mainly for its emollient properties, has been named by the American Contact Dermatitis Society as the Contact Allergen of the Year for 2023.

Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.

Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.

“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.

“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”

And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.

“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
 

Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.

Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.

Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
 

Consider high-risk groups

Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.

Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.

Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”

Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.

Lanolin, known mainly for its emollient properties, has been named by the American Contact Dermatitis Society as the Contact Allergen of the Year for 2023.

Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.

Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.

“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.

“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”

And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.

“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
 

Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.

Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.

Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
 

Consider high-risk groups

Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.

Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.

Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”

Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.

Lanolin, known mainly for its emollient properties, has been named by the American Contact Dermatitis Society as the Contact Allergen of the Year for 2023.

Lanolin is a complex and varying mixture of high molecular weight esters, aliphatic alcohols, sterols, fatty acids, and hydrocarbons, but the allergic components are mainly the free lanolin alcohols, especially alkanediols, said Donald V. Belsito, MD, professor of dermatology, Columbia University, New York, who announced the Allergen of the Year at the society’s annual meeting.

Criteria for selection can include a known allergen with a new twist or increasing frequency or a newly reported allergen with mini-epidemics that may have been missed for years, Dr. Belsito said.

“The prevalence and severity of allergy to ‘lanolin’ have been hotly debated” since a potential case was first reported in the 1920s, wrote Dr. Belsito and Blair A. Jenkins, MD, PhD, a dermatology resident at New York–Presbyterian Hospital, Columbia Campus, in a review published in Dermatitis.

“ ‘Lanolin’ is indeed a paradox allergen,” wrote Dr. Jenkins and Dr. Belsito. “The most appropriate patch test preparation(s) for detecting allergy remain disputed. Detection of lanolin-induced contact dermatitis in diseased skin by patch testing on normal skin may lead to false negative results.”

And those who test positive for a lanolin allergy on diseased skin may be able to use lanolin products on normal skin, they wrote.

“From my perspective, this was a timely year to think about lanolin, as there is significant ongoing controversy about whether it is allergenic,” Dr. Jenkins said in an interview. “Numerous companies market lanolin-containing topicals as safe and effective emollients,” she said.
 

Medical grade and highly purified anhydrous lanolin, which contain less than 2.5% and less than 1.5% of free alcohols, respectively, can still elicit or induce a contact allergy, Dr. Belsito said in his presentation. Hydrogenated lanolin has shown more allergenicity than lanolin alcohol, while lanolin wax, lanolin acid, and lanolin esters possess lower allergenicity than lanolin alcohol, he said.

Notably, modern wool textiles do not contain lanolin, and lanolin-allergic patients need not avoid wool, Dr. Belsito added.

Amerchol L-101, a common trade name on products containing lanolin, contains 10% wool wax alcohols obtained from the hydrolysis of wool fat dissolved in mineral oil at a 1:1 ratio, said Dr. Belsito. He recommended testing lanolin alcohols (in 30% petrolatum) and Amerchol L-101 (in 50% petrolatum) simultaneously with or without other lanolin derivatives and/or the patient’s products in cases of possible allergy, he said.
 

Consider high-risk groups

Current evidence suggests that the prevalence of contact allergy in the western European population is 0.4%, wrote Dr. Jenkins and Dr. Belsito.

Although the frequency of lanolin allergy is relatively low, certain conditions convey greater risk, such as stasis dermatitis, leg ulcers, perianal/genital dermatitis, and atopic dermatitis, they wrote. Older adults and children are at increased risk because they are more likely to have these conditions. Demographic data also suggest that lanolin allergy is more common in non-Hispanic Whites than in non-Hispanic Blacks, they wrote.

Looking ahead, “I think further exploration of allergy across different skin types and ethnicities is warranted,” Dr. Jenkins said. “Further investigation of ideal [lanolin] allergens for patch testing is also needed.”

Dr. Jenkins and Dr. Belsito said they had no relevant financial conflicts to disclose.

NEW ORLEANS – Among the 10 most viewed YouTube videos regarding topical steroid withdrawal, patient testimonials had the poorest quality and reliability of all information sources, results from a novel analysis showed.

“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”

Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.

Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”

The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.

“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.

Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.

Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”

One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”

Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.

NEW ORLEANS – Among the 10 most viewed YouTube videos regarding topical steroid withdrawal, patient testimonials had the poorest quality and reliability of all information sources, results from a novel analysis showed.

