VARSITY: Better histologic outcomes with vedolizumab than adalimumab in UC

Emerging UC targets include histology
Article Type
Changed
Thu, 09/09/2021 - 11:07

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

Body

 

Dr. Robin Dalal
Over the past decade, there have been evolving goals in the treatment of inflammatory bowel disease patients. Goals of treatment now go further than symptom-based remission, and health care providers strive for endoscopic remission to improve quality of life and prevent disease complications. In the past few years, there has been growing evidence that histologic remission in ulcerative colitis (UC) may be a more beneficial target to achieve. This study by Peyrin-Biroulet and colleagues explores histologic outcomes within the VARSITY trial with the finding that vedolizumab led to more patients achieving histologic improvement, compared with those who were randomized to adalimumab. The findings of histologic improvement with vedolizumab in this study parallel the “larger” outcomes of the VARSITY trial, which found that vedolizumab provided superior clinical remission and endoscopic improvement at week 52.

Another important element of this study was the exploration of association between endoscopic and histologic outcomes using two validated histologic indices (the Geboes Index score and the Robarts Histopathology Index). While both indices showed moderate agreement overall between histologic activity and endoscopic improvement, the Robarts score correlated better with endoscopic improvement. Therefore, the authors propose that the Robarts scoring system may be the better index for assessing histologic outcomes. This is important because standardized scoring systems would be needed to translate histologic outcomes as a goal in real clinical practice.

The landscape continues to evolve for treatment goals in UC. Symptom control is the tip of the iceberg and endoscopic along with histologic control may lead to a more durable remission.

Robin Dalal, MD, is an assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn. She has nothing to disclose.

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Body

 

Dr. Robin Dalal
Over the past decade, there have been evolving goals in the treatment of inflammatory bowel disease patients. Goals of treatment now go further than symptom-based remission, and health care providers strive for endoscopic remission to improve quality of life and prevent disease complications. In the past few years, there has been growing evidence that histologic remission in ulcerative colitis (UC) may be a more beneficial target to achieve. This study by Peyrin-Biroulet and colleagues explores histologic outcomes within the VARSITY trial with the finding that vedolizumab led to more patients achieving histologic improvement, compared with those who were randomized to adalimumab. The findings of histologic improvement with vedolizumab in this study parallel the “larger” outcomes of the VARSITY trial, which found that vedolizumab provided superior clinical remission and endoscopic improvement at week 52.

Another important element of this study was the exploration of association between endoscopic and histologic outcomes using two validated histologic indices (the Geboes Index score and the Robarts Histopathology Index). While both indices showed moderate agreement overall between histologic activity and endoscopic improvement, the Robarts score correlated better with endoscopic improvement. Therefore, the authors propose that the Robarts scoring system may be the better index for assessing histologic outcomes. This is important because standardized scoring systems would be needed to translate histologic outcomes as a goal in real clinical practice.

The landscape continues to evolve for treatment goals in UC. Symptom control is the tip of the iceberg and endoscopic along with histologic control may lead to a more durable remission.

Robin Dalal, MD, is an assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn. She has nothing to disclose.

Body

 

Dr. Robin Dalal
Over the past decade, there have been evolving goals in the treatment of inflammatory bowel disease patients. Goals of treatment now go further than symptom-based remission, and health care providers strive for endoscopic remission to improve quality of life and prevent disease complications. In the past few years, there has been growing evidence that histologic remission in ulcerative colitis (UC) may be a more beneficial target to achieve. This study by Peyrin-Biroulet and colleagues explores histologic outcomes within the VARSITY trial with the finding that vedolizumab led to more patients achieving histologic improvement, compared with those who were randomized to adalimumab. The findings of histologic improvement with vedolizumab in this study parallel the “larger” outcomes of the VARSITY trial, which found that vedolizumab provided superior clinical remission and endoscopic improvement at week 52.

Another important element of this study was the exploration of association between endoscopic and histologic outcomes using two validated histologic indices (the Geboes Index score and the Robarts Histopathology Index). While both indices showed moderate agreement overall between histologic activity and endoscopic improvement, the Robarts score correlated better with endoscopic improvement. Therefore, the authors propose that the Robarts scoring system may be the better index for assessing histologic outcomes. This is important because standardized scoring systems would be needed to translate histologic outcomes as a goal in real clinical practice.

The landscape continues to evolve for treatment goals in UC. Symptom control is the tip of the iceberg and endoscopic along with histologic control may lead to a more durable remission.

Robin Dalal, MD, is an assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn. She has nothing to disclose.

Title
Emerging UC targets include histology
Emerging UC targets include histology

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

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Elderly mice receive the gift of warmth

Article Type
Changed
Thu, 09/09/2021 - 10:58

 

Steal from the warm, give to the cold

If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.

Elena Korenbaum/iStockphoto

Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.

Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.

The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
 

Grocery store tapping your subconscious? It’s a good thing

We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?

PxHere

In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.

You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.

The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.

So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
 

 

 

TikTokers take on tics

We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?

Bicanski/Pixnio

TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.

There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.

Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”

There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”

Who would have guessed that people would disagree over stuff on the Internet?
 

Look on the bright side: Obesity edition

The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.

© okeyphotos/iStockphoto.com

As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.

Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.

A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.

These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.

A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.

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Topics
Sections

 

Steal from the warm, give to the cold

If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.

Elena Korenbaum/iStockphoto

Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.

Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.

The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
 

Grocery store tapping your subconscious? It’s a good thing

We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?

PxHere

In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.

You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.

The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.

So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
 

 

 

TikTokers take on tics

We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?

Bicanski/Pixnio

TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.

There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.

Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”

There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”

Who would have guessed that people would disagree over stuff on the Internet?
 

Look on the bright side: Obesity edition

The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.

© okeyphotos/iStockphoto.com

As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.

Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.

A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.

These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.

A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.

 

Steal from the warm, give to the cold

If there’s one constant in life other than taxes, it’s elderly people moving to Florida. The Sunshine State’s reputation as a giant retirement home needs no elaboration, but why do senior citizens gravitate there? Well, many reasons, but a big one is that, the older you get, the more susceptible and sensitive you are to the cold. And now, according to a new study, we may have identified a culprit.

Elena Korenbaum/iStockphoto

Researchers from Yale University examined a group of mice and found that the older ones lacked ICL2 cells in their fatty tissue. These cells, at least in younger mice, help restore body heat when exposed to cold temperatures. Lacking these cells meant that older mice had a limited ability to burn their fat and raise their temperature in response to cold.

Well, job done, all we need to do now is stimulate production of ICL2 cells in elderly people, and they’ll be able to go outside in 80-degree weather without a sweater again. Except there’s a problem. In a cruel twist of fate, when the elderly mice were given a molecule to boost ICL2 cell production, they actually became less tolerant of the cold than at baseline. Oops.

The scientists didn’t give up though, and gave their elderly mice ICL2 cells from young mice. This finally did the trick, though we have to admit, if that treatment does eventually scale up to humans, the prospect of a bunch of senior citizens taking ICL2 cells from young people to stay warm does sound a bit like a bad vampire movie premise. “I vant to suck your immune cell group 2 innate lymphoid cells!” Not the most pithy catch phrase in the world.
 

Grocery store tapping your subconscious? It’s a good thing

We all know there’s marketing and functionality elements to grocery stores and how they’re set up for your shopping pleasure. But what if I told you that the good old supermarket subconscious trick works on how healthy food decisions are?

PxHere

In a recent study, researchers at the University of Southampton in England found that if you placed a wider selection of fruits and vegetables near the entrances and more nonfood items near checkouts, sales decreased on the sweets and increased on the produce. “The findings of our study suggest that a healthier store layout could lead to nearly 10,000 extra portions of fruit and vegetables and approximately 1,500 fewer portions of confectionery being sold on a weekly basis in each store,” lead author Dr. Christina Vogel explained.

You’re probably thinking that food placement studies aren’t new. That’s true, but this one went above and beyond. Instead of just looking at the influence placement has on purchase, this one took it further by trying to reduce the consumers’ “calorie opportunities” and examining the effect on sales. Also, customer loyalty, patterns, and diets were taken into account across multiple household members.

The researchers think shifting the layouts in grocery stores could shift people’s food choices, producing a domino effect on the population’s overall diet. With obesity, diabetes, and cardiology concerns always looming, swaying consumers toward healthier food choices makes for better public health overall.

So if you feel like you’re being subconsciously assaulted by veggies every time you walk into Trader Joe’s, just know it’s for your own good.
 

 

 

TikTokers take on tics

We know TikTok is what makes a lot of teens and young adults tick, but what if TikTokers are actually catching tic disorders from other TikTokers?

Bicanski/Pixnio

TikTok blew up during the pandemic. Many people were stuck at home and had nothing better to do than make and watch TikTok videos. The pandemic brought isolation, uncertainty, and anxiety. The stress that followed may have caused many people, mostly women and young girls, to develop tic disorders.

There’s a TikTok for everything, whether it’s a new dance or a recipe. Many people even use TikTok to speak out about their illnesses. Several TikTokers have Tourette’s syndrome and show their tics on their videos. It appears that some audience members actually “catch” the tics from watching the videos and are then unable to stop certain jerking movements or saying specific words.

Neurologists at the University of Calgary (Alta.), who were hearing from colleagues and getting referrals of such patients, called it “an epidemic within the pandemic.” The behavior is not actually Tourette’s, they told Vice, but the patients “cannot stop, and we have absolutely witnessed that.”

There is, of course, controversy over the issue. One individual with the condition said, “I feel like there’s a lot of really weird, backwards stigma on TikTok about tic disorders. Like, you aren’t allowed to have one unless it’s this one.”

Who would have guessed that people would disagree over stuff on the Internet?
 

Look on the bright side: Obesity edition

The pandemic may have postponed “Top Gun: Maverick” and “The Marvelous Mrs. Maisel” until who-knows-when, but we here at LOTME are happy to announce the nearly-as-anticipated return of Bacteria vs. the World.

© okeyphotos/iStockphoto.com

As you may recall from our last edition of BVTW, bacteria battled the ghost of Charles Darwin, who had taken the earthly form of antibiotics capable of stopping bacterial evolution. Tonight, our prokaryotic protagonists take on an equally relentless and ubiquitous challenger: obesity.

Specifically, we’re putting bacteria up against the obesity survival paradox, that phenomenon in which obesity and overweight seem to protect against – yes, you guessed it – bacterial infections.

A Swedish research team observed a group of 2,196 individual adults who received care for suspected severe bacterial infection at Skaraborg Hospital in Skövde. One year after hospitalization, 26% of normal-weight (body mass index, 18.5-24.99) patients were dead, compared with 17% of overweight (BMI, 25.0-29.99), 16% of obese (BMI, 30.0-34.99), and 9% of very obese (BMI >35) patients.

These results confirm the obesity survival paradox, but “what we don’t know is how being overweight can benefit the patient with a bacterial infection, or whether it’s connected with functions in the immune system and how they’re regulated,” lead author Dr. Åsa Alsiö said in a written statement.

A spokes-cell for the bacteria disputed the results and challenged the legitimacy of the investigators. When asked if there should be some sort of reexamination of the findings, he/she/it replied: “You bet your flagella.” We then pointed out that humans don’t have flagellum, and the representative raised his/her/its flagella in what could only be considered an obscene gesture.

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Modifier -25 and the New 2021 E/M Codes: Documentation of Separate and Distinct Just Got Easier

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Mon, 09/13/2021 - 12:08

 

Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.1 Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.7 Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.8 Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”1 Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.9 In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.10 Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services11: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.11 Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.10 The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.



Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

References
  1. Current Procedural Terminology 2021, Professional Edition. American Medical Association; 2020.
  2. Rogers HW. Modifier 25 victory, but the battle is not over. Cutis. 2018;101:409-410.
  3. Rogers HW. One diagnosis and modifier 25: appropriate or audit target? Cutis. 2017;99:165-166.
  4. Update regarding E/M with modifier 25—professional. Anthem Blue Cross Blue Shield website. Published February 1, 2019. Accessed August 17, 2021. https://providernews.anthem.com/ohio/article/update-regarding-em-with-modifier-25-professional
  5. Payment policies—surgery. Harvard Pilgrim Health Care website. Updated May 2021. Accessed August 17, 2021. https://www.harvardpilgrim.org/provider/wp-content/uploads/sites/7/2020/07/H-6-Surgery-PM.pdf
  6. Modifier 25: frequently asked questions. Independence Blue Cross website. Updated September 25, 2017. Accessed August 17, 2021. https://provcomm.ibx.com/ibc/archive/pages/A86603B03881756B8525817E00768006.aspx
  7. Huang G. CMS 2019 fee schedule takes modifier 25 cuts, runs with them. Doctors Management website. Accessed August 17, 2021. https://www.doctors-management.com/cms-2019-feeschedule-modifier25/
  8. Dermatologist claims for evaluation and management services on the same day as minor surgical procedures. US Department of Health and Humans Services Office of Inspector General website. Accessed August 17, 2021. https://oig.hhs.gov/reports-and-publications/workplan/summary/wp-summary-0000577.asp
  9. Global surgery booklet. Centers for Medicare and Medicaid Services website. Updated September 2018. Accessed August 17, 2021. https://www.cms.gov/outreach-and-education/medicare-learning-network-mln/mlnproducts/downloads/globallsurgery-icn907166.pdf
  10. American Medical Association. CPT® Evaluation and management (E/M)—office or other outpatient (99202-99215) and prolonged services (99354, 99355, 99356, 99417) code and guideline changes. Updated March 9, 2021. Accessed August 17, 2021. https://www.ama-assn.org/system/files/2019-06/cpt-office-prolonged-svs-code-changes.pdf
  11. 1997 documentation guidelines for evaluation and management services. Centers for Medicare and Medicaid Services website. Accessed August 17, 2021. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNEdWebGuide/Downloads/97Docguidelines.pdf
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The author reports no conflict of interest.

Correspondence: Howard W. Rogers, MD, PhD, 111 Salem Turnpike, Ste 7, Norwich, CT 06360 ([email protected]).

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Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.1 Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.7 Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.8 Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”1 Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.9 In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.10 Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services11: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.11 Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.10 The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.



Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

 

Insurers Target Modifier -25

Modifier -25 allows reporting of both a minor procedure (ie, one with a 0- or 10-day global period) and a separate and distinct evaluation and management (E/M) service on the same date of service.1 Because of the multicomplaint nature of dermatology, the ability to report a same-day procedure and an E/M service is critical for efficient, cost-effective, and patient-centered dermatologic care. However, it is well known that the use of modifier -25 has been under notable insurer scrutiny and is a common reason for medical record audits.2,3 Some insurers have responded to increased utilization of modifier -25 by cutting reimbursement for claims that include both a procedure and an E/M service or by denying one of the services altogether.4-6 The Centers for Medicare and Medicaid Services also have expressed concern about this coding combination with proposed cuts to reimbursement.7 Moreover, the Office of Inspector General has announced a work plan to investigate the frequent utilization of E/M codes and minor procedures by dermatologists.8 Clearly, modifier -25 is a continued target by insurers and regulators; therefore, dermatologists will want to make sure their coding and documentation meet all requirements and are updated for the new E/M codes for 2021.

The American Medical Association’s Current Procedural Terminology indicates that modifier -25 allows reporting of a “significant, separately identifiable evaluation and management service by the same physician or other qualified health care professional on the same day of a procedure or other service.”1 Given that dermatology patients typically present with multiple concerns, dermatologists commonly evaluate and treat numerous conditions during one visit. Understanding what constitutes a separately identifiable E/M service is critical to bill accurately and to pass insurer audits.

