A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

A panel of advisers to the Food and Drug Administration has recommended against approval of omecamtiv mecarbil (Cytokinetics) for the treatment of heart failure with reduced ejection fraction (HFrEF).

Omecamtiv mecarbil is a first-in-class, selective cardiac myosin activator designed to improve cardiac performance.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The FDA Cardiovascular and Renal Drugs Advisory Committee on Dec. 13 voted 8 to 3 (with no abstentions) that the benefits of omecamtiv mecarbil do not outweigh the risks for HFrEF.

Those who voted in favor of the drug cited the clinical benefit (albeit small) and good safety profile of the drug as well as the unmet need for new treatments.

C. Noel Bairey Merz, MD, Cedars-Sinai Medical Center, Los Angeles, said she voted yes “on the basis of need,” and her personal experience, as well as the data presented, that “up to half of severe heart failure patients are intolerant of guidelines directed medical therapy.”

Christopher M. O’Connor, MD, with Inova Heart and Vascular Institute, Falls Church, Va., who also voted in favor of approval for the drug, cited the “important unmet need,” and said he believes “a path was constructed in which one could go forward safely and with enhanced efficacy.

“It may be a narrow path, but I think it’s a path that would afford a lot of benefit to this high-risk patient population,” said Dr. O’Connor.

Those who voted against approval generally felt the benefit was not large enough and that more data are needed, given this is a first-in-class agent.

Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who voted no, said she was concerned that, despite the large size of the trial, “a more positive effect could not have been found.” She was also concerned that there was no benefit on quality of life or any other secondary outcomes. 

David J. Moliterno, MD, University of Kentucky Medical Center, Lexington, who also voted no, felt the benefits were “more singular and that being a modest reduction primarily limited to fewer outpatient visits.” Dr. Moliterno, like many of the committee members who voted no, called for more study.

The committee’s decision was based on results from the phase 3 GALACTIC-HF trial, which enrolled 8,256 patients with HFrEF who were at risk of hospitalization and death, despite standard-of-care therapy.

As previously reported by this news organization, omecamtiv mecarbil produced a positive result for the study’s primary endpoint, with a 2.1% absolute reduction in the combined rate of cardiovascular (CV) death, first HF hospitalization, or first urgent visit for HF, compared with placebo during a median follow-up of about 22 months.

This represented an 8% relative risk reduction and broke down as a 0.6% absolute drop in CV death, compared with placebo, a 0.7% cut in HF hospitalization, and a 0.8% drop in urgent outpatient HF visits.

The results were presented at the American Heart Association 2020 scientific sessions and simultaneously published in the New England Journal of Medicine.

In a statement, Robert I. Blum, president and CEO of Cytokinetics, said, “We are disappointed there was not a greater consensus amongst committee members relating to the benefit-risk of omecamtiv mecarbil, and we maintain our conviction in the strength of evidence supporting its potential benefit for patients suffering from HFrEF.”

He added that the company plans to engage constructively with the FDA as it completes its review of the application for omecamtiv mecarbil. 

The drug has a Prescription Drug User Fee Act target date of Feb. 28, 2023.

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

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Maybe the cow was late for its appointment

It’s been a long day running the front desk at your doctor’s office. People calling in prescriptions, a million appointments, you’ve been running yourself ragged keeping things together. Finally, it’s almost closing time. The last patient of the day has just checked out and you turn back to the waiting room, expecting to see it blessedly empty.

Instead, a 650-pound cow is staring at you.

“I’m sorry, sir or madam, we’re about to close.”

Moo.
 

tilo/Thinkstock

We can see that decision in your eyes

The cliché that eyes are the windows to the soul doesn’t tell the whole story about how telling eyes really are. It’s all about how they move. In a recent study, researchers determined that a type of eye movement known as a saccade reveals your choice before you even decide.

pxfuel

Saccades involve the eyes jumping from one fixation point to another, senior author Alaa Ahmed of the University of Colorado, Boulder, explained in a statement from the university. Saccade vigor was the key in how aligned the type of decisions were made by the 22 study participants.

In the study, subjects walked on a treadmill at varied inclines for a period of time. Then they sat in front of a monitor and a high-speed camera that tracked their eye movements as the monitor presented them with a series of exercise options. The participants had only 4 seconds to choose between them.

After they made their choices, participants went back on the treadmill to perform the exercises they had chosen. The researchers found that participants’ eyes jumped between the options slowly then faster to the option they eventually picked. The more impulsive decision-makers also tended to move their eyes even more rapidly before slowing down after a decision was made, making it pretty conclusive that the eyes were revealing their choices.

The way your eyes shift gives you away without saying a thing. Might be wise, then, to wear sunglasses to your next poker tournament.
 

Let them eat soap

Okay, we admit it: LOTME spends a lot of time in the bathroom. Today, though, we’re interested in the sinks. Specifically, the P-traps under the sinks. You know, the curvy bit that keeps sewer gas from wafting back into the room?

PxHere

Well, researchers from the University of Reading (England) recently found some fungi while examining a bunch of sinks on the university’s Whiteknights campus. “It isn’t a big surprise to find fungi in a warm, wet environment. But sinks and P-traps have thus far been overlooked as potential reservoirs of these microorganisms,” they said in a written statement.

Samples collected from 289 P-traps contained “a very similar community of yeasts and molds, showing that sinks in use in public environments share a role as reservoirs of fungal organisms,” they noted.

The fungi living in the traps survived conditions with high temperatures, low pH, and little in the way of nutrients. So what were they eating? Some varieties, they said, “use detergents, found in soap, as a source of carbon-rich food.” We’ll repeat that last part: They used the soap as food.

WARNING: Rant Ahead.

There are a lot of cleaning products for sale that say they will make your home safe by killing 99.9% of germs and bacteria. Not fungi, exactly, but we’re still talking microorganisms. Molds, bacteria, and viruses are all stuff that can infect humans and make them sick.

So you kill 99.9% of them. Great, but that leaves 0.1% that you just made angry. And what do they do next? They learn to eat soap. Then University of Reading investigators find out that all the extra hand washing going on during the COVID-19 pandemic was “clogging up sinks with nasty disease-causing bacteria.”

These are microorganisms we’re talking about people. They’ve been at this for a billion years! Rats can’t beat them, cockroaches won’t stop them – Earth’s ultimate survivors are powerless against the invisible horde.

We’re doomed.

Exposure to inhaled agents in the workplace could be putting people at risk of developing rheumatoid arthritis, according to research published in Annals of the Rheumatic Diseases.

In an analysis of data from the long-running Swedish Epidemiological Investigation of RA (EIRA) population-based cohort study, there was a 21% increased risk of RA and a 25% increased risk of anti–citrullinated protein antibody (ACPA)–positive RA associated with exposure to any occupationally inhaled agent.

LOOK PHOTO / Fotolia.com

“We have investigated a number of occupational airborne exposures and found that exposure for those agents infer a high risk for RA,” Lars Klareskog, MD, PhD, senior professor of rheumatology at the Karolinska Institute and Karolinska University Hospital (Solna) in Stockholm, said in an interview.

Dr. Klareskog, who is one of the lead authors of the published work, added that the risk is particularly high in individuals who had a genetic susceptibility and in those who smoked.