“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”

Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.

Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”

The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.

“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.

Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.

Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”

One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”

Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.

NEW ORLEANS – Among the 10 most viewed YouTube videos regarding topical steroid withdrawal, patient testimonials had the poorest quality and reliability of all information sources, results from a novel analysis showed.

“Video-sharing platforms such as YouTube are a great place for patients to connect and find community with others dealing with the same conditions,” senior author Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. “There is no doubt tremendous value in viewing the shared experience; however, it is important that medical advice be evidence based and validated. Seeking said advice from a medical professional such as a board-certified dermatologist will no doubt increase the likelihood that said guidance is supported by the literature and most importantly, will do no harm.”

Noting a trend of increased user-created content on social media and Internet sites about topical steroid withdrawal in recent years, Dr. Friedman, first author Erika McCormick, a fourth-year medical student at George Washington University, and colleagues used the keywords “topical steroid withdrawal” on YouTube to search for and analyze the top 10 most viewed videos on the subject.

Two independent reviewers used the modified DISCERN (mDISCERN) tool and the Global Quality Scale (GQS) to assess reliability and quality/scientific accuracy of videos, respectively. Average scores were generated for each video and the researchers used one way ANOVA, unpaired t-tests, and linear regression to analyze the ratings. For mDISCERN criteria, a point is given per each of five criteria for a possible score between 0 and 5. Examples of criteria included “Are the aims clear and achieved?” and “Is the information presented both balanced and unbiased”? For GQS, a score from 1 to 5 is designated based on criteria ranging from “poor quality, poor flow, most information missing” to “excellent quality and flow, very useful for patients.”

The researchers found that the mean combined mDISCERN score of the 10 videos was a 2, which indicates poor reliability and shortcomings. Similarly, the combined mean GQS score was 2.5, which suggests poor to moderate quality of videos, missing discussion of important topics, and limited use to patients. The researchers found no correlation between mDISCERN or GQS scores and length of video, duration on YouTube, or number of views, subscribers, or likes.

“We were disheartened that patient testimonial videos had the poorest quality and reliability of the information sources,” Ms. McCormick said in an interview. “Videos that included medical research and information from dermatologists had significantly higher quality and reliability scores than the remainder of videos.” Accurate information online is essential to help patients recognize topical steroid withdrawal and seek medical care, she continued.

Conversely, wide viewership of unreliable information “may contribute to fear of topical corticosteroids and dissuade use in patients with primary skin diseases that may benefit from this common treatment,” Dr. Friedman said. “Dermatologists must be aware of the content patients are consuming online, should guide patients in appraising quality and reliability of online resources, and must provide valid sources of additional information for their patients.” One such resource he recommended is the National Eczema Association, which has created online content for patients about topical steroid withdrawal.

Doris Day, MD, a New York–based dermatologist who was asked to comment on the study, said that many patients rely on YouTube as a go-to resource, with videos that can be watched at times of their choosing. “Oftentimes, the person on the video is relatable and has some general knowledge but is lacking the information that would be relevant and important for the individual patient,” said Dr. Day, who was not involved with the study. “The downside of this is that the person who takes that advice may not use the prescription properly or for the correct amount of time, which can lead to either undertreating or, even worse, overtreatment, which can have permanent consequences.”

One possible solution is for more doctors to create videos for YouTube, she added, “but that doesn’t guarantee that those would be the ones patients would choose to watch.” Another solution “is to have YouTube add qualifiers indicating that the information being discussed is not medical,” she suggested. “Ideally, patients will get all the information they need while they are in the office and also have clear written instructions and even a video they can review at a later time, made by the office, to help them feel they are getting personalized care and the attention they need.”

Ms. McCormick’s research is funded by a grant from Galderma. Dr. Friedman and Dr. Day had no relevant disclosures to report.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

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

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

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

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

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

As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, Ky., spends his working hours in casinos, covering a large territory including Norfolk, Va., Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic.

There was one nervous night when his temperature rose to 101° F, and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared, and he was back to normal soon. “Maybe it was just an exhausting day.”

Mr. Alexander is one of those people who have managed – or at least think they have managed – to avoid getting COVID-19.

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck. On Twitter, NOVIDs share stories of how they’ve done it.