Global Surgical Package

To appropriately bill both a procedure and an E/M service, the physician must indicate that the patient’s condition required an E/M service above and beyond the usual work of the procedure. The compilation of evaluation and work included in the payment for a procedure is called the global surgical package.9 In general, the global surgical package includes local or topical anesthesia; the surgical service/procedure itself; immediate postoperative care, including dictating the operative note; meeting/discussing the patient’s procedure with family and other physicians; and writing orders for the patient. For minor procedures (ie, those with either 0- or 10-day global periods), the surgical package also includes same-day E/M services associated with the decision to perform surgery. An appropriate history and physical examination as well as a discussion of the differential diagnosis, treatment options, and risk and benefits of treatment are all included in the payment of a minor procedure itself. Therefore, an evaluation to discuss a patient’s condition or change in condition, alternatives to treatment, or next steps after a diagnosis related to a treatment or diagnostic procedure should not be separately reported. Moreover, the fact that the patient is new to the physician is not in itself sufficient to allow reporting of an E/M service with these minor procedures. For major procedures (ie, those with 90-day postoperative periods), the decision for surgery is excluded from the global surgical package.

2021 E/M Codes Simplify Documentation

The biggest coding change of 2021 was the new E/M codes.10 Prior to this year, the descriptors of E/M services recognized 7 components to define the levels of E/M services11: history and nature of the presenting problem; physical examination; medical decision-making (MDM); counseling; coordination of care; and time. Furthermore, history, physical examination, and MDM were all broken down into more granular elements that were summed to determine the level for each component; for example, the history of the presenting problem was defined as a chronological description of the development of the patient’s present illness, including the following elements: location, quality, severity, duration, timing, context, modifying factors, and associated signs and symptoms. Each of these categories would constitute bullet points to be summed to determine the level of history. Physical examination and MDM bullet points also would be summed to determine a proper coding level.11 Understandably, this coding scheme was complicated and burdensome to medical providers.

The redefinition of the E/M codes for 2021 substantially simplified the determination of coding level and documentation.10 The revisions to the E/M office visit code descriptors and documentation standards are now centered around how physicians think and take care of patients and not on mandatory standards and checking boxes. The main changes involve MDM as the prime determinant of the coding level. Elements of MDM affecting coding for an outpatient or office visit now include only 3 components: the number and complexity of problems addressed in the encounter, the amount or complexity of data to be reviewed and analyzed, and the risk of complications or morbidity of patient management. Gone are the requirements from the earlier criteria requiring so many bullet points for the history, physical examination, and MDM.

Dermatologists may ask, “How does the new E/M coding structure affect reporting and documenting an E/M and a procedure on the same day?” The answer is that the determination of separate and distinct is basically unchanged with the new E/M codes; however, the documentation requirements for modifier -25 using the new E/M codes are simplified.

As always, the key to determining whether a separate and distinct E/M service was provided and subsequently documented is to deconstruct the medical note. All evaluation services associated with the procedure—making a clinical diagnosis or differential diagnosis, decision to perform surgery, and discussion of alternative treatments—should be removed from one’s documentation as shown in the example below. If a complete E/M service still exists, then an E/M may be billed in addition to the procedure. Physical examination of the treatment area is included in the surgical package. With the prior E/M criteria, physical examination of the procedural area could not be used again as a bullet point to count for the E/M level. However, with the new 2021 coding requirements, the documentation of a separate MDM will be sufficient to meet criteria because documentation of physical examination is not a requirement.

Modifier -25 Examples

Let’s examine a typical dermatologist medical note. An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. The patient also complains of a growing tender lesion on the left elbow of 2 months’ duration. Physical examination reveals a linear vesicular eruption on the left wrist and a tender hyperkeratotic papule on the left elbow. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed. The decision is made to perform a tangential biopsy of the lesion on the left elbow because of the suspicion for malignancy. The biopsy is performed the same day.

This case clearly illustrates performance of an E/M service in the treatment of rhus dermatitis, which is separate and distinct from the biopsy procedure; however, in evaluating whether the case meets the documentation requirements for modifier -25, the information in the medical note inclusive to the procedure’s global surgical package, including history associated with establishing the diagnosis, physical examination of the procedure area(s), and discussion of treatment options, is eliminated, leaving the following notes: An established patient presents to the dermatologist complaining of an itchy rash on the left wrist after a hiking trip. Treatment with topical hydrocortisone 1% did not help. No data is evaluated. A diagnosis of acute rhus dermatitis of the left wrist is made, and betamethasone cream is prescribed.



Because the physical examination of the body part (left arm) is included in the procedure’s global surgical package, the examination of the left wrist cannot be used as coding support for the E/M service. This makes a difference for coding level in the prior E/M coding requirements, which required examination bullet points. However, with the 2021 E/M codes, documentation of physical examination bullet points is irrelevant to the coding level. Therefore, qualifying for a modifier -25 claim is more straightforward in this case with the new code set. Because bullet points are not integral to the 2021 E/M codes, qualifying and properly documenting for a higher level of service will likely be more common in dermatology.

Final Thoughts

Frequent use of modifier -25 is a critical part of a high-quality and cost-effective dermatology practice. Same-day performance of minor procedures and E/M services allows for more rapid and efficient diagnosis and treatment of various conditions as well as minimizing unnecessary office visits. The new E/M codes for 2021 actually make the documentation of a separate and distinct E/M service less complicated because the bullet point requirements associated with the old E/M codes have been eliminated. Understanding how the new E/M code descriptors affect modifier -25 reporting and clear documentation of separate, distinct, and medically necessary E/M services will be needed due to increased insurer scrutiny and audits.

References
  1. Current Procedural Terminology 2021, Professional Edition. American Medical Association; 2020.
  2. Rogers HW. Modifier 25 victory, but the battle is not over. Cutis. 2018;101:409-410.
  3. Rogers HW. One diagnosis and modifier 25: appropriate or audit target? Cutis. 2017;99:165-166.
  4. Update regarding E/M with modifier 25—professional. Anthem Blue Cross Blue Shield website. Published February 1, 2019. Accessed August 17, 2021. https://providernews.anthem.com/ohio/article/update-regarding-em-with-modifier-25-professional
  5. Payment policies—surgery. Harvard Pilgrim Health Care website. Updated May 2021. Accessed August 17, 2021. https://www.harvardpilgrim.org/provider/wp-content/uploads/sites/7/2020/07/H-6-Surgery-PM.pdf
  6. Modifier 25: frequently asked questions. Independence Blue Cross website. Updated September 25, 2017. Accessed August 17, 2021. https://provcomm.ibx.com/ibc/archive/pages/A86603B03881756B8525817E00768006.aspx
  7. Huang G. CMS 2019 fee schedule takes modifier 25 cuts, runs with them. Doctors Management website. Accessed August 17, 2021. https://www.doctors-management.com/cms-2019-feeschedule-modifier25/
  8. Dermatologist claims for evaluation and management services on the same day as minor surgical procedures. US Department of Health and Humans Services Office of Inspector General website. Accessed August 17, 2021. https://oig.hhs.gov/reports-and-publications/workplan/summary/wp-summary-0000577.asp
  9. Global surgery booklet. Centers for Medicare and Medicaid Services website. Updated September 2018. Accessed August 17, 2021. https://www.cms.gov/outreach-and-education/medicare-learning-network-mln/mlnproducts/downloads/globallsurgery-icn907166.pdf
  10. American Medical Association. CPT® Evaluation and management (E/M)—office or other outpatient (99202-99215) and prolonged services (99354, 99355, 99356, 99417) code and guideline changes. Updated March 9, 2021. Accessed August 17, 2021. https://www.ama-assn.org/system/files/2019-06/cpt-office-prolonged-svs-code-changes.pdf
  11. 1997 documentation guidelines for evaluation and management services. Centers for Medicare and Medicaid Services website. Accessed August 17, 2021. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNEdWebGuide/Downloads/97Docguidelines.pdf
References
  1. Current Procedural Terminology 2021, Professional Edition. American Medical Association; 2020.
  2. Rogers HW. Modifier 25 victory, but the battle is not over. Cutis. 2018;101:409-410.
  3. Rogers HW. One diagnosis and modifier 25: appropriate or audit target? Cutis. 2017;99:165-166.
  4. Update regarding E/M with modifier 25—professional. Anthem Blue Cross Blue Shield website. Published February 1, 2019. Accessed August 17, 2021. https://providernews.anthem.com/ohio/article/update-regarding-em-with-modifier-25-professional
  5. Payment policies—surgery. Harvard Pilgrim Health Care website. Updated May 2021. Accessed August 17, 2021. https://www.harvardpilgrim.org/provider/wp-content/uploads/sites/7/2020/07/H-6-Surgery-PM.pdf
  6. Modifier 25: frequently asked questions. Independence Blue Cross website. Updated September 25, 2017. Accessed August 17, 2021. https://provcomm.ibx.com/ibc/archive/pages/A86603B03881756B8525817E00768006.aspx
  7. Huang G. CMS 2019 fee schedule takes modifier 25 cuts, runs with them. Doctors Management website. Accessed August 17, 2021. https://www.doctors-management.com/cms-2019-feeschedule-modifier25/
  8. Dermatologist claims for evaluation and management services on the same day as minor surgical procedures. US Department of Health and Humans Services Office of Inspector General website. Accessed August 17, 2021. https://oig.hhs.gov/reports-and-publications/workplan/summary/wp-summary-0000577.asp
  9. Global surgery booklet. Centers for Medicare and Medicaid Services website. Updated September 2018. Accessed August 17, 2021. https://www.cms.gov/outreach-and-education/medicare-learning-network-mln/mlnproducts/downloads/globallsurgery-icn907166.pdf
  10. American Medical Association. CPT® Evaluation and management (E/M)—office or other outpatient (99202-99215) and prolonged services (99354, 99355, 99356, 99417) code and guideline changes. Updated March 9, 2021. Accessed August 17, 2021. https://www.ama-assn.org/system/files/2019-06/cpt-office-prolonged-svs-code-changes.pdf
  11. 1997 documentation guidelines for evaluation and management services. Centers for Medicare and Medicaid Services website. Accessed August 17, 2021. https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNEdWebGuide/Downloads/97Docguidelines.pdf
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  • The new 2021 E/M codes actually reduce the hurdles for reporting a separate and distinct E/M service by eliminating the history and physical examination bullet points of the previous code set.
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Increasing Skin of Color Publications in the Dermatology Literature: A Call to Action

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The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.1 Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,2 diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.5 In 2017, Cutis published the inaugural article in its collaboration with the SOCS,6 and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al7 used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.7

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.7 Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.7

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.



The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.7 We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

 

 



Wilson et al7 specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.7 This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.



Both Amuzie et al4 and Wilson et al7 concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.4 High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al8 conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).8 However, Wilson et al7 found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al7 suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.11 We believe that together we will get there one journal article and one citation at a time.

References
  1. Colby SL, Ortman JM. Projections of the size and composition of the U.S. population: 2014 to 2060. United States Census Bureau website. Published March 2015. Accessed August 11, 2021. https://www.census.gov/content/dam/Census/library/publications/2015/demo/p25-1143.pdf
  2. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patient-physician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
  3. Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis. J Am Acad Dermatol. 2021;84:1427-1431. doi:10.1016/j.jaad.2020.06.041
  4. Amuzie AU, Jia JL, Taylor SC, et al. Skin-of-color article representation in dermatology literature 2009-2019: higher citation counts and opportunities for inclusion [published online March 24, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.063
  5. Learn more about SOCS. Skin of Color Society website. Accessed August 11, 2021. https://skinofcolorsociety.org/about-socs/
  6. Subash J, Tull R, McMichael A. Diversity in dermatology: a society devoted to skin of color. Cutis. 2017;99:322-324.
  7. Wilson BN, Sun M, Ashbaugh AG, et al. Assessment of skin of colorand diversity and inclusion content of dermatologic published literature: an analysis and call to action [published online April 20, 2021]. Int J Womens Dermatol. https://doi.org/10.1016/j.ijwd.2021.04.001
  8. Bray JK, McMichael AJ, Huang WW, et al. Publication rates on the topic of racial and ethnic diversity in dermatology versus other specialties. Dermatol Online J. 2020;26:13030/qt094243gp.
  9. Heath CR, Usatine R. Atopic dermatitis. Cutis. 2021;107:332. doi:10.12788/cutis.0274
  10. Heath CR, Usatine R. Psoriasis. Cutis. 2021;108:56. doi:10.12788/cutis.0298
  11. Jones N, Heath CR. Hair at the intersection of dermatology and anthropology: a conversation on race and relationships [published online August 3, 2021]. Pediatr Dermatol. doi:10.1111/pde.14721
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Dr. Heath is from the Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania. Dr. DeLeo is from the Keck School of Medicine at the University of Southern California, Los Angeles. Dr. Taylor is from the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Candrice R. Heath, MD, 3401 N Broad St, 5OPB, Philadelphia, PA 19140 ([email protected]).

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Dr. Heath is from the Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania. Dr. DeLeo is from the Keck School of Medicine at the University of Southern California, Los Angeles. Dr. Taylor is from the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Candrice R. Heath, MD, 3401 N Broad St, 5OPB, Philadelphia, PA 19140 ([email protected]).

Author and Disclosure Information

Dr. Heath is from the Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania. Dr. DeLeo is from the Keck School of Medicine at the University of Southern California, Los Angeles. Dr. Taylor is from the Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Candrice R. Heath, MD, 3401 N Broad St, 5OPB, Philadelphia, PA 19140 ([email protected]).

Article PDF
Article PDF

The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.1 Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,2 diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.5 In 2017, Cutis published the inaugural article in its collaboration with the SOCS,6 and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al7 used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.7

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.7 Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.7

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.



The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.7 We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

 

 



Wilson et al7 specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.7 This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.



Both Amuzie et al4 and Wilson et al7 concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.4 High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al8 conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).8 However, Wilson et al7 found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al7 suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.11 We believe that together we will get there one journal article and one citation at a time.

The US population is becoming more diverse. By 2044, it is predicted that there will be a majority minority population in the United States.1 Therefore, it is imperative to continue to develop educational mechanisms for all dermatologists to increase and maintain competency in skin of color dermatology, which will contribute to the achievement of health equity for patients with all skin tones and hair types.

Not only is clinical skin of color education necessary, but diversity, equity, and inclusion (DEI) education for dermatologists also is critical. Clinical examination,2 diagnosis, and treatment of skin and hair disorders across the skin of color spectrum with cultural humility is essential to achieve health equity. If trainees, dermatologists, other specialists, and primary care clinicians are not frequently exposed to patients with darker skin tones and coily hair, the nuances in diagnosing and treating these patients must be learned in alternate ways.

To ready the nation’s physicians and clinicians to care for the growing diverse population, exposure to more images of dermatologic diseases in those with darker skin tones in journal articles, textbooks, conference lectures, and online dermatology image libraries is necessary to help close the skin of color training and practice gap.3,4 The following initiatives demonstrate how Cutis has sought to address these educational gaps and remains committed to improving DEI education in dermatology.

Collaboration With the Skin of Color Society

The Skin of Color Society (SOCS), which was founded in 2004 by Dr. Susan C. Taylor, is a dermatologic organization with more than 800 members representing 32 countries. Its mission includes promoting awareness and excellence within skin of color dermatology through research, education, and mentorship. The SOCS has utilized strategic partnerships with national and international dermatologists, as well as professional medical organizations and community, industry, and corporate groups, to ultimately ensure that patients with skin of color receive the expert care they deserve.5 In 2017, Cutis published the inaugural article in its collaboration with the SOCS,6 and more articles, which undergo regular peer review, continue to be published quarterly (https://www.mdedge.com/dermatology/skin-color).