“The importance of this is that it further demonstrates that exposures to the lung may trigger immune reactions associated with the major subset of rheumatoid arthritis,” Dr. Klareskog said. “Second, it shows that those exposed to these agents should be very keen to not smoke.” “These findings further implicate the respiratory tract mucosa in ACPA-positive RA pathogenesis,” agreed Vanessa L. Kronzer, MD, of the Mayo Clinic in Rochester, Minn., and Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

They also “impress the need for public policy initiatives related to occupational inhalants to prevent RA,” they suggested in an editorial.

Multiple occupational inhalable exposures assessed

In the analysis, the researchers assessed exposure to 32 inhalable agents in people with (n = 4,033) and without RA (n = 6,485). The list of agents considered included detergents, diesel engine exhaust, fine particulate matter, solvents, and agricultural chemicals.

A total of 17 agents showed a positive association with an increased risk of ACPA-positive RA. Dr. Kronzer and Dr. Sparks noted that breathing in insecticides and fungicides at work was associated with the highest odds ratios for having ACPA-positive RA (both 2.38).

“Importantly, both the number and duration of exposures exhibited a dose-response effect on RA risk,” the editorialists said.

They also picked out that there was “a gene-environment interaction for RA risk for certain inhalants,” including diesel engine exhaust, asbestos, carbon monoxide, and quartz dust.

Smoking amplified the risk for ACPA-positive RA associated with certain agents, such as detergents, and adding in genetic susceptibility for a third exposure increased the risk still further.

A key message is that there are many agents that can affect the airways and increase the risk of RA rather than there being a specific one, Dr. Klareskog said.

“On one hand, it’s a message of public health,” he said. Many public health authorities are aware of the potential risks of inhaled agents on the lung, “but this just adds another dimension that it’s bad also for rheumatoid arthritis.” Thus, greater efforts to help protect people from being exposed at work may be needed.

From the individual’s perspective, “if you have RA or other immune diseases in your family, then you may know that you’re at increased risk,” Dr. Klareskog said. The message here is perhaps to “be aware, [protect yourself], and stop smoking.”

The EIRA study was supported by funding from the Swedish Research Foundation for Health, Working Life, and Welfare, the Swedish Research Council, the AFA foundation, Region Stockholm, King Gustaf V’s 80-year foundation, and the Swedish Rheumatic Foundation. Dr. Klareskog and coauthors had no competing interests to disclose. Dr. Kronzer and Dr. Sparks had no disclosures of relevance to their comments.

Exposure to inhaled agents in the workplace could be putting people at risk of developing rheumatoid arthritis, according to research published in Annals of the Rheumatic Diseases.

In an analysis of data from the long-running Swedish Epidemiological Investigation of RA (EIRA) population-based cohort study, there was a 21% increased risk of RA and a 25% increased risk of anti–citrullinated protein antibody (ACPA)–positive RA associated with exposure to any occupationally inhaled agent.

LOOK PHOTO / Fotolia.com

“We have investigated a number of occupational airborne exposures and found that exposure for those agents infer a high risk for RA,” Lars Klareskog, MD, PhD, senior professor of rheumatology at the Karolinska Institute and Karolinska University Hospital (Solna) in Stockholm, said in an interview.

Dr. Klareskog, who is one of the lead authors of the published work, added that the risk is particularly high in individuals who had a genetic susceptibility and in those who smoked.

“The importance of this is that it further demonstrates that exposures to the lung may trigger immune reactions associated with the major subset of rheumatoid arthritis,” Dr. Klareskog said. “Second, it shows that those exposed to these agents should be very keen to not smoke.” “These findings further implicate the respiratory tract mucosa in ACPA-positive RA pathogenesis,” agreed Vanessa L. Kronzer, MD, of the Mayo Clinic in Rochester, Minn., and Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

They also “impress the need for public policy initiatives related to occupational inhalants to prevent RA,” they suggested in an editorial.

Multiple occupational inhalable exposures assessed

In the analysis, the researchers assessed exposure to 32 inhalable agents in people with (n = 4,033) and without RA (n = 6,485). The list of agents considered included detergents, diesel engine exhaust, fine particulate matter, solvents, and agricultural chemicals.

A total of 17 agents showed a positive association with an increased risk of ACPA-positive RA. Dr. Kronzer and Dr. Sparks noted that breathing in insecticides and fungicides at work was associated with the highest odds ratios for having ACPA-positive RA (both 2.38).

“Importantly, both the number and duration of exposures exhibited a dose-response effect on RA risk,” the editorialists said.

They also picked out that there was “a gene-environment interaction for RA risk for certain inhalants,” including diesel engine exhaust, asbestos, carbon monoxide, and quartz dust.

Smoking amplified the risk for ACPA-positive RA associated with certain agents, such as detergents, and adding in genetic susceptibility for a third exposure increased the risk still further.

A key message is that there are many agents that can affect the airways and increase the risk of RA rather than there being a specific one, Dr. Klareskog said.

“On one hand, it’s a message of public health,” he said. Many public health authorities are aware of the potential risks of inhaled agents on the lung, “but this just adds another dimension that it’s bad also for rheumatoid arthritis.” Thus, greater efforts to help protect people from being exposed at work may be needed.

From the individual’s perspective, “if you have RA or other immune diseases in your family, then you may know that you’re at increased risk,” Dr. Klareskog said. The message here is perhaps to “be aware, [protect yourself], and stop smoking.”

The EIRA study was supported by funding from the Swedish Research Foundation for Health, Working Life, and Welfare, the Swedish Research Council, the AFA foundation, Region Stockholm, King Gustaf V’s 80-year foundation, and the Swedish Rheumatic Foundation. Dr. Klareskog and coauthors had no competing interests to disclose. Dr. Kronzer and Dr. Sparks had no disclosures of relevance to their comments.

Exposure to inhaled agents in the workplace could be putting people at risk of developing rheumatoid arthritis, according to research published in Annals of the Rheumatic Diseases.

In an analysis of data from the long-running Swedish Epidemiological Investigation of RA (EIRA) population-based cohort study, there was a 21% increased risk of RA and a 25% increased risk of anti–citrullinated protein antibody (ACPA)–positive RA associated with exposure to any occupationally inhaled agent.

LOOK PHOTO / Fotolia.com

“We have investigated a number of occupational airborne exposures and found that exposure for those agents infer a high risk for RA,” Lars Klareskog, MD, PhD, senior professor of rheumatology at the Karolinska Institute and Karolinska University Hospital (Solna) in Stockholm, said in an interview.

Dr. Klareskog, who is one of the lead authors of the published work, added that the risk is particularly high in individuals who had a genetic susceptibility and in those who smoked.

“The importance of this is that it further demonstrates that exposures to the lung may trigger immune reactions associated with the major subset of rheumatoid arthritis,” Dr. Klareskog said. “Second, it shows that those exposed to these agents should be very keen to not smoke.” “These findings further implicate the respiratory tract mucosa in ACPA-positive RA pathogenesis,” agreed Vanessa L. Kronzer, MD, of the Mayo Clinic in Rochester, Minn., and Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston.

They also “impress the need for public policy initiatives related to occupational inhalants to prevent RA,” they suggested in an editorial.