Increase Number of Journal Articles on Skin of Color Topics

Increasing the number of journal articles on skin of color–related topics needs to be intentional, as it is a tool that has been identified as a necessary part of enhancing awareness and subsequently improving patient care. Wilson et al7 used stringent criteria to review all articles published from January 2018 to October 2020 in 52 dermatology journals for inclusion of topics on skin of color, hair in patients with skin of color, diversity and inclusion, and socioeconomic and health care disparities in the skin of color population. The journals they reviewed included publications based on continents with majority skin of color populations, such as Asia, as well as those with minority skin of color populations, such as Europe. During the study period, the percentage of articles covering skin of color ranged from 2.04% to 61.8%, with an average of 16.8%.7

The total number of Cutis articles published during the study period was 709, with 132 (18.62%) meeting the investigators’ criteria for articles on skin of color; these included case reports in which at least 1 patient with skin of color was featured.7 Overall, Cutis ranked 16th of the 52 journals for inclusion of skin of color content. Cutis was one of only a few journals based in North America, a non–skin-of-color–predominant continent, to make the top 16 in this study.7

Some of the 132 skin of color articles published in Cutis were the result of the journal’s collaboration with the SOCS. Through this collaboration, articles were published on a variety of skin of color topics, including DEI (6), alopecia and hair care (5), dermoscopy/optical coherence tomography imaging (1), atopic dermatitis (1), cosmetics (1), hidradenitis suppurativa (1), pigmentation (1), rosacea (1), and skin cancer (2). These articles also resulted in a number of podcast discussions (https://www.mdedge.com/podcasts/dermatology-weekly), including one on dealing with DEI, one on pigmentation, and one on dermoscopy/optical coherence tomography imaging. The latter featured the SOCS Scientific Symposium poster winners in 2020.



The number of articles published specifically through Cutis’s collaboration with the SOCS accounted for only a small part of the journal’s 132 skin of color articles identified in the study by Wilson et al.7 We speculate that Cutis’s display of intentional commitment to supporting the inclusion of skin of color articles in the journal may in turn encourage its broader readership to submit more skin of color–focused articles for peer review.

 

 



Wilson et al7 specifically remarked that “Cutis’s [Skin of Color] section in each issue is a promising idea.” They also highlighted Clinics in Dermatology for committing an entire issue to skin of color; however, despite this initiative, Clinics in Dermatology still ranked 35th of 52 journals with regard to the overall percentage of skin of color articles published.7 This suggests that a journal publishing one special issue on skin of color annually is a helpful addition to the literature, but increasing the number of articles related to skin of color in each journal issue, similar to Cutis, will ultimately result in a higher overall number of skin of color articles in the dermatology literature.



Both Amuzie et al4 and Wilson et al7 concluded that the higher a journal’s impact factor, the lower the number of skin of color articles published.However, skin of color articles published in high-impact journals received a higher number of citations than those in other lower-impact journals.4 High-impact journals may use Cutis as a model for increasing the number of skin of color articles they publish, which will have a notable impact on increasing skin of color knowledge and educating dermatologists.

Coverage of Diversity, Equity, and Inclusion

In another study, Bray et al8 conducted a PubMed search of articles indexed for MEDLINE from January 2008 to July 2019 to quantify the number of articles specifically focused on DEI in a variety of medical specialties. The field of dermatology had the highest number of articles published on DEI (25) compared to the other specialties, including family medicine (23), orthopedic surgery (12), internal medicine (9), general surgery (7), radiology (6), ophthalmology (2), and anesthesiology (2).8 However, Wilson et al7 found that, out of all the categories of skin of color articles published in dermatology journals during their study period, those focused on DEI made up less than 1% of the total number of articles. Dermatology is off to a great start compared to other specialties, but there is still more work to do in dermatology for DEI. Cutis’s collaboration with the SOCS has resulted in 6 DEI articles published since 2017.

Think Beyond Dermatology Education

The collaboration between Cutis and the SOCS was established to create a series of articles dedicated to increasing the skin of color dermatology knowledge base of the Cutis readership and beyond; however, increased readership and more citations are needed to amplify the reach of the articles published by these skin of color experts. Cutis’s collaboration with SOCS is one mechanism to increase the skin of color literature, but skin of color and DEI articles outside of this collaboration should continue to be published in each issue of Cutis.

The collaboration between SOCS and Cutis was and continues to be a forward-thinking step toward improving skin of color dermatology education, but there is still work to be done across the medical literature with regard to increasing intentional publication of skin of color articles. Nondermatologist clinicians in the Cutis readership benefit from knowledge of skin of color, as all specialties and primary care will see increased patient diversity in their examination rooms.

To further ensure that primary care is not left behind, Cutis has partnered with The Journal of Family Practice to produce a new column called Dx Across the Skin of Color Spectrum (https://www.mdedge.com/dermatology/dx-across-skin-color-spectrum), which is co-published in both journals.9,10 These one-page fact sheets highlight images of dermatologic conditions in skin of color as well as images of the same condition in lighter skin, a concept suggested by Cutis Associate Editor, Dr. Candrice R. Heath. The goal of this new column is to increase the accurate diagnosis of dermatologic conditions in skin of color and to highlight health disparities related to a particular condition in an easy-to-understand format. Uniquely, Dr. Heath co-authors this content with family physician Dr. Richard P. Usatine.

Final Thoughts

The entire community of medical journals should continue to develop creative ways to educate their readership. Medical professionals stay up-to-date on best practices through journal articles, textbooks, conferences, and even podcasts. Therefore, it is best to incorporate skin of color knowledge throughout all educational programming, particularly through enduring materials such as journal articles. Wilson et al7 suggested that a minimum of 16.8% of a dermatology journal’s articles in each issue should focus on skin of color in addition to special focus issues, as this will work toward more equitable dermatologic care.

Knowledge is only part of the equation; compassionate care with cultural humility is the other part. Publishing scientific facts about biology and structure, diagnosis, and treatment selection in skin of color, as well as committing to lifelong learning about the differences in our patients despite the absence of shared life or cultural experiences, may be the key to truly impacting health equity.11 We believe that together we will get there one journal article and one citation at a time.

References
  1. Colby SL, Ortman JM. Projections of the size and composition of the U.S. population: 2014 to 2060. United States Census Bureau website. Published March 2015. Accessed August 11, 2021. https://www.census.gov/content/dam/Census/library/publications/2015/demo/p25-1143.pdf
  2. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patient-physician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
  3. Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis. J Am Acad Dermatol. 2021;84:1427-1431. doi:10.1016/j.jaad.2020.06.041
  4. Amuzie AU, Jia JL, Taylor SC, et al. Skin-of-color article representation in dermatology literature 2009-2019: higher citation counts and opportunities for inclusion [published online March 24, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.063
  5. Learn more about SOCS. Skin of Color Society website. Accessed August 11, 2021. https://skinofcolorsociety.org/about-socs/
  6. Subash J, Tull R, McMichael A. Diversity in dermatology: a society devoted to skin of color. Cutis. 2017;99:322-324.
  7. Wilson BN, Sun M, Ashbaugh AG, et al. Assessment of skin of colorand diversity and inclusion content of dermatologic published literature: an analysis and call to action [published online April 20, 2021]. Int J Womens Dermatol. https://doi.org/10.1016/j.ijwd.2021.04.001
  8. Bray JK, McMichael AJ, Huang WW, et al. Publication rates on the topic of racial and ethnic diversity in dermatology versus other specialties. Dermatol Online J. 2020;26:13030/qt094243gp.
  9. Heath CR, Usatine R. Atopic dermatitis. Cutis. 2021;107:332. doi:10.12788/cutis.0274
  10. Heath CR, Usatine R. Psoriasis. Cutis. 2021;108:56. doi:10.12788/cutis.0298
  11. Jones N, Heath CR. Hair at the intersection of dermatology and anthropology: a conversation on race and relationships [published online August 3, 2021]. Pediatr Dermatol. doi:10.1111/pde.14721
References
  1. Colby SL, Ortman JM. Projections of the size and composition of the U.S. population: 2014 to 2060. United States Census Bureau website. Published March 2015. Accessed August 11, 2021. https://www.census.gov/content/dam/Census/library/publications/2015/demo/p25-1143.pdf
  2. Grayson C, Heath C. An approach to examining tightly coiled hair among patients with hair loss in race-discordant patient-physician interactions. JAMA Dermatol. 2021;157:505-506. doi:10.1001/jamadermatol.2021.0338
  3. Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis. J Am Acad Dermatol. 2021;84:1427-1431. doi:10.1016/j.jaad.2020.06.041
  4. Amuzie AU, Jia JL, Taylor SC, et al. Skin-of-color article representation in dermatology literature 2009-2019: higher citation counts and opportunities for inclusion [published online March 24, 2021]. J Am Acad Dermatol. doi:10.1016/j.jaad.2021.03.063
  5. Learn more about SOCS. Skin of Color Society website. Accessed August 11, 2021. https://skinofcolorsociety.org/about-socs/
  6. Subash J, Tull R, McMichael A. Diversity in dermatology: a society devoted to skin of color. Cutis. 2017;99:322-324.
  7. Wilson BN, Sun M, Ashbaugh AG, et al. Assessment of skin of colorand diversity and inclusion content of dermatologic published literature: an analysis and call to action [published online April 20, 2021]. Int J Womens Dermatol. https://doi.org/10.1016/j.ijwd.2021.04.001
  8. Bray JK, McMichael AJ, Huang WW, et al. Publication rates on the topic of racial and ethnic diversity in dermatology versus other specialties. Dermatol Online J. 2020;26:13030/qt094243gp.
  9. Heath CR, Usatine R. Atopic dermatitis. Cutis. 2021;107:332. doi:10.12788/cutis.0274
  10. Heath CR, Usatine R. Psoriasis. Cutis. 2021;108:56. doi:10.12788/cutis.0298
  11. Jones N, Heath CR. Hair at the intersection of dermatology and anthropology: a conversation on race and relationships [published online August 3, 2021]. Pediatr Dermatol. doi:10.1111/pde.14721
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  • Submitting more articles related to skin of color for peer review and publication will increase educational opportunities.
  • Journals that publish skin of color articles play a critical role in reducing educational gaps and ultimately help improve patient care for those with skin of color.
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Medical education must takes broader view of disabilities

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“All physicians, regardless of specialty, will work with patients with disabilities,” Corrie Harris, MD, of the University of Louisville (Ky.), said in a plenary session presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Disabilities vary in their visibility, from cognitive and sensory impairments that are not immediately obvious to an obvious physical disability, she said.

One in four adults and one in six children in the United States has a disability, said Dr. Harris. The prevalence of disability increases with age, but occurs across the lifespan, and will likely increase in the future with greater improvements in health care overall.

Dr. Harris reviewed the current conceptual model that forms the basis for the World Health Organization definition of functioning disability. This “functional model” defines disability as caused by interactions between health conditions and the environment, and the response is to “prioritize function to meet patient goals,” Dr. Harris said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

This model is based on collaboration between health care providers and their patients with disabilities, and training is important to help providers make this collaboration successful, said Dr. Harris. Without training, physicians may be ineffective in communicating with patients with disabilities by not speaking directly to the patient, not speaking in a way the patient can understand clearly, and not providing accessible patient education materials. Physicians also tend to minimize the extent of the patient’s expertise in their own condition based on their lived experiences, and tend to underestimate the abilities of patients with disabilities.

However, direct experience with disabled patients and an understanding of the health disparities they endure can help physicians look at these patients “through a more intersectional lens,” that also takes into account social determinants of health, Dr. Harris said. “I have found that people with disabilities are the best teachers about disability, because they have expertise that comes from their lived experience.”
 

Patients are the best teachers

Several initiatives are helping physicians to bridge this gap in understanding and reduce disparities in care. One such program is FRAME: Faces Redefining the Art of Medical Education. FRAME is a web-based film library designed to present medical information to health care providers in training, clinicians, families, and communities in a dignified and humanizing way. FRAME was developed in part by fashion photographer Rick Guidotti, who was inspired after meeting a young woman with albinism to create Positive Exposure, an ongoing project featuring children and adolescents with various disabilities.

FRAME films are “short films presenting all the basic hallmark characteristics of a certain genetic condition, but presented by somebody living with that condition,” said Mr. Guidotti in his presentation during the session.

The National Curriculum Initiative in Developmental Medicine (NCIDM) is designed to incorporate care for individuals with disabilities into medical education. NCIDM is a project created by the American Academy of Developmental Medicine and Dentistry (AADMD).

“The need for this program is that there is no U.S. requirement for medical schools to teach about intellectual and developmental disabilities,” Priya Chandan, MD, also of the University of Louisville, said in her presentation during the session. “Approximately 81% of graduating medical students have no training in caring for adults with disabilities,” said Dr. Chandan, who serves as director of the NCIDM.

The current NCIDM was created as a 5-year partnership between the AADMD and Special Olympics, supported in part by the Centers for Disease Control and Prevention, Dr. Chandan said. The purpose was to provide training to medical students in the field of developmental medicine, meaning the care of individuals with intellectual/developmental disabilities (IDD) across the lifespan. The AADMD has expanded to 26 medical schools in the United States and will reach approximately 4,000 medical students by the conclusion of the current initiative.

One challenge in medical education is getting past the idea that people living with disabilities need to be fixed, said Dr. Chandan. The NCIDM approach reflects Mr. Guidotti’s approach in both the FRAME initiatives and his Positive Exposure foundation, with a focus on treating people as people, and letting individuals with disabilities represent themselves.

Dr. Chandan described the NCIDM curriculum as allowing for flexible teaching methodologies and materials, as long as they meet the NCIDM-created learning goals and objectives. The curriculum also includes standardized evaluations. Each NCIDM program in a participating medical school includes a faculty champion, and the curriculum supports meeting people with IDD not only inside medical settings, but also outside in the community.

NCIDM embraces the idea of community-engaged scholarship, which Dr. Chandan defined as “a form of scholarship that directly benefits the community and is consistent with university and unit missions.” This method combined teaching and conducting research while providing a service to the community.

The next steps for the current NCIDM initiative are to complete collection of data and course evaluations from participating schools by early 2022, followed by continued dissemination and collaboration through AADMD.

Overall, the content of the curriculum explores how and where IDD fits into clinical care, Dr. Chandan said, who also emphasized the implications of communication. “How we think affects how we communicate,” she added. Be mindful of the language used to talk to and about patients with disabilities, both to colleagues and to learners.

When talking to the patient, find something in common, beyond the diagnosis, said Dr. Chandan. Remember that some disabilities are visible and some are not. “Treat people with respect, because you won’t know what their functional level is just by looking,” she concluded.

The presenters had no financial conflicts to disclose.

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“All physicians, regardless of specialty, will work with patients with disabilities,” Corrie Harris, MD, of the University of Louisville (Ky.), said in a plenary session presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Disabilities vary in their visibility, from cognitive and sensory impairments that are not immediately obvious to an obvious physical disability, she said.

One in four adults and one in six children in the United States has a disability, said Dr. Harris. The prevalence of disability increases with age, but occurs across the lifespan, and will likely increase in the future with greater improvements in health care overall.

Dr. Harris reviewed the current conceptual model that forms the basis for the World Health Organization definition of functioning disability. This “functional model” defines disability as caused by interactions between health conditions and the environment, and the response is to “prioritize function to meet patient goals,” Dr. Harris said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

This model is based on collaboration between health care providers and their patients with disabilities, and training is important to help providers make this collaboration successful, said Dr. Harris. Without training, physicians may be ineffective in communicating with patients with disabilities by not speaking directly to the patient, not speaking in a way the patient can understand clearly, and not providing accessible patient education materials. Physicians also tend to minimize the extent of the patient’s expertise in their own condition based on their lived experiences, and tend to underestimate the abilities of patients with disabilities.

However, direct experience with disabled patients and an understanding of the health disparities they endure can help physicians look at these patients “through a more intersectional lens,” that also takes into account social determinants of health, Dr. Harris said. “I have found that people with disabilities are the best teachers about disability, because they have expertise that comes from their lived experience.”
 

Patients are the best teachers

Several initiatives are helping physicians to bridge this gap in understanding and reduce disparities in care. One such program is FRAME: Faces Redefining the Art of Medical Education. FRAME is a web-based film library designed to present medical information to health care providers in training, clinicians, families, and communities in a dignified and humanizing way. FRAME was developed in part by fashion photographer Rick Guidotti, who was inspired after meeting a young woman with albinism to create Positive Exposure, an ongoing project featuring children and adolescents with various disabilities.

FRAME films are “short films presenting all the basic hallmark characteristics of a certain genetic condition, but presented by somebody living with that condition,” said Mr. Guidotti in his presentation during the session.

The National Curriculum Initiative in Developmental Medicine (NCIDM) is designed to incorporate care for individuals with disabilities into medical education. NCIDM is a project created by the American Academy of Developmental Medicine and Dentistry (AADMD).

“The need for this program is that there is no U.S. requirement for medical schools to teach about intellectual and developmental disabilities,” Priya Chandan, MD, also of the University of Louisville, said in her presentation during the session. “Approximately 81% of graduating medical students have no training in caring for adults with disabilities,” said Dr. Chandan, who serves as director of the NCIDM.

The current NCIDM was created as a 5-year partnership between the AADMD and Special Olympics, supported in part by the Centers for Disease Control and Prevention, Dr. Chandan said. The purpose was to provide training to medical students in the field of developmental medicine, meaning the care of individuals with intellectual/developmental disabilities (IDD) across the lifespan. The AADMD has expanded to 26 medical schools in the United States and will reach approximately 4,000 medical students by the conclusion of the current initiative.

One challenge in medical education is getting past the idea that people living with disabilities need to be fixed, said Dr. Chandan. The NCIDM approach reflects Mr. Guidotti’s approach in both the FRAME initiatives and his Positive Exposure foundation, with a focus on treating people as people, and letting individuals with disabilities represent themselves.

Dr. Chandan described the NCIDM curriculum as allowing for flexible teaching methodologies and materials, as long as they meet the NCIDM-created learning goals and objectives. The curriculum also includes standardized evaluations. Each NCIDM program in a participating medical school includes a faculty champion, and the curriculum supports meeting people with IDD not only inside medical settings, but also outside in the community.

NCIDM embraces the idea of community-engaged scholarship, which Dr. Chandan defined as “a form of scholarship that directly benefits the community and is consistent with university and unit missions.” This method combined teaching and conducting research while providing a service to the community.

The next steps for the current NCIDM initiative are to complete collection of data and course evaluations from participating schools by early 2022, followed by continued dissemination and collaboration through AADMD.

Overall, the content of the curriculum explores how and where IDD fits into clinical care, Dr. Chandan said, who also emphasized the implications of communication. “How we think affects how we communicate,” she added. Be mindful of the language used to talk to and about patients with disabilities, both to colleagues and to learners.

When talking to the patient, find something in common, beyond the diagnosis, said Dr. Chandan. Remember that some disabilities are visible and some are not. “Treat people with respect, because you won’t know what their functional level is just by looking,” she concluded.

The presenters had no financial conflicts to disclose.

“All physicians, regardless of specialty, will work with patients with disabilities,” Corrie Harris, MD, of the University of Louisville (Ky.), said in a plenary session presentation at the 2021 virtual Pediatric Hospital Medicine conference.

Disabilities vary in their visibility, from cognitive and sensory impairments that are not immediately obvious to an obvious physical disability, she said.

One in four adults and one in six children in the United States has a disability, said Dr. Harris. The prevalence of disability increases with age, but occurs across the lifespan, and will likely increase in the future with greater improvements in health care overall.

Dr. Harris reviewed the current conceptual model that forms the basis for the World Health Organization definition of functioning disability. This “functional model” defines disability as caused by interactions between health conditions and the environment, and the response is to “prioritize function to meet patient goals,” Dr. Harris said at the meeting, sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

This model is based on collaboration between health care providers and their patients with disabilities, and training is important to help providers make this collaboration successful, said Dr. Harris. Without training, physicians may be ineffective in communicating with patients with disabilities by not speaking directly to the patient, not speaking in a way the patient can understand clearly, and not providing accessible patient education materials. Physicians also tend to minimize the extent of the patient’s expertise in their own condition based on their lived experiences, and tend to underestimate the abilities of patients with disabilities.

However, direct experience with disabled patients and an understanding of the health disparities they endure can help physicians look at these patients “through a more intersectional lens,” that also takes into account social determinants of health, Dr. Harris said. “I have found that people with disabilities are the best teachers about disability, because they have expertise that comes from their lived experience.”
 

Patients are the best teachers

Several initiatives are helping physicians to bridge this gap in understanding and reduce disparities in care. One such program is FRAME: Faces Redefining the Art of Medical Education. FRAME is a web-based film library designed to present medical information to health care providers in training, clinicians, families, and communities in a dignified and humanizing way. FRAME was developed in part by fashion photographer Rick Guidotti, who was inspired after meeting a young woman with albinism to create Positive Exposure, an ongoing project featuring children and adolescents with various disabilities.

FRAME films are “short films presenting all the basic hallmark characteristics of a certain genetic condition, but presented by somebody living with that condition,” said Mr. Guidotti in his presentation during the session.

The National Curriculum Initiative in Developmental Medicine (NCIDM) is designed to incorporate care for individuals with disabilities into medical education. NCIDM is a project created by the American Academy of Developmental Medicine and Dentistry (AADMD).

“The need for this program is that there is no U.S. requirement for medical schools to teach about intellectual and developmental disabilities,” Priya Chandan, MD, also of the University of Louisville, said in her presentation during the session. “Approximately 81% of graduating medical students have no training in caring for adults with disabilities,” said Dr. Chandan, who serves as director of the NCIDM.

The current NCIDM was created as a 5-year partnership between the AADMD and Special Olympics, supported in part by the Centers for Disease Control and Prevention, Dr. Chandan said. The purpose was to provide training to medical students in the field of developmental medicine, meaning the care of individuals with intellectual/developmental disabilities (IDD) across the lifespan. The AADMD has expanded to 26 medical schools in the United States and will reach approximately 4,000 medical students by the conclusion of the current initiative.

One challenge in medical education is getting past the idea that people living with disabilities need to be fixed, said Dr. Chandan. The NCIDM approach reflects Mr. Guidotti’s approach in both the FRAME initiatives and his Positive Exposure foundation, with a focus on treating people as people, and letting individuals with disabilities represent themselves.

Dr. Chandan described the NCIDM curriculum as allowing for flexible teaching methodologies and materials, as long as they meet the NCIDM-created learning goals and objectives. The curriculum also includes standardized evaluations. Each NCIDM program in a participating medical school includes a faculty champion, and the curriculum supports meeting people with IDD not only inside medical settings, but also outside in the community.

NCIDM embraces the idea of community-engaged scholarship, which Dr. Chandan defined as “a form of scholarship that directly benefits the community and is consistent with university and unit missions.” This method combined teaching and conducting research while providing a service to the community.

The next steps for the current NCIDM initiative are to complete collection of data and course evaluations from participating schools by early 2022, followed by continued dissemination and collaboration through AADMD.

Overall, the content of the curriculum explores how and where IDD fits into clinical care, Dr. Chandan said, who also emphasized the implications of communication. “How we think affects how we communicate,” she added. Be mindful of the language used to talk to and about patients with disabilities, both to colleagues and to learners.

When talking to the patient, find something in common, beyond the diagnosis, said Dr. Chandan. Remember that some disabilities are visible and some are not. “Treat people with respect, because you won’t know what their functional level is just by looking,” she concluded.

The presenters had no financial conflicts to disclose.

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A Modified Anchor Taping Technique for Distal Onychocryptosis

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Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.1

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.2

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.3-5 In 2017, Arai and Haneke5 presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

Figure 1. A and B, Distal onychocryptosis of the left first fingernail that occurred 4 months after complete nail avulsion and nail matrix biopsy.

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.3-5 In the Arai and Haneke5 method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.5

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.5

Figure 2. A and B, Modified anchor taping technique for distal onychocryptosis. Strongly adhesive, soft cotton, elastic tape that is 1-inch wide is cut into 2 strips approximately 5-cm long. The strips are applied in succession to the hyponychium, pulled in opposite oblique directions, and secured to opposing sides of the proximal digit.


The patient is instructed on this method in the office and will change the tape at home daily for 2 to 6 weeks, until the nail plate has grown out over the hyponychium (Figure 3). This technique also can be combined with other modalities, such as dilute vinegar soaks performed daily after changing the tape to ease inflammation and prevent infection. Because strongly adhesive tape is used, it also is recommended that the patient soak the tape before removing it to prevent damage to underlying skin.

Figure 3. A and B, Notable improvement in distal onychocryptosis after only 2 weeks of using the modified anchor taping technique daily at home in combination with vinegar soaks.

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.5 We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

References
  1. Geizhals S, Lipner SR. Review of onychocryptosis: epidemiology, pathogenesis, risk factors, diagnosis and treatment. Dermatol Online J. 2019;25:13030/qt9985w2n0
  2. Mayeaux EJ Jr, Carter C, Murphy TE. Ingrown toenail management. Am Fam Physician. 2019;100:158-164.
  3. Tsunoda M, Tsunoda K. Patient-controlled taping for the treatment of ingrown toenails. Ann Fam Med. 2014;12:553-555. doi:10.1370/afm.1712
  4. Watabe A, Yamasaki K, Hashimoto A, et al. Retrospective evaluation of conservative treatment for 140 ingrown toenails with a novel taping procedure. Acta Derm Venereol. 2015;95:822-825. doi:10.2340/00015555-2065
  5. Arai H, Haneke E. Noninvasive treatment for ingrown nails: anchor taping, acrylic affixed gutter splint, sculptured nail, and others. In: Baran R, Hadj-Rabia S, Silverman R, eds. Pediatric Nail Disorders. CRC Press; 2017:252-274.
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Drs. Shahwan and Carr are from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus. Dr. Knackstedt is from the Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

The authors report no conflict of interest.

Correspondence: David R. Carr, MD, MPH, 540 Officenter Pl, Ste 240, Gahanna, OH 43230 ([email protected]).

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Drs. Shahwan and Carr are from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus. Dr. Knackstedt is from the Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

The authors report no conflict of interest.

Correspondence: David R. Carr, MD, MPH, 540 Officenter Pl, Ste 240, Gahanna, OH 43230 ([email protected]).

Author and Disclosure Information

Drs. Shahwan and Carr are from the Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus. Dr. Knackstedt is from the Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

The authors report no conflict of interest.

Correspondence: David R. Carr, MD, MPH, 540 Officenter Pl, Ste 240, Gahanna, OH 43230 ([email protected]).

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Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.1

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.2

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.3-5 In 2017, Arai and Haneke5 presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

Figure 1. A and B, Distal onychocryptosis of the left first fingernail that occurred 4 months after complete nail avulsion and nail matrix biopsy.

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.3-5 In the Arai and Haneke5 method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.5

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.5

Figure 2. A and B, Modified anchor taping technique for distal onychocryptosis. Strongly adhesive, soft cotton, elastic tape that is 1-inch wide is cut into 2 strips approximately 5-cm long. The strips are applied in succession to the hyponychium, pulled in opposite oblique directions, and secured to opposing sides of the proximal digit.


The patient is instructed on this method in the office and will change the tape at home daily for 2 to 6 weeks, until the nail plate has grown out over the hyponychium (Figure 3). This technique also can be combined with other modalities, such as dilute vinegar soaks performed daily after changing the tape to ease inflammation and prevent infection. Because strongly adhesive tape is used, it also is recommended that the patient soak the tape before removing it to prevent damage to underlying skin.

Figure 3. A and B, Notable improvement in distal onychocryptosis after only 2 weeks of using the modified anchor taping technique daily at home in combination with vinegar soaks.

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.5 We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

 

Practice Gap

Onychocryptosis, colloquially known as an ingrown nail, most commonly affects the lateral folds of the toenails. It also can affect the fingernails and the distal aspect of the nail unit, though these presentations are not as well described in the literature. In onychocryptosis, the nail plate grows downward into the periungual skin, resulting in chronic pain and inflammation. Risk factors include overtrimming the nails with rounded edges, local trauma, nail surgery, wearing tight footwear, obesity, and onychomycosis.1

Although surgical intervention might be required for severe or refractory disease, conservative treatment options are first line and often curative. A variety of techniques have been designed to separate the ingrown portion of the nail plate from underlying skin, including placement of an intervening piece of dental floss, cotton, or plastic tubing.2

Anchor taping is another effective method of treating onychocryptosis; a strip of tape is used to gently pull and secure the affected nail fold away from the overlying nail plate. This technique has been well described for the treatment of onychocryptosis of the lateral toenail.3-5 In 2017, Arai and Haneke5 presented a modified technique for the treatment of distal disease.

We present a simplified method that was used successfully in a case of distal onychocryptosis of the thumbnail that occurred approximately 4 months after complete nail avulsion with a nail matrix biopsy (Figure 1).

Figure 1. A and B, Distal onychocryptosis of the left first fingernail that occurred 4 months after complete nail avulsion and nail matrix biopsy.

The Technique

A strongly adhesive, soft cotton, elastic tape that is 1-inch wide, such as Elastikon Elastic Tape (Johnson & Johnson), is used to pull and secure the hyponychium away from the overlying nail plate. When this technique is used for lateral onychocryptosis, a single strip of tape is secured to the affected lateral nail fold, pulled obliquely and proximally, and secured to the base of the digit.3-5 In the Arai and Haneke5 method for the treatment of distal disease, a piece of tape is first placed at the distal nail fold, pulled proximally, and secured to the ventral aspect of the digit. Then, 1 or 2 additional strips of tape are applied to the lateral nail folds, pulled obliquely, and adhered to the base of the digit, as in the classic technique for lateral onychocryptosis.5

In our modification for the treatment of distal disease, only 2 strips of tape are required, each approximately 5-cm long. The first strip of tape is applied to the hyponychium parallel to the long axis of the finger, pulled away from the distal edge of the nail plate, and secured obliquely and proximally to the base of the finger on one side. The second strip of tape is applied to the hyponychium in the same manner, directly overlying the first strip, but is then pulled obliquely in the opposite direction and secured to the other side of the proximal finger (Figure 2). The 2 strips of tape are applied directly overlying each other at the distal nail fold but with opposing tension vectors to optimize pull on the distal nail fold. This modification eliminates the need to apply an initial strip of tape along the long axis of the digit, as described by Arai and Haneke.5

Figure 2. A and B, Modified anchor taping technique for distal onychocryptosis. Strongly adhesive, soft cotton, elastic tape that is 1-inch wide is cut into 2 strips approximately 5-cm long. The strips are applied in succession to the hyponychium, pulled in opposite oblique directions, and secured to opposing sides of the proximal digit.


The patient is instructed on this method in the office and will change the tape at home daily for 2 to 6 weeks, until the nail plate has grown out over the hyponychium (Figure 3). This technique also can be combined with other modalities, such as dilute vinegar soaks performed daily after changing the tape to ease inflammation and prevent infection. Because strongly adhesive tape is used, it also is recommended that the patient soak the tape before removing it to prevent damage to underlying skin.

Figure 3. A and B, Notable improvement in distal onychocryptosis after only 2 weeks of using the modified anchor taping technique daily at home in combination with vinegar soaks.