Multiple occupational inhalable exposures assessed

In the analysis, the researchers assessed exposure to 32 inhalable agents in people with (n = 4,033) and without RA (n = 6,485). The list of agents considered included detergents, diesel engine exhaust, fine particulate matter, solvents, and agricultural chemicals.

A total of 17 agents showed a positive association with an increased risk of ACPA-positive RA. Dr. Kronzer and Dr. Sparks noted that breathing in insecticides and fungicides at work was associated with the highest odds ratios for having ACPA-positive RA (both 2.38).

“Importantly, both the number and duration of exposures exhibited a dose-response effect on RA risk,” the editorialists said.

They also picked out that there was “a gene-environment interaction for RA risk for certain inhalants,” including diesel engine exhaust, asbestos, carbon monoxide, and quartz dust.

Smoking amplified the risk for ACPA-positive RA associated with certain agents, such as detergents, and adding in genetic susceptibility for a third exposure increased the risk still further.

A key message is that there are many agents that can affect the airways and increase the risk of RA rather than there being a specific one, Dr. Klareskog said.

“On one hand, it’s a message of public health,” he said. Many public health authorities are aware of the potential risks of inhaled agents on the lung, “but this just adds another dimension that it’s bad also for rheumatoid arthritis.” Thus, greater efforts to help protect people from being exposed at work may be needed.

From the individual’s perspective, “if you have RA or other immune diseases in your family, then you may know that you’re at increased risk,” Dr. Klareskog said. The message here is perhaps to “be aware, [protect yourself], and stop smoking.”

The EIRA study was supported by funding from the Swedish Research Foundation for Health, Working Life, and Welfare, the Swedish Research Council, the AFA foundation, Region Stockholm, King Gustaf V’s 80-year foundation, and the Swedish Rheumatic Foundation. Dr. Klareskog and coauthors had no competing interests to disclose. Dr. Kronzer and Dr. Sparks had no disclosures of relevance to their comments.

Sir Augustus d’Este (1794-1848) described the circumstances preceding his development of neurological symptoms as follows:¹ “I travelled from Ramsgate to the Highlands of Scotland for the purpose of passing some days with a Relation for whom I had the affection of a Son. On my arrival I found him dead. Shortly after the funeral I was obliged to have my letters read to me, and their answers written for me, as my eyes were so attacked that when fixed upon minute objects indistinctness of vision was the consequence: Soon after I went to Ireland, and without any thing having been done to my eyes, they completely recovered their strength and distinctness of vision…" He then described a clinical course of relapsing-remitting neurologic symptoms merging into a progressive stage of unrelenting illness, most fitting with what we know today as multiple sclerosis (MS).¹ Why did Sir Augustus d'Este connect the event of the unexpected death to the onset of a lifelong neurologic disease?

Jean-Martin Charcot first described MS in a way close to what we know it as today. Charcot considered stress a factor in MS. He linked grief, vexation, and adverse changes in social circumstances to the onset of MS at that time.² I, as a practicing MS specialist, am surprised neither by Sir Augustus d'Este's diary nor by Charcot's earlier assessments of MS triggers.³ As I write this narrative, I think of the many times I heard from people diagnosed with MS. "It happened to me because of stress" is a statement not estranged from my daily clinical practice

MS as a multifactorial disease

It is tempting to make a case for emotional stress as a cause of MS, but one must remember that MS is a very complex disease with unclear etiologies. MS, a treatable but not yet curable disease, is the interplay between the genetics of the host and numerous environmental factors that exploit a susceptible immune system leading to unrelenting immune dysregulation.⁴ Recent studies have brought some pieces of this intricate puzzle together. The role of Epstein-Barr virus (EBV) in the pathogenesis of MS is being dissected.⁵ The possible synergy between vitamin D deficiency, EBV, and certain genetic variations is being studied.⁶ The roles of smoking, environmental toxins, obesity, diet, Western lifestyle, and the gut microbiome are some of the top areas of clinical, translational, and basic research.^7-11 But what about emotional stress? Where does it fit, if anywhere, in the current research paradigm?

Emotional stress and MS—Causality or not?

In the scientific method, several criteria must be proven for an element to be suspected in the etiology of a disease.¹² First, the suspect element must be present before the disease starts—i.e., a temporal association. Second, there must be a plausible biological explanation of how the suspect element acts in the disease's causation. Third, other variables that could confound the picture must be controlled for or dismissed. It is clear that no single factor is the cause of MS. By now, MS is agreed upon as a disease caused by multiple factors, some of which remain to be unraveled.⁹ The term "cause" has been utilized more recently by many authors when referring to EBV in relation to MS development, reasoning that in one study, in a small number of individuals with MS, EBV infection preceded the MS clinical diagnosis.¹³ Thus, the temporal association was provided. But does MS start at the onset of clinical symptoms?

For Sir Augustus d'Este, the disease may have started years before he visited the Highlands of Scotland, but only at that visit did MS become clinically apparent. So, the emotional trauma may have acted as a "trigger" for an MS flare-up rather than being a "cause" of MS. This might be a more plausible explanation of the association between emotional trauma and MS development. However, MS pathogenesis is complex, and one could argue that the disease starts many years before the first clinical symptoms that lead to diagnosis.

The MS prodrome has been demonstrated by several studies that suggest that MS may start many years before the clinical diagnosis.¹⁴ Radiologically isolated syndrome (RIS) further argues that MS may be clinically dormant for years, and clinical symptoms may not appear until later in the disease process.¹⁵ One may think that immune attacks on the optic nerves, spinal cord, or areas of the brainstem might be readily symptomatic compared to attacks on other structures of the central nervous system (e.g., periventricular or juxtacortical brain areas) that may be clinically silent. So, while for Sir Augustus d'Este it seemed that the disease started at the time of his visit to the Highlands of Scotland, it is equally plausible that it started years before the first clinical attack. Nevertheless, how could emotional stress play a role in the pathophysiology of MS?

Stress and the Immune System

At times of chronic stress, one may become more susceptible to infections. Reactivation of certain viruses can lead to oral ulcers, increased common cold symptoms, or other illnesses. For example, stress can reactivate herpes simplex type 1 and interestingly, EBV.^16,17 In MS, the immune system is dysregulated and has an autoimmune component. The effect of acute emotional stress differs from that of chronic stress.¹⁸ Several studies have examined the immune responses to both forms of stress.^19-21

Interestingly, acute stress activates cell-mediated immunity, increases immune cell trafficking to areas of injury, and, importantly, increases blood-brain barrier (BBB) permeability by activating resident mast cells in the brain and other areas, including the optic nerves.^22,23 Mast cell activation leads to BBB disruption, which is a key early step in the pathogenesis of MS. Thus, it is plausible that the proinflammatory changes associated with acute stress could be implicated in the pathogenesis of MS. This contrasts with chronic stress, which attenuates various immune responses, including suppressing cell-mediated immunity, but also dysregulate the immune system.

One could establish a biological plausibility for stress playing a role in the proinflammatory responses in MS. Whether it is causal or not, scientists can further explore the potential biologic explanations. While studying the association between acute stress and MS development or disease activity is difficult, several groups have examined the potential association. Many studies, however, have limitations due to the difficult nature of studying such an association, especially in quantifying or defining acute stress in general.

A limited number of studies on MS and stress: What do we know? And what are the challenges?