Practice Implications

Anchor taping is a common and effective treatment of onychocryptosis. Most techniques described in the literature are for lateral toenail cases, which often are managed by podiatry. A modification for the treatment of distal onychocryptosis has been previously described.5 We describe a similar modification using 2 tape strips pulled in opposite directions, which successfully resolved a case of distal onychocryptosis of the fingernail that developed following a nail procedure.

Because nail dystrophy is a relatively common complication of nail surgery, dermatologic surgeons should be aware of this simple, cost-effective, and noninvasive technique for the treatment of distal onychocryptosis.

References
  1. Geizhals S, Lipner SR. Review of onychocryptosis: epidemiology, pathogenesis, risk factors, diagnosis and treatment. Dermatol Online J. 2019;25:13030/qt9985w2n0
  2. Mayeaux EJ Jr, Carter C, Murphy TE. Ingrown toenail management. Am Fam Physician. 2019;100:158-164.
  3. Tsunoda M, Tsunoda K. Patient-controlled taping for the treatment of ingrown toenails. Ann Fam Med. 2014;12:553-555. doi:10.1370/afm.1712
  4. Watabe A, Yamasaki K, Hashimoto A, et al. Retrospective evaluation of conservative treatment for 140 ingrown toenails with a novel taping procedure. Acta Derm Venereol. 2015;95:822-825. doi:10.2340/00015555-2065
  5. Arai H, Haneke E. Noninvasive treatment for ingrown nails: anchor taping, acrylic affixed gutter splint, sculptured nail, and others. In: Baran R, Hadj-Rabia S, Silverman R, eds. Pediatric Nail Disorders. CRC Press; 2017:252-274.
References
  1. Geizhals S, Lipner SR. Review of onychocryptosis: epidemiology, pathogenesis, risk factors, diagnosis and treatment. Dermatol Online J. 2019;25:13030/qt9985w2n0
  2. Mayeaux EJ Jr, Carter C, Murphy TE. Ingrown toenail management. Am Fam Physician. 2019;100:158-164.
  3. Tsunoda M, Tsunoda K. Patient-controlled taping for the treatment of ingrown toenails. Ann Fam Med. 2014;12:553-555. doi:10.1370/afm.1712
  4. Watabe A, Yamasaki K, Hashimoto A, et al. Retrospective evaluation of conservative treatment for 140 ingrown toenails with a novel taping procedure. Acta Derm Venereol. 2015;95:822-825. doi:10.2340/00015555-2065
  5. Arai H, Haneke E. Noninvasive treatment for ingrown nails: anchor taping, acrylic affixed gutter splint, sculptured nail, and others. In: Baran R, Hadj-Rabia S, Silverman R, eds. Pediatric Nail Disorders. CRC Press; 2017:252-274.
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Study finds most adverse events from microneedling are minimal

Article Type
Changed
Thu, 09/09/2021 - 09:50

Most adverse events associated with the practice of microneedling are transient, and most adverse effects and allergic reactions occur in conjunction with combination therapies, according to the results of a systematic review of nearly 3,000 patients.

marcinm111/iStock/Getty Images

Microneedling involves the use of instruments including dermarollers and microneedling pens to cause controlled microtraumas at various skin depths and induce a wounding cascade that ultimately improves the visual appearance of the skin, Sherman Chu, DO, of the department of dermatology at the University of California, Irvine, and colleagues wrote.

Microneedling has increased in popularity because of its relatively low cost, effectiveness, and ease of use, and is often promoted as “a safe alternative treatment, particularly in skin of color, but the safety of microneedling and its complications are not often discussed,” the researchers noted.

In the study, published in Dermatologic Surgery, Dr. Chu and coauthors identified 85 articles for the systematic review of safety data on microneedling. The studies included 30 randomized, controlled trials; 24 prospective studies; 16 case series; 12 case reports; and 3 retrospective cohort studies, with a total of 2,805 patients treated with microneedling.

The devices used in the studies were primarily dermarollers (1,758 procedures), but 425 procedures involved dermapens, and 176 involved unidentified microneedling devices.

The most common adverse effect after microneedling with any device was any of anticipated transient procedural side effects including transient erythema or edema, pain, burning, bruising, pruritus, stinging, bleeding, crusting, and desquamation. Overall, these effects resolved within a week with little or no treatment, the researchers said.

The most commonly reported postprocedure side effects of microneedling were postinflammatory hyperpigmentation (46 incidents), followed by dry skin and exfoliation (41 incidents). Fewer than 15 incidents were reported of each the following: acne flare, pruritus, persistent erythema, herpetic infection, flushing, seborrheic dermatitis, burning, headache, stinging, milia, tram-track scarring, facial allergic granulomatous reaction and systematic hypersensitivity, and tender cervical lymphadenopathy. In addition, one incident each was reported of periorbital dermatitis, phototoxic reaction, pressure urticaria, irritant contact dermatitis, widespread facial inoculation of varicella, pustular folliculitis, and tinea corporis.



The studies suggest that microneedling is generally well tolerated, the researchers wrote. Factors that increased the risk of adverse events included the presence of active infections, darker skin types, metal allergies, and the use of combination therapies. For example, they noted, one randomized, controlled trial showed greater skin irritation in patients treated with both microneedling and tranexamic acid compared with those treated with tranexamic acid alone.

Other studies described increased risk of postinflammatory hyperpigmentation in patients treated with both microneedling and platelet-rich plasma, and with microneedling and topical 5-FU or tacrolimus. Also, in one of the studies in the review, “the development of a delayed granulomatous hypersensitivity reaction in 2 patients was attributed to a reaction to vitamin C serum, whereas another study attributes vitamin A and vitamin C oil to be the cause of a patient’s prolonged erythema and pruritus,” the researchers said.

The study findings were limited to adverse events reported by clinicians in published literature, and did not account for adverse events that occur when microneedling is performed at home or in medical spas. Although the results suggest that microneedling is relatively safe for patients of most skin types, “great caution should be taken when performing microneedling with products not approved to be used intradermally,” they emphasized.

“Further studies are needed to determine which patients are at a higher chance of developing scarring because depth of the needle and skin type do not directly correlate as initially believed,” they concluded.

 

 

Microneedling offers safe alternative to lasers

“Microneedling is a popular procedure that can be used as an alternative to laser treatments to provide low down time, and lower-cost treatments for similar indications in which lasers are used, such as rhytides and scars,” Catherine M. DiGiorgio, MD, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, said in an interview.

Dr. Catherine M. DiGiorgio

“Many clinicians and/or providers utilize microneedling in their practice also because they may not have the ability to perform laser and energy-based device treatments,” noted Dr. DiGiorgio, who was asked to comment on the study findings. “Microneedling is safer than energy-based devices in darker skin types due to the lack of energy or heat being delivered to the epidermis. However, as shown in this study, darker skin types remain at risk for [postinflammatory hyperpigmentation], particularly in the hands of an unskilled, inexperienced operator.”

Dr. DiGiorgio said she was not surprised by the study findings. “Microneedling creates microwounds in the skin, which contributes to the risk of all of the side effects listed in the study. Further, the proper use of microneedling devices by the providers performing the procedure is variable and depths of penetration can vary based on which device or roller pen is used and the experience of the person performing the procedures. Depth, after a certain point, can be inaccurate and can superficially abrade the epidermis rather than the intended individual microneedle punctures.”

Laser and energy-based device treatments can be performed safely in patients with darker skin types in the hands of skilled and experienced laser surgeons, said Dr. DiGiorgio. However, “more studies are needed to determine the effectiveness of microneedling alone compared to other treatment modalities. Patients tend to select microneedling due to affordability and less down time; however, sometimes it may not be the best treatment option for their skin condition.

“Patient education is an important factor because one treatment that worked for one of their friends, for example, may not be the best treatment option for their skin complaints.”

Dr. DiGiorgio added that there are few randomized, controlled trials comparing microneedling to laser treatment. “More studies of this nature would benefit the scientific literature and the addition of histological analysis would help us better understand how these treatments compare on a microscopic level.”

The study received no outside funding and the author has no disclosures. Dr. DiGiorgio has served as a consultant for Allergan Aesthetics.

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Most adverse events associated with the practice of microneedling are transient, and most adverse effects and allergic reactions occur in conjunction with combination therapies, according to the results of a systematic review of nearly 3,000 patients.

marcinm111/iStock/Getty Images

Microneedling involves the use of instruments including dermarollers and microneedling pens to cause controlled microtraumas at various skin depths and induce a wounding cascade that ultimately improves the visual appearance of the skin, Sherman Chu, DO, of the department of dermatology at the University of California, Irvine, and colleagues wrote.

Microneedling has increased in popularity because of its relatively low cost, effectiveness, and ease of use, and is often promoted as “a safe alternative treatment, particularly in skin of color, but the safety of microneedling and its complications are not often discussed,” the researchers noted.

In the study, published in Dermatologic Surgery, Dr. Chu and coauthors identified 85 articles for the systematic review of safety data on microneedling. The studies included 30 randomized, controlled trials; 24 prospective studies; 16 case series; 12 case reports; and 3 retrospective cohort studies, with a total of 2,805 patients treated with microneedling.

The devices used in the studies were primarily dermarollers (1,758 procedures), but 425 procedures involved dermapens, and 176 involved unidentified microneedling devices.

The most common adverse effect after microneedling with any device was any of anticipated transient procedural side effects including transient erythema or edema, pain, burning, bruising, pruritus, stinging, bleeding, crusting, and desquamation. Overall, these effects resolved within a week with little or no treatment, the researchers said.

The most commonly reported postprocedure side effects of microneedling were postinflammatory hyperpigmentation (46 incidents), followed by dry skin and exfoliation (41 incidents). Fewer than 15 incidents were reported of each the following: acne flare, pruritus, persistent erythema, herpetic infection, flushing, seborrheic dermatitis, burning, headache, stinging, milia, tram-track scarring, facial allergic granulomatous reaction and systematic hypersensitivity, and tender cervical lymphadenopathy. In addition, one incident each was reported of periorbital dermatitis, phototoxic reaction, pressure urticaria, irritant contact dermatitis, widespread facial inoculation of varicella, pustular folliculitis, and tinea corporis.



The studies suggest that microneedling is generally well tolerated, the researchers wrote. Factors that increased the risk of adverse events included the presence of active infections, darker skin types, metal allergies, and the use of combination therapies. For example, they noted, one randomized, controlled trial showed greater skin irritation in patients treated with both microneedling and tranexamic acid compared with those treated with tranexamic acid alone.

Other studies described increased risk of postinflammatory hyperpigmentation in patients treated with both microneedling and platelet-rich plasma, and with microneedling and topical 5-FU or tacrolimus. Also, in one of the studies in the review, “the development of a delayed granulomatous hypersensitivity reaction in 2 patients was attributed to a reaction to vitamin C serum, whereas another study attributes vitamin A and vitamin C oil to be the cause of a patient’s prolonged erythema and pruritus,” the researchers said.

The study findings were limited to adverse events reported by clinicians in published literature, and did not account for adverse events that occur when microneedling is performed at home or in medical spas. Although the results suggest that microneedling is relatively safe for patients of most skin types, “great caution should be taken when performing microneedling with products not approved to be used intradermally,” they emphasized.

“Further studies are needed to determine which patients are at a higher chance of developing scarring because depth of the needle and skin type do not directly correlate as initially believed,” they concluded.

 

 

Microneedling offers safe alternative to lasers

“Microneedling is a popular procedure that can be used as an alternative to laser treatments to provide low down time, and lower-cost treatments for similar indications in which lasers are used, such as rhytides and scars,” Catherine M. DiGiorgio, MD, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, said in an interview.

Dr. Catherine M. DiGiorgio

“Many clinicians and/or providers utilize microneedling in their practice also because they may not have the ability to perform laser and energy-based device treatments,” noted Dr. DiGiorgio, who was asked to comment on the study findings. “Microneedling is safer than energy-based devices in darker skin types due to the lack of energy or heat being delivered to the epidermis. However, as shown in this study, darker skin types remain at risk for [postinflammatory hyperpigmentation], particularly in the hands of an unskilled, inexperienced operator.”

Dr. DiGiorgio said she was not surprised by the study findings. “Microneedling creates microwounds in the skin, which contributes to the risk of all of the side effects listed in the study. Further, the proper use of microneedling devices by the providers performing the procedure is variable and depths of penetration can vary based on which device or roller pen is used and the experience of the person performing the procedures. Depth, after a certain point, can be inaccurate and can superficially abrade the epidermis rather than the intended individual microneedle punctures.”

Laser and energy-based device treatments can be performed safely in patients with darker skin types in the hands of skilled and experienced laser surgeons, said Dr. DiGiorgio. However, “more studies are needed to determine the effectiveness of microneedling alone compared to other treatment modalities. Patients tend to select microneedling due to affordability and less down time; however, sometimes it may not be the best treatment option for their skin condition.

“Patient education is an important factor because one treatment that worked for one of their friends, for example, may not be the best treatment option for their skin complaints.”

Dr. DiGiorgio added that there are few randomized, controlled trials comparing microneedling to laser treatment. “More studies of this nature would benefit the scientific literature and the addition of histological analysis would help us better understand how these treatments compare on a microscopic level.”

The study received no outside funding and the author has no disclosures. Dr. DiGiorgio has served as a consultant for Allergan Aesthetics.

Most adverse events associated with the practice of microneedling are transient, and most adverse effects and allergic reactions occur in conjunction with combination therapies, according to the results of a systematic review of nearly 3,000 patients.

marcinm111/iStock/Getty Images

Microneedling involves the use of instruments including dermarollers and microneedling pens to cause controlled microtraumas at various skin depths and induce a wounding cascade that ultimately improves the visual appearance of the skin, Sherman Chu, DO, of the department of dermatology at the University of California, Irvine, and colleagues wrote.

Microneedling has increased in popularity because of its relatively low cost, effectiveness, and ease of use, and is often promoted as “a safe alternative treatment, particularly in skin of color, but the safety of microneedling and its complications are not often discussed,” the researchers noted.

In the study, published in Dermatologic Surgery, Dr. Chu and coauthors identified 85 articles for the systematic review of safety data on microneedling. The studies included 30 randomized, controlled trials; 24 prospective studies; 16 case series; 12 case reports; and 3 retrospective cohort studies, with a total of 2,805 patients treated with microneedling.

The devices used in the studies were primarily dermarollers (1,758 procedures), but 425 procedures involved dermapens, and 176 involved unidentified microneedling devices.

The most common adverse effect after microneedling with any device was any of anticipated transient procedural side effects including transient erythema or edema, pain, burning, bruising, pruritus, stinging, bleeding, crusting, and desquamation. Overall, these effects resolved within a week with little or no treatment, the researchers said.

The most commonly reported postprocedure side effects of microneedling were postinflammatory hyperpigmentation (46 incidents), followed by dry skin and exfoliation (41 incidents). Fewer than 15 incidents were reported of each the following: acne flare, pruritus, persistent erythema, herpetic infection, flushing, seborrheic dermatitis, burning, headache, stinging, milia, tram-track scarring, facial allergic granulomatous reaction and systematic hypersensitivity, and tender cervical lymphadenopathy. In addition, one incident each was reported of periorbital dermatitis, phototoxic reaction, pressure urticaria, irritant contact dermatitis, widespread facial inoculation of varicella, pustular folliculitis, and tinea corporis.



The studies suggest that microneedling is generally well tolerated, the researchers wrote. Factors that increased the risk of adverse events included the presence of active infections, darker skin types, metal allergies, and the use of combination therapies. For example, they noted, one randomized, controlled trial showed greater skin irritation in patients treated with both microneedling and tranexamic acid compared with those treated with tranexamic acid alone.