Rare studies have reported a potential association between MS development and stressful life events, while others reported no association.^24-26 Also, some studies observed an increase in MS relapses or the development of new magnetic resonance imaging (MRI) lesions following stressful life events or wartime, while others failed to show such an association.^26-30 There are few studies directly addressing the potential association between acute emotional stress and MS. The results of published studies are variable, and limitations are numerous. Limitations include the difficulty in measuring acute emotional stress, difficulty in its prediction, and ethical challenges of experimental design and recruiting participants. So, studies have focused on observational aspects, retrospective reviews, and surveys of memories prone to various biases. Rarely was the design of these clinical studies prospective. A few prospective studies reported an association between stressful life events and increased MS relapses and increased number of brain lesions.^27,31,32 Rare clinical trials have attempted to test stress reduction strategies and reported on the modest improvement of patient-reported outcomes and, in one study, a modest improvement in new MRI lesions.^33-35

Overall, several lines of evidence support a potential association between acute emotional stress and MS. Yet, the association is challenging to study, and future research might focus on stress-mitigation strategies and improving coping mechanisms in persons living with MS. It is important to note that it will be very difficult to design prospective studies to examine the potential association between acute emotional trauma and the development of de novo MS. Such studies will require a large number of participants (e.g., hundreds of thousands), long durations of follow-up (e.g., decades), and ways to classify repeated stressful events. An alternative approach is to ask persons newly diagnosed with MS at the time of initial diagnosis about any temporal association between their first symptom and stressful life events. However, this approach would provide some information on any association between the two, but not on causality of the disease itself.

Conclusion

The potential association between acute emotional stress and MS dates to the times of early descriptions of MS. Yet, research has been very limited and challenging. To date, the potential association remains elusive. Lines of evidence, while with limitations, have provided possible biologic explanations for the relationship between MS symptom onset and acute emotional stress. Although avoiding acute emotional stress is nearly impossible, incorporating global stress-coping strategies in early childhood education and secondary education might theoretically have potential beneficial effects on the subsequent risk of MS development or symptom flare-up, depending on a variety of factors.

But for now, when patients and colleagues ask me, “Can acute emotional stress be a ‘trigger’ for MS symptomology?,” my answer will remain, “Potentially, until proven otherwise.”

Sir Augustus d’Este (1794-1848) described the circumstances preceding his development of neurological symptoms as follows:¹ “I travelled from Ramsgate to the Highlands of Scotland for the purpose of passing some days with a Relation for whom I had the affection of a Son. On my arrival I found him dead. Shortly after the funeral I was obliged to have my letters read to me, and their answers written for me, as my eyes were so attacked that when fixed upon minute objects indistinctness of vision was the consequence: Soon after I went to Ireland, and without any thing having been done to my eyes, they completely recovered their strength and distinctness of vision…" He then described a clinical course of relapsing-remitting neurologic symptoms merging into a progressive stage of unrelenting illness, most fitting with what we know today as multiple sclerosis (MS).¹ Why did Sir Augustus d'Este connect the event of the unexpected death to the onset of a lifelong neurologic disease?

Jean-Martin Charcot first described MS in a way close to what we know it as today. Charcot considered stress a factor in MS. He linked grief, vexation, and adverse changes in social circumstances to the onset of MS at that time.² I, as a practicing MS specialist, am surprised neither by Sir Augustus d'Este's diary nor by Charcot's earlier assessments of MS triggers.³ As I write this narrative, I think of the many times I heard from people diagnosed with MS. "It happened to me because of stress" is a statement not estranged from my daily clinical practice

MS as a multifactorial disease

It is tempting to make a case for emotional stress as a cause of MS, but one must remember that MS is a very complex disease with unclear etiologies. MS, a treatable but not yet curable disease, is the interplay between the genetics of the host and numerous environmental factors that exploit a susceptible immune system leading to unrelenting immune dysregulation.⁴ Recent studies have brought some pieces of this intricate puzzle together. The role of Epstein-Barr virus (EBV) in the pathogenesis of MS is being dissected.⁵ The possible synergy between vitamin D deficiency, EBV, and certain genetic variations is being studied.⁶ The roles of smoking, environmental toxins, obesity, diet, Western lifestyle, and the gut microbiome are some of the top areas of clinical, translational, and basic research.^7-11 But what about emotional stress? Where does it fit, if anywhere, in the current research paradigm?

Emotional stress and MS—Causality or not?

In the scientific method, several criteria must be proven for an element to be suspected in the etiology of a disease.¹² First, the suspect element must be present before the disease starts—i.e., a temporal association. Second, there must be a plausible biological explanation of how the suspect element acts in the disease's causation. Third, other variables that could confound the picture must be controlled for or dismissed. It is clear that no single factor is the cause of MS. By now, MS is agreed upon as a disease caused by multiple factors, some of which remain to be unraveled.⁹ The term "cause" has been utilized more recently by many authors when referring to EBV in relation to MS development, reasoning that in one study, in a small number of individuals with MS, EBV infection preceded the MS clinical diagnosis.¹³ Thus, the temporal association was provided. But does MS start at the onset of clinical symptoms?

For Sir Augustus d'Este, the disease may have started years before he visited the Highlands of Scotland, but only at that visit did MS become clinically apparent. So, the emotional trauma may have acted as a "trigger" for an MS flare-up rather than being a "cause" of MS. This might be a more plausible explanation of the association between emotional trauma and MS development. However, MS pathogenesis is complex, and one could argue that the disease starts many years before the first clinical symptoms that lead to diagnosis.

The MS prodrome has been demonstrated by several studies that suggest that MS may start many years before the clinical diagnosis.¹⁴ Radiologically isolated syndrome (RIS) further argues that MS may be clinically dormant for years, and clinical symptoms may not appear until later in the disease process.¹⁵ One may think that immune attacks on the optic nerves, spinal cord, or areas of the brainstem might be readily symptomatic compared to attacks on other structures of the central nervous system (e.g., periventricular or juxtacortical brain areas) that may be clinically silent. So, while for Sir Augustus d'Este it seemed that the disease started at the time of his visit to the Highlands of Scotland, it is equally plausible that it started years before the first clinical attack. Nevertheless, how could emotional stress play a role in the pathophysiology of MS?

Stress and the Immune System

At times of chronic stress, one may become more susceptible to infections. Reactivation of certain viruses can lead to oral ulcers, increased common cold symptoms, or other illnesses. For example, stress can reactivate herpes simplex type 1 and interestingly, EBV.^16,17 In MS, the immune system is dysregulated and has an autoimmune component. The effect of acute emotional stress differs from that of chronic stress.¹⁸ Several studies have examined the immune responses to both forms of stress.^19-21

Interestingly, acute stress activates cell-mediated immunity, increases immune cell trafficking to areas of injury, and, importantly, increases blood-brain barrier (BBB) permeability by activating resident mast cells in the brain and other areas, including the optic nerves.^22,23 Mast cell activation leads to BBB disruption, which is a key early step in the pathogenesis of MS. Thus, it is plausible that the proinflammatory changes associated with acute stress could be implicated in the pathogenesis of MS. This contrasts with chronic stress, which attenuates various immune responses, including suppressing cell-mediated immunity, but also dysregulate the immune system.