Other studies described increased risk of postinflammatory hyperpigmentation in patients treated with both microneedling and platelet-rich plasma, and with microneedling and topical 5-FU or tacrolimus. Also, in one of the studies in the review, “the development of a delayed granulomatous hypersensitivity reaction in 2 patients was attributed to a reaction to vitamin C serum, whereas another study attributes vitamin A and vitamin C oil to be the cause of a patient’s prolonged erythema and pruritus,” the researchers said.

The study findings were limited to adverse events reported by clinicians in published literature, and did not account for adverse events that occur when microneedling is performed at home or in medical spas. Although the results suggest that microneedling is relatively safe for patients of most skin types, “great caution should be taken when performing microneedling with products not approved to be used intradermally,” they emphasized.

“Further studies are needed to determine which patients are at a higher chance of developing scarring because depth of the needle and skin type do not directly correlate as initially believed,” they concluded.

 

 

Microneedling offers safe alternative to lasers

“Microneedling is a popular procedure that can be used as an alternative to laser treatments to provide low down time, and lower-cost treatments for similar indications in which lasers are used, such as rhytides and scars,” Catherine M. DiGiorgio, MD, a laser and cosmetic dermatologist at the Boston Center for Facial Rejuvenation, said in an interview.

Dr. Catherine M. DiGiorgio

“Many clinicians and/or providers utilize microneedling in their practice also because they may not have the ability to perform laser and energy-based device treatments,” noted Dr. DiGiorgio, who was asked to comment on the study findings. “Microneedling is safer than energy-based devices in darker skin types due to the lack of energy or heat being delivered to the epidermis. However, as shown in this study, darker skin types remain at risk for [postinflammatory hyperpigmentation], particularly in the hands of an unskilled, inexperienced operator.”

Dr. DiGiorgio said she was not surprised by the study findings. “Microneedling creates microwounds in the skin, which contributes to the risk of all of the side effects listed in the study. Further, the proper use of microneedling devices by the providers performing the procedure is variable and depths of penetration can vary based on which device or roller pen is used and the experience of the person performing the procedures. Depth, after a certain point, can be inaccurate and can superficially abrade the epidermis rather than the intended individual microneedle punctures.”

Laser and energy-based device treatments can be performed safely in patients with darker skin types in the hands of skilled and experienced laser surgeons, said Dr. DiGiorgio. However, “more studies are needed to determine the effectiveness of microneedling alone compared to other treatment modalities. Patients tend to select microneedling due to affordability and less down time; however, sometimes it may not be the best treatment option for their skin condition.

“Patient education is an important factor because one treatment that worked for one of their friends, for example, may not be the best treatment option for their skin complaints.”

Dr. DiGiorgio added that there are few randomized, controlled trials comparing microneedling to laser treatment. “More studies of this nature would benefit the scientific literature and the addition of histological analysis would help us better understand how these treatments compare on a microscopic level.”

The study received no outside funding and the author has no disclosures. Dr. DiGiorgio has served as a consultant for Allergan Aesthetics.

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Hemophagocytic Lymphohistiocytosis: Early Treatment Leading to an Excellent Outcome

Article Type
Changed
Thu, 12/15/2022 - 14:37

HLH is a rare and deadly disease increasingly more present in adults, but following treatment protocol may yield favorable results.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly disease in which unregulated proliferation of histiocytes and T-cell infiltration takes place. It is known as a pediatric disease in which gene defects result in impaired cytotoxic NK- and T-cell function. It has been associated with autosomal recessive inheritance pattern. Without therapy, survival for these patients with active familial HLH is approximately 2 months.

Recognition of the disease has increased over the years, and as a result the diagnosis of HLH in adults also has increased. An acquired form can be triggered by viruses like Epstein-Barr virus, influenza, HIV, lymphoid malignancies, rheumatologic disorders, or immunodeficiency disorders. Survival rates for untreated HLH have been reported at < 5%.1 Despite early recognition and adequate treatment, HLH carries an overall mortality of 50% in the initial presentation, 90% die in the first 8 weeks of treatment due to uncontrolled disease.2

Case Presentation

A 56-year-old man with no active medical issues except for a remote history of non-Hodgkin lymphoma treated with chemotherapy and splenectomy in 1990 presented to the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. He was admitted to the medicine ward due to community acquired pneumonia. Three days into admission his clinical status deteriorated, and the patient was transferred to the intensive care unit (ICU) due to acute respiratory failure and sepsis secondary to worsening pneumonia. Chest imaging demonstrated rapidly progressing diffuse bilateral infiltrates. Due to the severity of the chest imaging, a diagnostic bronchoscopy was performed.

The patient’s antibiotics regimen was empirically escalated to vancomycin 1500 mg IV every 12 hours and meropenem 2 g IV every 8 hours. Despite optimization of therapy, the patient did not show clinical signs of improvement. Febrile episodes persisted, pulmonary infiltrates and hypoxemia worsened, and the patient required a neuromuscular blockade. Since the bronchoscopy was nondiagnostic and deterioration persistent, the differential diagnosis was broadened. This led to the ordering of inflammatory markers. Laboratory testing showed ferritin levels > 16,000 ng/mL, pointing to HLH as a possible diagnosis. Further workup was remarkable for triglycerides of 1234 mg/dL and a fibrinogen of 0.77 g/L. In the setting of bicytopenia and persistent fever, HLH-94 regimen was started with dexamethasone 40 mg daily and etoposide 100 mg/m2. CD25 levels of 154,701 pg/mL were demonstrated as well as a decreased immunoglobulin (Ig) G levels with absent IgM and IgA. Bone marrow biopsy was consistent with hemophagocytosis. The patient eventually was extubated and sent to the oncology ward to continue chemotherapy.

Discussion

A high clinical suspicion is warranted for rapid diagnosis and treatment as HLH evolves in most cases to multiorgan failure and death. The diagnostic criteria for HLH was developed by the Histiocyte Society in 1991 and then restructured in 2004.3,4 In the first diagnostic tool developed in 1991, diagnosis was based on 5 criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). Three additional laboratory findings were also described as part of HLH diagnosis since 2004: low or absent NK-cell-activity, hyperferritinemia of > 500 ng/dL, and high-soluble interleukin-2-receptor levels (CD25) > 2400 U/mL. Overall, 5 of 8 criteria are needed for the HLH diagnosis.

Despite the common use of these diagnostic criteria, they were developed for the pediatric population but have not been validated for adult patients.5 For adult patients, the HScore was developed in 2014. It has 9 variables: 3 are based on clinical findings (known underlying immunosuppression, high temperature, and organomegaly; 5 are based on laboratory values (ferritin, serum glutamic oxaloacetic transaminase, cytopenia, triglycerides, and fibrinogen levels); the last variable uses cytologic findings in the bone marrow. In the initial study, probability of having HLH ranged from < 1% with an HScore of ≤ 90% to > 99% with an HScore of ≥ 250 in noncritically ill adults.5 A recently published retrospective study demonstrated the diagnostic reliability of both the HLH-2004 criteria and HScore in critically ill adult patients. This study concluded that the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria had a 95.0% sensitivity and 93.6% specificity and HScore cutoff of 168 reached a 100% sensitivity and 94.1% specificity.6

 

 



The early negative bronchoscopy lowered the possibility of an infection as the etiology of the clinical presentation and narrowed the hyperferritinemia differential diagnosis. Hyperferritinemia has a sensitivity and specificity of > 90% for diagnosis when above 10,000 ng/dL in the pediatric population.7 This is not the case in adults. Hyperferritinemia is a marker of different inflammatory responses, such as histoplasmosis infection, malignancy, or iron overload rather than an isolated diagnostic tool for HLH.8 It has been reported that CD25 levels less than the diagnostic threshold of 2400 U/mL have a 100% sensitivity for the diagnosis and therefore can rule out the diagnosis. When this is taken into consideration, it can be concluded that CD25 level is a better diagnostic tool when compared with ferritin, but its main limitation is its lack of widespread availability.9 Still, there is a limited number of pathologies that are associated with marked hyperferritinemia, specifically using thresholds of more than 6000 ng/dL.10 Taking into consideration the high mortality of untreated HLH, isolated hyperferritinemia still warrants HLH workup to aggressively pursue the diagnosis and improve outcomes.

The goal of therapy in HLH is prompt inactivation of the dysregulated inflammation with aggressive immunosuppression. In our deteriorating patient, the treatment was started with only 4 of the 8 HLH-2004 diagnostic criteria being met. As per the 2018 Histiocyte Society consensus statement, the decision to start the HLH-94 treatment relies on not only the HLH-2004 diagnostic criteria, but also the patient’s clinical evolution.11 In 1994 the Histiocyte Society also published a treatment protocol termed HLH-94. A Korean retrospective study demonstrated that this protocol led to a 5-year survival rate of 60 to 80% depending on the HLH trigger and response to initial treatment.12 The protocol consists of etoposide at 150 mg/m2, 2 weekly doses in the first 2 weeks and then 1 dose weekly for the next 6 weeks. Dexamethasone is the steroid of choice as it readily crosses the blood-brain barrier. Its dosage consists of 10 mg/m2 for the first 2 weeks and then it is halved every 2 weeks until the eighth week of treatment. A slow taper follows to avoid adrenal insufficiency. Once 8 weeks of treatment have been completed, cyclosporine is added to a goal trough of 200 mcg/dL. If there is central nervous system (CNS) involvement, early aggressive treatment with intrathecal methotrexate is indicated if no improvement is noted during initial therapy.11

In 2004 the Histiocyte Society restructured the HLH-94 treatment protocol with the aim of presenting a more aggressive treatment strategy. The protocol added cyclosporine to the initial induction therapy, rather than later in the ninth week as HLH-94. Neither the use of cyclosporine nor the HLH-2004 have been demonstrated to be superior to the use of etoposide and dexamethasone alone or in the HLH-94 protocol, respectively.13 Cyclosporine is associated with adverse effects (AEs) and may have many contraindications in the acute phase of the disease. Therefore, the HLH-94 protocol is still the recommended regimen.11

To assess adequate clinical response, several clinical and laboratory parameters are followed. Clinically, resolution of fever, improvement in hepatosplenomegaly, lymphadenopathy, and mental status can be useful. Laboratories can be used to assess improvement from organ specific damage such as hepatic involvement or cytopenia. The limitation of these diagnostic studies is that they could falsely suggest an inadequate response to treatment due to concomitant infection or medication AEs. Other markers such as ferritin levels, CD25, and NK cell activity levels are more specific to HLH. Out of them, a decreasing ferritin level has the needed specificity and widespread availability for repeated assessment. On the other hand, both CD25 and NK cell activity are readily available only in specialized centers. An initial high ferritin level is a marker for a poor prognosis, and the rate of decline correlates with mortality. Studies have demonstrated that persistently elevated ferritin levels after treatment initiation are associated with worse outcomes.14,15

Several salvage treatments have been identified in recalcitrant or relapsing disease. In general, chemotherapy needs to be intensified, either by returning to the initial high dosage if recurrence occurs in the weaning phase of treatment or adding other agents if no response was initially achieved. Emapalumab, an interferon γ antibody, was approved by the US Food and Drug Administration for the treatment of intractable HLH after it demonstrated that when added to dexamethasone, it lead to treatment response in 17 out of 27 pediatric patients, with a relatively safe AE profile.16 The goal of intensifying chemotherapy is to have the patient tolerate allogenic stem cell transplant, which is clinically indicated in familial HLH, malignancy induced HLH, and recalcitrant cases. In patients who undergo hematopoietic cell transplantation (HCT) there is a tendency to increase survival to 66% at 5 years.12

Conclusions

HLH is a rare and deadly disease increasingly more present in adults. Our patient who initially presented with a sepsis diagnosis was suspected of having a hematologic etiology for his clinical findings due to markedly elevated ferritin levels. In our patient, the HLH-94 treatment protocol was used, yielding favorable results. Given the lack of specific scientific data backing updated protocols such as HLH-2004 and a comparatively favorable safety profile, current guidelines still recommend using the HLH-94 treatment protocol. Decreasing ferritin levels may be used in conjunction with clinical improvement to demonstrate therapeutic response. Persistence of disease despite standard treatment may warrant novel therapies, such as emapalumab or HCT. Physicians need to be wary of an HLH diagnosis as early identification and treatment may improve its otherwise grim prognosis.

References

1. Chen TY, Hsu MH, Kuo HC, Sheen JM, Cheng MC, Lin YJ. Outcome analysis of pediatric hemophagocytic lymphohistiocytosis. J Formos Med Assoc. 2021;120(1, pt 1):172-179. doi:10.1016/j.jfma.2020.03.025

2. Henter JI, Samuelsson-Horne A, Aricò M, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100(7):2367-2373. doi:10.1182/blood-2002-01-0172

3. Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol. 1991;18(1):29-33.

4. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039

5. Knaak C, Nyvlt P, Schuster FS, et al. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care. 2020;24(1):244. Published 2020 May 24. doi:10.1186/s13054-020-02941-3

6. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;66(9):2613-2620. doi:10.1002/art.38690

7. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618

8. Schaffner M, Rosenstein L, Ballas Z, Suneja M. Significance of Hyperferritinemia in Hospitalized Adults. Am J Med Sci. 2017;354(2):152-158. doi:10.1016/j.amjms.2017.04.016

9. Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017;1(26):2529-2534. Published 2017 Dec 6. doi:10.1182/bloodadvances.2017012310

10. Belfeki N, Strazzulla A, Picque M, Diamantis S. Extreme hyperferritinemia: etiological spectrum and impact on prognosis. Reumatismo. 2020;71(4):199-202. Published 2020 Jan 28. doi:10.4081/reumatismo.2019.1221

11. Ehl S, Astigarraga I, von Bahr Greenwood T, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6(5):1508-1517. doi:10.1016/j.jaip.2018.05.031

12. Yoon JH, Park SS, Jeon YW, et al. Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy. Haematologica. 2019;104(2):269-276. doi:10.3324/haematol.2018.198655

13. Bergsten E, Horne A, Aricó M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728-2738. doi:10.1182/blood-2017-06-788349

14. Lin TF, Ferlic-Stark LL, Allen CE, Kozinetz CA, McClain KL. Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortality. Pediatr Blood Cancer. 2011;56(1):154-155. doi:10.1002/pbc.22774

15. Zhou J, Zhou J, Shen DT, Goyal H, Wu ZQ, Xu HG. Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis. Orphanet J Rare Dis. 2020;15(1):71. Published 2020 Mar 12. doi:10.1186/s13023-020-1336-616. Locatelli F, Jordan MB, Allen CE, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Presented at: American Society of Hematology Annual Meeting, November 29, 2018. Blood. 2018;132(suppl 1):LBA-6. doi:10.1182/blood-2018-120810

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Gerald Marín-García is an Emergency Medicine-Critical Care Attending Physician, and William Rodriguez- Cintrón is Chairperson Pulmonary-Critical Care Department, Pulmonary- Critical Care Fellowship Program Director, both at Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. José María-Rios is Critical Care Fellow at AdventHealth in Orlando, Florida.
Correspondence: William Rodriguez-Cintrón ([email protected])

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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Gerald Marín-García is an Emergency Medicine-Critical Care Attending Physician, and William Rodriguez- Cintrón is Chairperson Pulmonary-Critical Care Department, Pulmonary- Critical Care Fellowship Program Director, both at Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. José María-Rios is Critical Care Fellow at AdventHealth in Orlando, Florida.
Correspondence: William Rodriguez-Cintrón ([email protected])

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Author and Disclosure Information

Gerald Marín-García is an Emergency Medicine-Critical Care Attending Physician, and William Rodriguez- Cintrón is Chairperson Pulmonary-Critical Care Department, Pulmonary- Critical Care Fellowship Program Director, both at Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. José María-Rios is Critical Care Fellow at AdventHealth in Orlando, Florida.
Correspondence: William Rodriguez-Cintrón ([email protected])

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

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HLH is a rare and deadly disease increasingly more present in adults, but following treatment protocol may yield favorable results.

HLH is a rare and deadly disease increasingly more present in adults, but following treatment protocol may yield favorable results.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly disease in which unregulated proliferation of histiocytes and T-cell infiltration takes place. It is known as a pediatric disease in which gene defects result in impaired cytotoxic NK- and T-cell function. It has been associated with autosomal recessive inheritance pattern. Without therapy, survival for these patients with active familial HLH is approximately 2 months.

Recognition of the disease has increased over the years, and as a result the diagnosis of HLH in adults also has increased. An acquired form can be triggered by viruses like Epstein-Barr virus, influenza, HIV, lymphoid malignancies, rheumatologic disorders, or immunodeficiency disorders. Survival rates for untreated HLH have been reported at < 5%.1 Despite early recognition and adequate treatment, HLH carries an overall mortality of 50% in the initial presentation, 90% die in the first 8 weeks of treatment due to uncontrolled disease.2

Case Presentation

A 56-year-old man with no active medical issues except for a remote history of non-Hodgkin lymphoma treated with chemotherapy and splenectomy in 1990 presented to the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. He was admitted to the medicine ward due to community acquired pneumonia. Three days into admission his clinical status deteriorated, and the patient was transferred to the intensive care unit (ICU) due to acute respiratory failure and sepsis secondary to worsening pneumonia. Chest imaging demonstrated rapidly progressing diffuse bilateral infiltrates. Due to the severity of the chest imaging, a diagnostic bronchoscopy was performed.

The patient’s antibiotics regimen was empirically escalated to vancomycin 1500 mg IV every 12 hours and meropenem 2 g IV every 8 hours. Despite optimization of therapy, the patient did not show clinical signs of improvement. Febrile episodes persisted, pulmonary infiltrates and hypoxemia worsened, and the patient required a neuromuscular blockade. Since the bronchoscopy was nondiagnostic and deterioration persistent, the differential diagnosis was broadened. This led to the ordering of inflammatory markers. Laboratory testing showed ferritin levels > 16,000 ng/mL, pointing to HLH as a possible diagnosis. Further workup was remarkable for triglycerides of 1234 mg/dL and a fibrinogen of 0.77 g/L. In the setting of bicytopenia and persistent fever, HLH-94 regimen was started with dexamethasone 40 mg daily and etoposide 100 mg/m2. CD25 levels of 154,701 pg/mL were demonstrated as well as a decreased immunoglobulin (Ig) G levels with absent IgM and IgA. Bone marrow biopsy was consistent with hemophagocytosis. The patient eventually was extubated and sent to the oncology ward to continue chemotherapy.

Discussion

A high clinical suspicion is warranted for rapid diagnosis and treatment as HLH evolves in most cases to multiorgan failure and death. The diagnostic criteria for HLH was developed by the Histiocyte Society in 1991 and then restructured in 2004.3,4 In the first diagnostic tool developed in 1991, diagnosis was based on 5 criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). Three additional laboratory findings were also described as part of HLH diagnosis since 2004: low or absent NK-cell-activity, hyperferritinemia of > 500 ng/dL, and high-soluble interleukin-2-receptor levels (CD25) > 2400 U/mL. Overall, 5 of 8 criteria are needed for the HLH diagnosis.

Despite the common use of these diagnostic criteria, they were developed for the pediatric population but have not been validated for adult patients.5 For adult patients, the HScore was developed in 2014. It has 9 variables: 3 are based on clinical findings (known underlying immunosuppression, high temperature, and organomegaly; 5 are based on laboratory values (ferritin, serum glutamic oxaloacetic transaminase, cytopenia, triglycerides, and fibrinogen levels); the last variable uses cytologic findings in the bone marrow. In the initial study, probability of having HLH ranged from < 1% with an HScore of ≤ 90% to > 99% with an HScore of ≥ 250 in noncritically ill adults.5 A recently published retrospective study demonstrated the diagnostic reliability of both the HLH-2004 criteria and HScore in critically ill adult patients. This study concluded that the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria had a 95.0% sensitivity and 93.6% specificity and HScore cutoff of 168 reached a 100% sensitivity and 94.1% specificity.6

 

 



The early negative bronchoscopy lowered the possibility of an infection as the etiology of the clinical presentation and narrowed the hyperferritinemia differential diagnosis. Hyperferritinemia has a sensitivity and specificity of > 90% for diagnosis when above 10,000 ng/dL in the pediatric population.7 This is not the case in adults. Hyperferritinemia is a marker of different inflammatory responses, such as histoplasmosis infection, malignancy, or iron overload rather than an isolated diagnostic tool for HLH.8 It has been reported that CD25 levels less than the diagnostic threshold of 2400 U/mL have a 100% sensitivity for the diagnosis and therefore can rule out the diagnosis. When this is taken into consideration, it can be concluded that CD25 level is a better diagnostic tool when compared with ferritin, but its main limitation is its lack of widespread availability.9 Still, there is a limited number of pathologies that are associated with marked hyperferritinemia, specifically using thresholds of more than 6000 ng/dL.10 Taking into consideration the high mortality of untreated HLH, isolated hyperferritinemia still warrants HLH workup to aggressively pursue the diagnosis and improve outcomes.

The goal of therapy in HLH is prompt inactivation of the dysregulated inflammation with aggressive immunosuppression. In our deteriorating patient, the treatment was started with only 4 of the 8 HLH-2004 diagnostic criteria being met. As per the 2018 Histiocyte Society consensus statement, the decision to start the HLH-94 treatment relies on not only the HLH-2004 diagnostic criteria, but also the patient’s clinical evolution.11 In 1994 the Histiocyte Society also published a treatment protocol termed HLH-94. A Korean retrospective study demonstrated that this protocol led to a 5-year survival rate of 60 to 80% depending on the HLH trigger and response to initial treatment.12 The protocol consists of etoposide at 150 mg/m2, 2 weekly doses in the first 2 weeks and then 1 dose weekly for the next 6 weeks. Dexamethasone is the steroid of choice as it readily crosses the blood-brain barrier. Its dosage consists of 10 mg/m2 for the first 2 weeks and then it is halved every 2 weeks until the eighth week of treatment. A slow taper follows to avoid adrenal insufficiency. Once 8 weeks of treatment have been completed, cyclosporine is added to a goal trough of 200 mcg/dL. If there is central nervous system (CNS) involvement, early aggressive treatment with intrathecal methotrexate is indicated if no improvement is noted during initial therapy.11

In 2004 the Histiocyte Society restructured the HLH-94 treatment protocol with the aim of presenting a more aggressive treatment strategy. The protocol added cyclosporine to the initial induction therapy, rather than later in the ninth week as HLH-94. Neither the use of cyclosporine nor the HLH-2004 have been demonstrated to be superior to the use of etoposide and dexamethasone alone or in the HLH-94 protocol, respectively.13 Cyclosporine is associated with adverse effects (AEs) and may have many contraindications in the acute phase of the disease. Therefore, the HLH-94 protocol is still the recommended regimen.11

To assess adequate clinical response, several clinical and laboratory parameters are followed. Clinically, resolution of fever, improvement in hepatosplenomegaly, lymphadenopathy, and mental status can be useful. Laboratories can be used to assess improvement from organ specific damage such as hepatic involvement or cytopenia. The limitation of these diagnostic studies is that they could falsely suggest an inadequate response to treatment due to concomitant infection or medication AEs. Other markers such as ferritin levels, CD25, and NK cell activity levels are more specific to HLH. Out of them, a decreasing ferritin level has the needed specificity and widespread availability for repeated assessment. On the other hand, both CD25 and NK cell activity are readily available only in specialized centers. An initial high ferritin level is a marker for a poor prognosis, and the rate of decline correlates with mortality. Studies have demonstrated that persistently elevated ferritin levels after treatment initiation are associated with worse outcomes.14,15

Several salvage treatments have been identified in recalcitrant or relapsing disease. In general, chemotherapy needs to be intensified, either by returning to the initial high dosage if recurrence occurs in the weaning phase of treatment or adding other agents if no response was initially achieved. Emapalumab, an interferon γ antibody, was approved by the US Food and Drug Administration for the treatment of intractable HLH after it demonstrated that when added to dexamethasone, it lead to treatment response in 17 out of 27 pediatric patients, with a relatively safe AE profile.16 The goal of intensifying chemotherapy is to have the patient tolerate allogenic stem cell transplant, which is clinically indicated in familial HLH, malignancy induced HLH, and recalcitrant cases. In patients who undergo hematopoietic cell transplantation (HCT) there is a tendency to increase survival to 66% at 5 years.12

Conclusions

HLH is a rare and deadly disease increasingly more present in adults. Our patient who initially presented with a sepsis diagnosis was suspected of having a hematologic etiology for his clinical findings due to markedly elevated ferritin levels. In our patient, the HLH-94 treatment protocol was used, yielding favorable results. Given the lack of specific scientific data backing updated protocols such as HLH-2004 and a comparatively favorable safety profile, current guidelines still recommend using the HLH-94 treatment protocol. Decreasing ferritin levels may be used in conjunction with clinical improvement to demonstrate therapeutic response. Persistence of disease despite standard treatment may warrant novel therapies, such as emapalumab or HCT. Physicians need to be wary of an HLH diagnosis as early identification and treatment may improve its otherwise grim prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and deadly disease in which unregulated proliferation of histiocytes and T-cell infiltration takes place. It is known as a pediatric disease in which gene defects result in impaired cytotoxic NK- and T-cell function. It has been associated with autosomal recessive inheritance pattern. Without therapy, survival for these patients with active familial HLH is approximately 2 months.

Recognition of the disease has increased over the years, and as a result the diagnosis of HLH in adults also has increased. An acquired form can be triggered by viruses like Epstein-Barr virus, influenza, HIV, lymphoid malignancies, rheumatologic disorders, or immunodeficiency disorders. Survival rates for untreated HLH have been reported at < 5%.1 Despite early recognition and adequate treatment, HLH carries an overall mortality of 50% in the initial presentation, 90% die in the first 8 weeks of treatment due to uncontrolled disease.2

Case Presentation

A 56-year-old man with no active medical issues except for a remote history of non-Hodgkin lymphoma treated with chemotherapy and splenectomy in 1990 presented to the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico. He was admitted to the medicine ward due to community acquired pneumonia. Three days into admission his clinical status deteriorated, and the patient was transferred to the intensive care unit (ICU) due to acute respiratory failure and sepsis secondary to worsening pneumonia. Chest imaging demonstrated rapidly progressing diffuse bilateral infiltrates. Due to the severity of the chest imaging, a diagnostic bronchoscopy was performed.

The patient’s antibiotics regimen was empirically escalated to vancomycin 1500 mg IV every 12 hours and meropenem 2 g IV every 8 hours. Despite optimization of therapy, the patient did not show clinical signs of improvement. Febrile episodes persisted, pulmonary infiltrates and hypoxemia worsened, and the patient required a neuromuscular blockade. Since the bronchoscopy was nondiagnostic and deterioration persistent, the differential diagnosis was broadened. This led to the ordering of inflammatory markers. Laboratory testing showed ferritin levels > 16,000 ng/mL, pointing to HLH as a possible diagnosis. Further workup was remarkable for triglycerides of 1234 mg/dL and a fibrinogen of 0.77 g/L. In the setting of bicytopenia and persistent fever, HLH-94 regimen was started with dexamethasone 40 mg daily and etoposide 100 mg/m2. CD25 levels of 154,701 pg/mL were demonstrated as well as a decreased immunoglobulin (Ig) G levels with absent IgM and IgA. Bone marrow biopsy was consistent with hemophagocytosis. The patient eventually was extubated and sent to the oncology ward to continue chemotherapy.

Discussion

A high clinical suspicion is warranted for rapid diagnosis and treatment as HLH evolves in most cases to multiorgan failure and death. The diagnostic criteria for HLH was developed by the Histiocyte Society in 1991 and then restructured in 2004.3,4 In the first diagnostic tool developed in 1991, diagnosis was based on 5 criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). Three additional laboratory findings were also described as part of HLH diagnosis since 2004: low or absent NK-cell-activity, hyperferritinemia of > 500 ng/dL, and high-soluble interleukin-2-receptor levels (CD25) > 2400 U/mL. Overall, 5 of 8 criteria are needed for the HLH diagnosis.

Despite the common use of these diagnostic criteria, they were developed for the pediatric population but have not been validated for adult patients.5 For adult patients, the HScore was developed in 2014. It has 9 variables: 3 are based on clinical findings (known underlying immunosuppression, high temperature, and organomegaly; 5 are based on laboratory values (ferritin, serum glutamic oxaloacetic transaminase, cytopenia, triglycerides, and fibrinogen levels); the last variable uses cytologic findings in the bone marrow. In the initial study, probability of having HLH ranged from < 1% with an HScore of ≤ 90% to > 99% with an HScore of ≥ 250 in noncritically ill adults.5 A recently published retrospective study demonstrated the diagnostic reliability of both the HLH-2004 criteria and HScore in critically ill adult patients. This study concluded that the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria had a 95.0% sensitivity and 93.6% specificity and HScore cutoff of 168 reached a 100% sensitivity and 94.1% specificity.6

 

 



The early negative bronchoscopy lowered the possibility of an infection as the etiology of the clinical presentation and narrowed the hyperferritinemia differential diagnosis. Hyperferritinemia has a sensitivity and specificity of > 90% for diagnosis when above 10,000 ng/dL in the pediatric population.7 This is not the case in adults. Hyperferritinemia is a marker of different inflammatory responses, such as histoplasmosis infection, malignancy, or iron overload rather than an isolated diagnostic tool for HLH.8 It has been reported that CD25 levels less than the diagnostic threshold of 2400 U/mL have a 100% sensitivity for the diagnosis and therefore can rule out the diagnosis. When this is taken into consideration, it can be concluded that CD25 level is a better diagnostic tool when compared with ferritin, but its main limitation is its lack of widespread availability.9 Still, there is a limited number of pathologies that are associated with marked hyperferritinemia, specifically using thresholds of more than 6000 ng/dL.10 Taking into consideration the high mortality of untreated HLH, isolated hyperferritinemia still warrants HLH workup to aggressively pursue the diagnosis and improve outcomes.