One could establish a biological plausibility for stress playing a role in the proinflammatory responses in MS. Whether it is causal or not, scientists can further explore the potential biologic explanations. While studying the association between acute stress and MS development or disease activity is difficult, several groups have examined the potential association. Many studies, however, have limitations due to the difficult nature of studying such an association, especially in quantifying or defining acute stress in general.

A limited number of studies on MS and stress: What do we know? And what are the challenges?

Rare studies have reported a potential association between MS development and stressful life events, while others reported no association.^24-26 Also, some studies observed an increase in MS relapses or the development of new magnetic resonance imaging (MRI) lesions following stressful life events or wartime, while others failed to show such an association.^26-30 There are few studies directly addressing the potential association between acute emotional stress and MS. The results of published studies are variable, and limitations are numerous. Limitations include the difficulty in measuring acute emotional stress, difficulty in its prediction, and ethical challenges of experimental design and recruiting participants. So, studies have focused on observational aspects, retrospective reviews, and surveys of memories prone to various biases. Rarely was the design of these clinical studies prospective. A few prospective studies reported an association between stressful life events and increased MS relapses and increased number of brain lesions.^27,31,32 Rare clinical trials have attempted to test stress reduction strategies and reported on the modest improvement of patient-reported outcomes and, in one study, a modest improvement in new MRI lesions.^33-35

Overall, several lines of evidence support a potential association between acute emotional stress and MS. Yet, the association is challenging to study, and future research might focus on stress-mitigation strategies and improving coping mechanisms in persons living with MS. It is important to note that it will be very difficult to design prospective studies to examine the potential association between acute emotional trauma and the development of de novo MS. Such studies will require a large number of participants (e.g., hundreds of thousands), long durations of follow-up (e.g., decades), and ways to classify repeated stressful events. An alternative approach is to ask persons newly diagnosed with MS at the time of initial diagnosis about any temporal association between their first symptom and stressful life events. However, this approach would provide some information on any association between the two, but not on causality of the disease itself.

Conclusion

The potential association between acute emotional stress and MS dates to the times of early descriptions of MS. Yet, research has been very limited and challenging. To date, the potential association remains elusive. Lines of evidence, while with limitations, have provided possible biologic explanations for the relationship between MS symptom onset and acute emotional stress. Although avoiding acute emotional stress is nearly impossible, incorporating global stress-coping strategies in early childhood education and secondary education might theoretically have potential beneficial effects on the subsequent risk of MS development or symptom flare-up, depending on a variety of factors.

But for now, when patients and colleagues ask me, “Can acute emotional stress be a ‘trigger’ for MS symptomology?,” my answer will remain, “Potentially, until proven otherwise.”

Sir Augustus d’Este (1794-1848) described the circumstances preceding his development of neurological symptoms as follows:¹ “I travelled from Ramsgate to the Highlands of Scotland for the purpose of passing some days with a Relation for whom I had the affection of a Son. On my arrival I found him dead. Shortly after the funeral I was obliged to have my letters read to me, and their answers written for me, as my eyes were so attacked that when fixed upon minute objects indistinctness of vision was the consequence: Soon after I went to Ireland, and without any thing having been done to my eyes, they completely recovered their strength and distinctness of vision…" He then described a clinical course of relapsing-remitting neurologic symptoms merging into a progressive stage of unrelenting illness, most fitting with what we know today as multiple sclerosis (MS).¹ Why did Sir Augustus d'Este connect the event of the unexpected death to the onset of a lifelong neurologic disease?

Jean-Martin Charcot first described MS in a way close to what we know it as today. Charcot considered stress a factor in MS. He linked grief, vexation, and adverse changes in social circumstances to the onset of MS at that time.² I, as a practicing MS specialist, am surprised neither by Sir Augustus d'Este's diary nor by Charcot's earlier assessments of MS triggers.³ As I write this narrative, I think of the many times I heard from people diagnosed with MS. "It happened to me because of stress" is a statement not estranged from my daily clinical practice

MS as a multifactorial disease

It is tempting to make a case for emotional stress as a cause of MS, but one must remember that MS is a very complex disease with unclear etiologies. MS, a treatable but not yet curable disease, is the interplay between the genetics of the host and numerous environmental factors that exploit a susceptible immune system leading to unrelenting immune dysregulation.⁴ Recent studies have brought some pieces of this intricate puzzle together. The role of Epstein-Barr virus (EBV) in the pathogenesis of MS is being dissected.⁵ The possible synergy between vitamin D deficiency, EBV, and certain genetic variations is being studied.⁶ The roles of smoking, environmental toxins, obesity, diet, Western lifestyle, and the gut microbiome are some of the top areas of clinical, translational, and basic research.^7-11 But what about emotional stress? Where does it fit, if anywhere, in the current research paradigm?

Emotional stress and MS—Causality or not?

In the scientific method, several criteria must be proven for an element to be suspected in the etiology of a disease.¹² First, the suspect element must be present before the disease starts—i.e., a temporal association. Second, there must be a plausible biological explanation of how the suspect element acts in the disease's causation. Third, other variables that could confound the picture must be controlled for or dismissed. It is clear that no single factor is the cause of MS. By now, MS is agreed upon as a disease caused by multiple factors, some of which remain to be unraveled.⁹ The term "cause" has been utilized more recently by many authors when referring to EBV in relation to MS development, reasoning that in one study, in a small number of individuals with MS, EBV infection preceded the MS clinical diagnosis.¹³ Thus, the temporal association was provided. But does MS start at the onset of clinical symptoms?

For Sir Augustus d'Este, the disease may have started years before he visited the Highlands of Scotland, but only at that visit did MS become clinically apparent. So, the emotional trauma may have acted as a "trigger" for an MS flare-up rather than being a "cause" of MS. This might be a more plausible explanation of the association between emotional trauma and MS development. However, MS pathogenesis is complex, and one could argue that the disease starts many years before the first clinical symptoms that lead to diagnosis.

The MS prodrome has been demonstrated by several studies that suggest that MS may start many years before the clinical diagnosis.¹⁴ Radiologically isolated syndrome (RIS) further argues that MS may be clinically dormant for years, and clinical symptoms may not appear until later in the disease process.¹⁵ One may think that immune attacks on the optic nerves, spinal cord, or areas of the brainstem might be readily symptomatic compared to attacks on other structures of the central nervous system (e.g., periventricular or juxtacortical brain areas) that may be clinically silent. So, while for Sir Augustus d'Este it seemed that the disease started at the time of his visit to the Highlands of Scotland, it is equally plausible that it started years before the first clinical attack. Nevertheless, how could emotional stress play a role in the pathophysiology of MS?

Stress and the Immune System

At times of chronic stress, one may become more susceptible to infections. Reactivation of certain viruses can lead to oral ulcers, increased common cold symptoms, or other illnesses. For example, stress can reactivate herpes simplex type 1 and interestingly, EBV.^16,17 In MS, the immune system is dysregulated and has an autoimmune component. The effect of acute emotional stress differs from that of chronic stress.¹⁸ Several studies have examined the immune responses to both forms of stress.^19-21

Interestingly, acute stress activates cell-mediated immunity, increases immune cell trafficking to areas of injury, and, importantly, increases blood-brain barrier (BBB) permeability by activating resident mast cells in the brain and other areas, including the optic nerves.^22,23 Mast cell activation leads to BBB disruption, which is a key early step in the pathogenesis of MS. Thus, it is plausible that the proinflammatory changes associated with acute stress could be implicated in the pathogenesis of MS. This contrasts with chronic stress, which attenuates various immune responses, including suppressing cell-mediated immunity, but also dysregulate the immune system.

One could establish a biological plausibility for stress playing a role in the proinflammatory responses in MS. Whether it is causal or not, scientists can further explore the potential biologic explanations. While studying the association between acute stress and MS development or disease activity is difficult, several groups have examined the potential association. Many studies, however, have limitations due to the difficult nature of studying such an association, especially in quantifying or defining acute stress in general.

A limited number of studies on MS and stress: What do we know? And what are the challenges?

Rare studies have reported a potential association between MS development and stressful life events, while others reported no association.^24-26 Also, some studies observed an increase in MS relapses or the development of new magnetic resonance imaging (MRI) lesions following stressful life events or wartime, while others failed to show such an association.^26-30 There are few studies directly addressing the potential association between acute emotional stress and MS. The results of published studies are variable, and limitations are numerous. Limitations include the difficulty in measuring acute emotional stress, difficulty in its prediction, and ethical challenges of experimental design and recruiting participants. So, studies have focused on observational aspects, retrospective reviews, and surveys of memories prone to various biases. Rarely was the design of these clinical studies prospective. A few prospective studies reported an association between stressful life events and increased MS relapses and increased number of brain lesions.^27,31,32 Rare clinical trials have attempted to test stress reduction strategies and reported on the modest improvement of patient-reported outcomes and, in one study, a modest improvement in new MRI lesions.^33-35

Overall, several lines of evidence support a potential association between acute emotional stress and MS. Yet, the association is challenging to study, and future research might focus on stress-mitigation strategies and improving coping mechanisms in persons living with MS. It is important to note that it will be very difficult to design prospective studies to examine the potential association between acute emotional trauma and the development of de novo MS. Such studies will require a large number of participants (e.g., hundreds of thousands), long durations of follow-up (e.g., decades), and ways to classify repeated stressful events. An alternative approach is to ask persons newly diagnosed with MS at the time of initial diagnosis about any temporal association between their first symptom and stressful life events. However, this approach would provide some information on any association between the two, but not on causality of the disease itself.

Conclusion

The potential association between acute emotional stress and MS dates to the times of early descriptions of MS. Yet, research has been very limited and challenging. To date, the potential association remains elusive. Lines of evidence, while with limitations, have provided possible biologic explanations for the relationship between MS symptom onset and acute emotional stress. Although avoiding acute emotional stress is nearly impossible, incorporating global stress-coping strategies in early childhood education and secondary education might theoretically have potential beneficial effects on the subsequent risk of MS development or symptom flare-up, depending on a variety of factors.

But for now, when patients and colleagues ask me, “Can acute emotional stress be a ‘trigger’ for MS symptomology?,” my answer will remain, “Potentially, until proven otherwise.”

Key clinical point: Although a few biomarkers can assist in distinguishing psoriatic arthritis (PsA) from psoriasis or osteoarthritis, a precise diagnostic biomarker that can distinguish PsA from osteoarthritis and most other chronic inflammatory diseases has not yet been identified.

Major finding: Serum cartilage oligometrix metalloproteinase levels were significantly increased in patients with PsA compared with control individuals without chronic inflammatory diseases (standardized mean difference [SMD] 2.305; P = .003) and patients with osteoarthritis (SMD 0.783; P = .046). Serum matrix metalloproteinase-3 levels were significantly higher in patients with PsA vs psoriasis (SMD 0.419; P = .006) but could not distinguish patients with PsA from control individuals.

Study details: Findings are from a meta-analysis of 124 studies including patients with PsA.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Wirth T et al. Biomarkers in psoriatic arthritis: A meta-analysis and systematic review. Front Immunol. 2022;13:1054539 (Nov 30). Doi: 10.3389/fimmu.2022.1054539

Key clinical point: Although a few biomarkers can assist in distinguishing psoriatic arthritis (PsA) from psoriasis or osteoarthritis, a precise diagnostic biomarker that can distinguish PsA from osteoarthritis and most other chronic inflammatory diseases has not yet been identified.

Major finding: Serum cartilage oligometrix metalloproteinase levels were significantly increased in patients with PsA compared with control individuals without chronic inflammatory diseases (standardized mean difference [SMD] 2.305; P = .003) and patients with osteoarthritis (SMD 0.783; P = .046). Serum matrix metalloproteinase-3 levels were significantly higher in patients with PsA vs psoriasis (SMD 0.419; P = .006) but could not distinguish patients with PsA from control individuals.

Study details: Findings are from a meta-analysis of 124 studies including patients with PsA.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Wirth T et al. Biomarkers in psoriatic arthritis: A meta-analysis and systematic review. Front Immunol. 2022;13:1054539 (Nov 30). Doi: 10.3389/fimmu.2022.1054539

Key clinical point: Although a few biomarkers can assist in distinguishing psoriatic arthritis (PsA) from psoriasis or osteoarthritis, a precise diagnostic biomarker that can distinguish PsA from osteoarthritis and most other chronic inflammatory diseases has not yet been identified.

Major finding: Serum cartilage oligometrix metalloproteinase levels were significantly increased in patients with PsA compared with control individuals without chronic inflammatory diseases (standardized mean difference [SMD] 2.305; P = .003) and patients with osteoarthritis (SMD 0.783; P = .046). Serum matrix metalloproteinase-3 levels were significantly higher in patients with PsA vs psoriasis (SMD 0.419; P = .006) but could not distinguish patients with PsA from control individuals.

Study details: Findings are from a meta-analysis of 124 studies including patients with PsA.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Wirth T et al. Biomarkers in psoriatic arthritis: A meta-analysis and systematic review. Front Immunol. 2022;13:1054539 (Nov 30). Doi: 10.3389/fimmu.2022.1054539

Key clinical point: Axial psoriatic arthritis (PsA) can be categorized as a distinct subtype of PsA because it exhibits clinical and radiological symptoms that are different from those of ankylosing spondylitis (AS) with psoriasis.

Major finding: Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27-negative axial PsA had lesser inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001) along with a higher prevalence of nail disease (P = .009) and were more likely to present with psoriasis before spondyloarthritis onset (P = .020). However, patients with HLA-B27-positive axial PsA vs AS and psoriasis reported lesser structural damage as revealed by Bath Ankylosing Spondylitis Radiology Index scores (P < .001).

Study details: This cross-sectional study included 109 patients with axial PsA and 127 patients with AS and current presentation or a history of skin psoriasis from the REGISPONSER registry.

Disclosures: The REGISPONSER registry is funded by the Spanish Society for Rheumatology. The authors declared no conflicts of interest.

Source: Michelena X et al. Characterising the axial phenotype of psoriatic arthritis: a study comparing axial psoriatic arthritis and ankylosing spondylitis with psoriasis from the REGISPONSER registry. RMD Open. 2022;8:e002513 (Dec 5). Doi: 10.1136/rmdopen-2022-002513

Key clinical point: Axial psoriatic arthritis (PsA) can be categorized as a distinct subtype of PsA because it exhibits clinical and radiological symptoms that are different from those of ankylosing spondylitis (AS) with psoriasis.

Major finding: Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27-negative axial PsA had lesser inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001) along with a higher prevalence of nail disease (P = .009) and were more likely to present with psoriasis before spondyloarthritis onset (P = .020). However, patients with HLA-B27-positive axial PsA vs AS and psoriasis reported lesser structural damage as revealed by Bath Ankylosing Spondylitis Radiology Index scores (P < .001).

Study details: This cross-sectional study included 109 patients with axial PsA and 127 patients with AS and current presentation or a history of skin psoriasis from the REGISPONSER registry.

Disclosures: The REGISPONSER registry is funded by the Spanish Society for Rheumatology. The authors declared no conflicts of interest.

Source: Michelena X et al. Characterising the axial phenotype of psoriatic arthritis: a study comparing axial psoriatic arthritis and ankylosing spondylitis with psoriasis from the REGISPONSER registry. RMD Open. 2022;8:e002513 (Dec 5). Doi: 10.1136/rmdopen-2022-002513

Key clinical point: Axial psoriatic arthritis (PsA) can be categorized as a distinct subtype of PsA because it exhibits clinical and radiological symptoms that are different from those of ankylosing spondylitis (AS) with psoriasis.

Major finding: Compared with patients with AS and psoriasis, patients with human leukocyte antigen (HLA)-B27-negative axial PsA had lesser inflammatory pain (P = .002), anterior uveitis (P = .014), and structural damage (P < .001) along with a higher prevalence of nail disease (P = .009) and were more likely to present with psoriasis before spondyloarthritis onset (P = .020). However, patients with HLA-B27-positive axial PsA vs AS and psoriasis reported lesser structural damage as revealed by Bath Ankylosing Spondylitis Radiology Index scores (P < .001).

Study details: This cross-sectional study included 109 patients with axial PsA and 127 patients with AS and current presentation or a history of skin psoriasis from the REGISPONSER registry.

Disclosures: The REGISPONSER registry is funded by the Spanish Society for Rheumatology. The authors declared no conflicts of interest.

Source: Michelena X et al. Characterising the axial phenotype of psoriatic arthritis: a study comparing axial psoriatic arthritis and ankylosing spondylitis with psoriasis from the REGISPONSER registry. RMD Open. 2022;8:e002513 (Dec 5). Doi: 10.1136/rmdopen-2022-002513

Key clinical point: Smoking and alcohol consumption were associated with a lower prevalence of arthritis and peripheral manifestations in patients with psoriatic arthritis (PsA).

Major finding: Smoking was associated with a lower prevalence of arthritis ever (odds ratio [OR] 0.63; 95% CI 0.41-0.95), and current alcohol consumption was associated with a lower prevalence of current arthritis or enthesitis (OR 0.61; 95% CI 0.47-0.79), current arthritis alone (OR 0.69; 95% CI 0.53-0.90), and current enthesitis alone (OR 0.49; 95% CI, 0.34-0.71).

Study details: Findings are from a multinational, cross-sectional study including patients with axial spondyloarthritis (n = 2717), peripheral spondyloarthritis (n = 432), and PsA (n = 1032).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ladehesa-Pineda ML et al. Smoking and alcohol consumption are associated with peripheral musculoskeletal involvement in patients with spondyloarthritis (including psoriatic arthritis). Results from the ASAS-PerSpA study. Semin Arthritis Rheum. 2022;58:152146 (Nov 30). Doi: 10.1016/j.semarthrit.2022.152146

Key clinical point: Smoking and alcohol consumption were associated with a lower prevalence of arthritis and peripheral manifestations in patients with psoriatic arthritis (PsA).

Major finding: Smoking was associated with a lower prevalence of arthritis ever (odds ratio [OR] 0.63; 95% CI 0.41-0.95), and current alcohol consumption was associated with a lower prevalence of current arthritis or enthesitis (OR 0.61; 95% CI 0.47-0.79), current arthritis alone (OR 0.69; 95% CI 0.53-0.90), and current enthesitis alone (OR 0.49; 95% CI, 0.34-0.71).

Study details: Findings are from a multinational, cross-sectional study including patients with axial spondyloarthritis (n = 2717), peripheral spondyloarthritis (n = 432), and PsA (n = 1032).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ladehesa-Pineda ML et al. Smoking and alcohol consumption are associated with peripheral musculoskeletal involvement in patients with spondyloarthritis (including psoriatic arthritis). Results from the ASAS-PerSpA study. Semin Arthritis Rheum. 2022;58:152146 (Nov 30). Doi: 10.1016/j.semarthrit.2022.152146

Key clinical point: Smoking and alcohol consumption were associated with a lower prevalence of arthritis and peripheral manifestations in patients with psoriatic arthritis (PsA).

Major finding: Smoking was associated with a lower prevalence of arthritis ever (odds ratio [OR] 0.63; 95% CI 0.41-0.95), and current alcohol consumption was associated with a lower prevalence of current arthritis or enthesitis (OR 0.61; 95% CI 0.47-0.79), current arthritis alone (OR 0.69; 95% CI 0.53-0.90), and current enthesitis alone (OR 0.49; 95% CI, 0.34-0.71).

Study details: Findings are from a multinational, cross-sectional study including patients with axial spondyloarthritis (n = 2717), peripheral spondyloarthritis (n = 432), and PsA (n = 1032).

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Ladehesa-Pineda ML et al. Smoking and alcohol consumption are associated with peripheral musculoskeletal involvement in patients with spondyloarthritis (including psoriatic arthritis). Results from the ASAS-PerSpA study. Semin Arthritis Rheum. 2022;58:152146 (Nov 30). Doi: 10.1016/j.semarthrit.2022.152146

Key clinical point: Cognitive abilities were altered in patients with psoriatic arthritis (PsA) compared with non-rheumatology reference individuals, with significant impairment in selective attention.

Major finding: Patients with PsA reported significant deficits in selective attention (mean difference [MD] −4.5), no effect on working memory (P = .662) and improvement in episodic short-term memory (MD 3.0; both P < .001) compared with matched reference subjects.

Study details: Findings are from a cross-sectional, exploratory study including 101 patients with axial spondyloarthritis, 117 patients with PsA, and matched non-rheumatology reference subjects without any diseases relevant to cognitive performance.

Disclosures: This study was funded by the RHADAR GbR, Germany. Some authors, including the lead author, declared receiving grants, consulting fees, speaker’s fees, travel support, honoraria, or advisory board support from several sources.

Source: Kleinert S et al. Impairment in cognitive function in patients with axial spondyloarthritis and psoriatic arthritis. Rheumatol Int. 2022 (Nov 28). Doi: 10.1007/s00296-022-05248-4

Key clinical point: Cognitive abilities were altered in patients with psoriatic arthritis (PsA) compared with non-rheumatology reference individuals, with significant impairment in selective attention.

Major finding: Patients with PsA reported significant deficits in selective attention (mean difference [MD] −4.5), no effect on working memory (P = .662) and improvement in episodic short-term memory (MD 3.0; both P < .001) compared with matched reference subjects.

Study details: Findings are from a cross-sectional, exploratory study including 101 patients with axial spondyloarthritis, 117 patients with PsA, and matched non-rheumatology reference subjects without any diseases relevant to cognitive performance.

Disclosures: This study was funded by the RHADAR GbR, Germany. Some authors, including the lead author, declared receiving grants, consulting fees, speaker’s fees, travel support, honoraria, or advisory board support from several sources.

Source: Kleinert S et al. Impairment in cognitive function in patients with axial spondyloarthritis and psoriatic arthritis. Rheumatol Int. 2022 (Nov 28). Doi: 10.1007/s00296-022-05248-4

Key clinical point: Cognitive abilities were altered in patients with psoriatic arthritis (PsA) compared with non-rheumatology reference individuals, with significant impairment in selective attention.

Major finding: Patients with PsA reported significant deficits in selective attention (mean difference [MD] −4.5), no effect on working memory (P = .662) and improvement in episodic short-term memory (MD 3.0; both P < .001) compared with matched reference subjects.

Study details: Findings are from a cross-sectional, exploratory study including 101 patients with axial spondyloarthritis, 117 patients with PsA, and matched non-rheumatology reference subjects without any diseases relevant to cognitive performance.

Disclosures: This study was funded by the RHADAR GbR, Germany. Some authors, including the lead author, declared receiving grants, consulting fees, speaker’s fees, travel support, honoraria, or advisory board support from several sources.

Source: Kleinert S et al. Impairment in cognitive function in patients with axial spondyloarthritis and psoriatic arthritis. Rheumatol Int. 2022 (Nov 28). Doi: 10.1007/s00296-022-05248-4

Key clinical point: Increasing disease activity and joint damage were significant risk factors for requiring musculoskeletal (MSK) surgery in patients with psoriatic arthritis (PsA).

Major finding: A greater number of damaged joints (hazard ratio [HR] 1.032; P < .001), presence of nail lesions (HR 2.079; P < .006), higher health assessment questionnaire scores (HR 2.012; P < .001), an elevated erythrocyte sedimentation rate (HR 2.365; P = .017), a greater number of actively inflamed joints (HR 1.037; P = .007), and human leukocyte antigen-B*27 positivity (HR 2.217; P = .048) were associated with an increased risk for surgery.

Study details: Findings are from a longitudinal, observational cohort study including 1574 patients with PsA, of which 11.8% underwent ≥1 MSK surgery attributable to PsA.

Disclosures: This study was supported by the Krembil Foundation, Toronto. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Musculoskeletal surgery in psoriatic arthritis: Prevalence and risk factors. J Rheumatol. 2022 (Nov 15). Doi: 10.3899/jrheum.220908

Key clinical point: Increasing disease activity and joint damage were significant risk factors for requiring musculoskeletal (MSK) surgery in patients with psoriatic arthritis (PsA).

Major finding: A greater number of damaged joints (hazard ratio [HR] 1.032; P < .001), presence of nail lesions (HR 2.079; P < .006), higher health assessment questionnaire scores (HR 2.012; P < .001), an elevated erythrocyte sedimentation rate (HR 2.365; P = .017), a greater number of actively inflamed joints (HR 1.037; P = .007), and human leukocyte antigen-B*27 positivity (HR 2.217; P = .048) were associated with an increased risk for surgery.

Study details: Findings are from a longitudinal, observational cohort study including 1574 patients with PsA, of which 11.8% underwent ≥1 MSK surgery attributable to PsA.

Disclosures: This study was supported by the Krembil Foundation, Toronto. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Musculoskeletal surgery in psoriatic arthritis: Prevalence and risk factors. J Rheumatol. 2022 (Nov 15). Doi: 10.3899/jrheum.220908

Key clinical point: Increasing disease activity and joint damage were significant risk factors for requiring musculoskeletal (MSK) surgery in patients with psoriatic arthritis (PsA).

Major finding: A greater number of damaged joints (hazard ratio [HR] 1.032; P < .001), presence of nail lesions (HR 2.079; P < .006), higher health assessment questionnaire scores (HR 2.012; P < .001), an elevated erythrocyte sedimentation rate (HR 2.365; P = .017), a greater number of actively inflamed joints (HR 1.037; P = .007), and human leukocyte antigen-B*27 positivity (HR 2.217; P = .048) were associated with an increased risk for surgery.

Study details: Findings are from a longitudinal, observational cohort study including 1574 patients with PsA, of which 11.8% underwent ≥1 MSK surgery attributable to PsA.

Disclosures: This study was supported by the Krembil Foundation, Toronto. The authors declared no conflicts of interest.

Source: Kwok TSH et al. Musculoskeletal surgery in psoriatic arthritis: Prevalence and risk factors. J Rheumatol. 2022 (Nov 15). Doi: 10.3899/jrheum.220908

Key clinical point: Psoriatic arthritis (PsA) was positively associated with Crohn’s disease and genetically predicted Crohn’s disease was associated with an increased risk for PsA, indicating a bidirectional causal relationship between the 2 diseases.

Major finding: PsA was associated with a 31.9% increased risk for Crohn’s disease (odds ratio [OR] 1.319; P < .001) and genetically predicted Crohn’s disease was linked to a 44.8% higher risk for PsA (OR 1.448; P = .001).

Study details: Findings are from a bidirectional 2-sample mendelian randomization study including 4510 patients with psoriasis, 1637 patients with PsA, and 212,242 control individuals along with 657 patients with Crohn’s disease, 2251 patients with ulcerative colitis, and 210,300 control individuals.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sun Y et al. The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Sci Rep. 2022;12:20526 (Nov 28). Doi: 10.1038/s41598-022-24872-5

Key clinical point: Psoriatic arthritis (PsA) was positively associated with Crohn’s disease and genetically predicted Crohn’s disease was associated with an increased risk for PsA, indicating a bidirectional causal relationship between the 2 diseases.

Major finding: PsA was associated with a 31.9% increased risk for Crohn’s disease (odds ratio [OR] 1.319; P < .001) and genetically predicted Crohn’s disease was linked to a 44.8% higher risk for PsA (OR 1.448; P = .001).

Study details: Findings are from a bidirectional 2-sample mendelian randomization study including 4510 patients with psoriasis, 1637 patients with PsA, and 212,242 control individuals along with 657 patients with Crohn’s disease, 2251 patients with ulcerative colitis, and 210,300 control individuals.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sun Y et al. The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Sci Rep. 2022;12:20526 (Nov 28). Doi: 10.1038/s41598-022-24872-5

Key clinical point: Psoriatic arthritis (PsA) was positively associated with Crohn’s disease and genetically predicted Crohn’s disease was associated with an increased risk for PsA, indicating a bidirectional causal relationship between the 2 diseases.

Major finding: PsA was associated with a 31.9% increased risk for Crohn’s disease (odds ratio [OR] 1.319; P < .001) and genetically predicted Crohn’s disease was linked to a 44.8% higher risk for PsA (OR 1.448; P = .001).

Study details: Findings are from a bidirectional 2-sample mendelian randomization study including 4510 patients with psoriasis, 1637 patients with PsA, and 212,242 control individuals along with 657 patients with Crohn’s disease, 2251 patients with ulcerative colitis, and 210,300 control individuals.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sun Y et al. The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Sci Rep. 2022;12:20526 (Nov 28). Doi: 10.1038/s41598-022-24872-5