The goal of therapy in HLH is prompt inactivation of the dysregulated inflammation with aggressive immunosuppression. In our deteriorating patient, the treatment was started with only 4 of the 8 HLH-2004 diagnostic criteria being met. As per the 2018 Histiocyte Society consensus statement, the decision to start the HLH-94 treatment relies on not only the HLH-2004 diagnostic criteria, but also the patient’s clinical evolution.11 In 1994 the Histiocyte Society also published a treatment protocol termed HLH-94. A Korean retrospective study demonstrated that this protocol led to a 5-year survival rate of 60 to 80% depending on the HLH trigger and response to initial treatment.12 The protocol consists of etoposide at 150 mg/m2, 2 weekly doses in the first 2 weeks and then 1 dose weekly for the next 6 weeks. Dexamethasone is the steroid of choice as it readily crosses the blood-brain barrier. Its dosage consists of 10 mg/m2 for the first 2 weeks and then it is halved every 2 weeks until the eighth week of treatment. A slow taper follows to avoid adrenal insufficiency. Once 8 weeks of treatment have been completed, cyclosporine is added to a goal trough of 200 mcg/dL. If there is central nervous system (CNS) involvement, early aggressive treatment with intrathecal methotrexate is indicated if no improvement is noted during initial therapy.11

In 2004 the Histiocyte Society restructured the HLH-94 treatment protocol with the aim of presenting a more aggressive treatment strategy. The protocol added cyclosporine to the initial induction therapy, rather than later in the ninth week as HLH-94. Neither the use of cyclosporine nor the HLH-2004 have been demonstrated to be superior to the use of etoposide and dexamethasone alone or in the HLH-94 protocol, respectively.13 Cyclosporine is associated with adverse effects (AEs) and may have many contraindications in the acute phase of the disease. Therefore, the HLH-94 protocol is still the recommended regimen.11

To assess adequate clinical response, several clinical and laboratory parameters are followed. Clinically, resolution of fever, improvement in hepatosplenomegaly, lymphadenopathy, and mental status can be useful. Laboratories can be used to assess improvement from organ specific damage such as hepatic involvement or cytopenia. The limitation of these diagnostic studies is that they could falsely suggest an inadequate response to treatment due to concomitant infection or medication AEs. Other markers such as ferritin levels, CD25, and NK cell activity levels are more specific to HLH. Out of them, a decreasing ferritin level has the needed specificity and widespread availability for repeated assessment. On the other hand, both CD25 and NK cell activity are readily available only in specialized centers. An initial high ferritin level is a marker for a poor prognosis, and the rate of decline correlates with mortality. Studies have demonstrated that persistently elevated ferritin levels after treatment initiation are associated with worse outcomes.14,15

Several salvage treatments have been identified in recalcitrant or relapsing disease. In general, chemotherapy needs to be intensified, either by returning to the initial high dosage if recurrence occurs in the weaning phase of treatment or adding other agents if no response was initially achieved. Emapalumab, an interferon γ antibody, was approved by the US Food and Drug Administration for the treatment of intractable HLH after it demonstrated that when added to dexamethasone, it lead to treatment response in 17 out of 27 pediatric patients, with a relatively safe AE profile.16 The goal of intensifying chemotherapy is to have the patient tolerate allogenic stem cell transplant, which is clinically indicated in familial HLH, malignancy induced HLH, and recalcitrant cases. In patients who undergo hematopoietic cell transplantation (HCT) there is a tendency to increase survival to 66% at 5 years.12

Conclusions

HLH is a rare and deadly disease increasingly more present in adults. Our patient who initially presented with a sepsis diagnosis was suspected of having a hematologic etiology for his clinical findings due to markedly elevated ferritin levels. In our patient, the HLH-94 treatment protocol was used, yielding favorable results. Given the lack of specific scientific data backing updated protocols such as HLH-2004 and a comparatively favorable safety profile, current guidelines still recommend using the HLH-94 treatment protocol. Decreasing ferritin levels may be used in conjunction with clinical improvement to demonstrate therapeutic response. Persistence of disease despite standard treatment may warrant novel therapies, such as emapalumab or HCT. Physicians need to be wary of an HLH diagnosis as early identification and treatment may improve its otherwise grim prognosis.

References

1. Chen TY, Hsu MH, Kuo HC, Sheen JM, Cheng MC, Lin YJ. Outcome analysis of pediatric hemophagocytic lymphohistiocytosis. J Formos Med Assoc. 2021;120(1, pt 1):172-179. doi:10.1016/j.jfma.2020.03.025

2. Henter JI, Samuelsson-Horne A, Aricò M, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100(7):2367-2373. doi:10.1182/blood-2002-01-0172

3. Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol. 1991;18(1):29-33.

4. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039

5. Knaak C, Nyvlt P, Schuster FS, et al. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care. 2020;24(1):244. Published 2020 May 24. doi:10.1186/s13054-020-02941-3

6. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;66(9):2613-2620. doi:10.1002/art.38690

7. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618

8. Schaffner M, Rosenstein L, Ballas Z, Suneja M. Significance of Hyperferritinemia in Hospitalized Adults. Am J Med Sci. 2017;354(2):152-158. doi:10.1016/j.amjms.2017.04.016

9. Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017;1(26):2529-2534. Published 2017 Dec 6. doi:10.1182/bloodadvances.2017012310

10. Belfeki N, Strazzulla A, Picque M, Diamantis S. Extreme hyperferritinemia: etiological spectrum and impact on prognosis. Reumatismo. 2020;71(4):199-202. Published 2020 Jan 28. doi:10.4081/reumatismo.2019.1221

11. Ehl S, Astigarraga I, von Bahr Greenwood T, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6(5):1508-1517. doi:10.1016/j.jaip.2018.05.031

12. Yoon JH, Park SS, Jeon YW, et al. Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy. Haematologica. 2019;104(2):269-276. doi:10.3324/haematol.2018.198655

13. Bergsten E, Horne A, Aricó M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728-2738. doi:10.1182/blood-2017-06-788349

14. Lin TF, Ferlic-Stark LL, Allen CE, Kozinetz CA, McClain KL. Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortality. Pediatr Blood Cancer. 2011;56(1):154-155. doi:10.1002/pbc.22774

15. Zhou J, Zhou J, Shen DT, Goyal H, Wu ZQ, Xu HG. Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis. Orphanet J Rare Dis. 2020;15(1):71. Published 2020 Mar 12. doi:10.1186/s13023-020-1336-616. Locatelli F, Jordan MB, Allen CE, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Presented at: American Society of Hematology Annual Meeting, November 29, 2018. Blood. 2018;132(suppl 1):LBA-6. doi:10.1182/blood-2018-120810

References

1. Chen TY, Hsu MH, Kuo HC, Sheen JM, Cheng MC, Lin YJ. Outcome analysis of pediatric hemophagocytic lymphohistiocytosis. J Formos Med Assoc. 2021;120(1, pt 1):172-179. doi:10.1016/j.jfma.2020.03.025

2. Henter JI, Samuelsson-Horne A, Aricò M, et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 2002;100(7):2367-2373. doi:10.1182/blood-2002-01-0172

3. Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol. 1991;18(1):29-33.

4. Henter JI, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-131. doi:10.1002/pbc.21039

5. Knaak C, Nyvlt P, Schuster FS, et al. Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore. Crit Care. 2020;24(1):244. Published 2020 May 24. doi:10.1186/s13054-020-02941-3

6. Fardet L, Galicier L, Lambotte O, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014;66(9):2613-2620. doi:10.1002/art.38690

7. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618

8. Schaffner M, Rosenstein L, Ballas Z, Suneja M. Significance of Hyperferritinemia in Hospitalized Adults. Am J Med Sci. 2017;354(2):152-158. doi:10.1016/j.amjms.2017.04.016

9. Hayden A, Lin M, Park S, et al. Soluble interleukin-2 receptor is a sensitive diagnostic test in adult HLH. Blood Adv. 2017;1(26):2529-2534. Published 2017 Dec 6. doi:10.1182/bloodadvances.2017012310

10. Belfeki N, Strazzulla A, Picque M, Diamantis S. Extreme hyperferritinemia: etiological spectrum and impact on prognosis. Reumatismo. 2020;71(4):199-202. Published 2020 Jan 28. doi:10.4081/reumatismo.2019.1221

11. Ehl S, Astigarraga I, von Bahr Greenwood T, et al. Recommendations for the use of etoposide-based therapy and bone marrow transplantation for the treatment of HLH: consensus statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6(5):1508-1517. doi:10.1016/j.jaip.2018.05.031

12. Yoon JH, Park SS, Jeon YW, et al. Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy. Haematologica. 2019;104(2):269-276. doi:10.3324/haematol.2018.198655

13. Bergsten E, Horne A, Aricó M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130(25):2728-2738. doi:10.1182/blood-2017-06-788349

14. Lin TF, Ferlic-Stark LL, Allen CE, Kozinetz CA, McClain KL. Rate of decline of ferritin in patients with hemophagocytic lymphohistiocytosis as a prognostic variable for mortality. Pediatr Blood Cancer. 2011;56(1):154-155. doi:10.1002/pbc.22774

15. Zhou J, Zhou J, Shen DT, Goyal H, Wu ZQ, Xu HG. Development and validation of the prognostic value of ferritin in adult patients with Hemophagocytic Lymphohistiocytosis. Orphanet J Rare Dis. 2020;15(1):71. Published 2020 Mar 12. doi:10.1186/s13023-020-1336-616. Locatelli F, Jordan MB, Allen CE, et al. Safety and efficacy of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis. Presented at: American Society of Hematology Annual Meeting, November 29, 2018. Blood. 2018;132(suppl 1):LBA-6. doi:10.1182/blood-2018-120810

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Genetic shift increases susceptibility to childhood ALL

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Thu, 09/09/2021 - 09:15

A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.

Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.

The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.

Lymphocyte risk

The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).

Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).

The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).

“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.

They reported that they had no competing interests.

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A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.

Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.

The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.

Lymphocyte risk

The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).

Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).

The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).

“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.

They reported that they had no competing interests.

A genetically induced shift toward higher lymphocyte counts was found to increase susceptibility to childhood acute lymphoblastic leukemia, according to the results of a large genome-wide association study of 2,666 childhood patients with ALL as compared with 60,272 control individuals.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the department of epidemiology and biostatistics, University of California, San Francisco, and colleagues.

The development of ALL is thought to follow a two-hit model of leukemogenesis; in utero formation of a preleukemic clone and subsequent postnatal acquisition of secondary somatic mutations that leads to overt leukemia, according to Linda Kachuri, PhD, of the Department of Epidemiology and Biostatistics, University of California San Francisco, and colleagues.

Previous research has shown that several childhood-ALL–risk regions have also been associated with variation in blood-cell traits and a recent phenome-wide association study of childhood ALL identified platelet count as the most enriched trait among known ALL-risk loci. To further explore this issue, the researchers conducted their comprehensive study of the role of blood-cell-trait variation in the etiology of childhood ALL.

The researchers identified 3,000 blood-cell-trait–associated variants, which accounted for 4.0% to 23.9% of trait variation and included 115 loci associated with blood-cell ratios: lymphocyte-to-monocyte ratio (LMR); neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ratio (PLR), according to a report published online in The American Journal of Human Genetics.

Lymphocyte risk

The researchers found that ALL susceptibility was genetically correlated with lymphocyte counts (rg = 0.088, P = .0004) and PLR (rg = 0.072, P = .0017).

Using Mendelian randomization analyses, a genetically predicted increase in lymphocyte counts was found to be associated with increased ALL risk (odds ratio [OR] = 1.16, P = .031). This correlation was strengthened after the researchers accounted for other cell types (OR = 1.43, P = .0009).

The researchers observed positive associations with increasing LMR (OR = 1.22, P = .0017) as well as inverse effects for NLR (OR = 0.67, P = .0003) and PLR (OR = 0.80, P = .002).

“We identified the cell-type ratios LMR, NLR, and PLR as independent risk factors for ALL and found evidence that these ratios have distinct genetic mechanisms that are not captured by their component traits. In multivariable MR analyses that concurrently modeled the effects of lymphocyte, monocyte, neutrophil, and platelet counts on ALL, lymphocytes remained as the only independent risk factor and this association with ALL strengthened compared to univariate analyses,” the researchers stated.

They reported that they had no competing interests.

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FROM THE AMERICAN JOURNAL OF HUMAN GENETICS

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Facial eruptions

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Changed
Thu, 09/16/2021 - 09:07
Display Headline
Facial eruptions

This was a vigorous response to the 5-FU treatment and was actually within the range of expected outcomes for a patient with a heavy burden of AKs. The erythema and superficial skin flaking spared areas unaffected by pre-cancers.

AKs manifest as rough, pink to brown macules or papules on sun-damaged skin and represent a precancerous change in keratinocytes that can lead to invasive squamous cell carcinoma. For this reason, AKs are often treated when they are observed. When targeting an entire “field” of AKs, a gold standard therapy is topical 5-FU. Prescribing 5-FU is safe and effective, but requires patient education, therapy customization, and anticipatory guidance.

Compared with other field treatments (eg, photodynamic therapy, topical diclofenac, imiquimod), 5-FU is the most successful and cost effective; it is first-line therapy and has the longest track record.1,2 5-FU represses DNA synthesis. It’s helpful to describe 5-FU to patients as “fake DNA” that targets precancerous cells that are dividing rapidly. But a word of caution: Patients should be advised, in advance, to avoid significant sun exposure while using 5-FU, as the drug will lose its targeted effect and cause more generalized skin damage.

Physicians can modulate the severity of the response to 5-FU by decreasing the frequency or length of therapy by using a weaker (and more expensive) once daily 0.5% long-acting formulation. Additionally, to improve comfort, low-potency topical steroids such as hydrocortisone ointment 0.5% to 2.5% can be applied after completion of therapy to speed up the healing process. These adjustments improve tolerance of therapy, but the precise effect on efficacy is unknown.

Because of the degree of redness and erythema that developed in this patient, treatment was stopped a week early. There was also concern about possible bacterial involvement in the heavy skin sloughing, so the patient was given topical mupirocin ointment to apply TID for 7 days. Her skin cleared after 3 weeks and all previous AKs were clinically eliminated.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Gupta AK, Paquet M. Network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169:250-259. doi: 10.1111/bjd.12343

2. Jansen MHE, Kessels JPHM, Merks I, et al. A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands. Br J Dermatol. 2020;183:738-744. doi: 10.1111/bjd.18884

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This was a vigorous response to the 5-FU treatment and was actually within the range of expected outcomes for a patient with a heavy burden of AKs. The erythema and superficial skin flaking spared areas unaffected by pre-cancers.

AKs manifest as rough, pink to brown macules or papules on sun-damaged skin and represent a precancerous change in keratinocytes that can lead to invasive squamous cell carcinoma. For this reason, AKs are often treated when they are observed. When targeting an entire “field” of AKs, a gold standard therapy is topical 5-FU. Prescribing 5-FU is safe and effective, but requires patient education, therapy customization, and anticipatory guidance.

Compared with other field treatments (eg, photodynamic therapy, topical diclofenac, imiquimod), 5-FU is the most successful and cost effective; it is first-line therapy and has the longest track record.1,2 5-FU represses DNA synthesis. It’s helpful to describe 5-FU to patients as “fake DNA” that targets precancerous cells that are dividing rapidly. But a word of caution: Patients should be advised, in advance, to avoid significant sun exposure while using 5-FU, as the drug will lose its targeted effect and cause more generalized skin damage.

Physicians can modulate the severity of the response to 5-FU by decreasing the frequency or length of therapy by using a weaker (and more expensive) once daily 0.5% long-acting formulation. Additionally, to improve comfort, low-potency topical steroids such as hydrocortisone ointment 0.5% to 2.5% can be applied after completion of therapy to speed up the healing process. These adjustments improve tolerance of therapy, but the precise effect on efficacy is unknown.

Because of the degree of redness and erythema that developed in this patient, treatment was stopped a week early. There was also concern about possible bacterial involvement in the heavy skin sloughing, so the patient was given topical mupirocin ointment to apply TID for 7 days. Her skin cleared after 3 weeks and all previous AKs were clinically eliminated.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

This was a vigorous response to the 5-FU treatment and was actually within the range of expected outcomes for a patient with a heavy burden of AKs. The erythema and superficial skin flaking spared areas unaffected by pre-cancers.

AKs manifest as rough, pink to brown macules or papules on sun-damaged skin and represent a precancerous change in keratinocytes that can lead to invasive squamous cell carcinoma. For this reason, AKs are often treated when they are observed. When targeting an entire “field” of AKs, a gold standard therapy is topical 5-FU. Prescribing 5-FU is safe and effective, but requires patient education, therapy customization, and anticipatory guidance.

Compared with other field treatments (eg, photodynamic therapy, topical diclofenac, imiquimod), 5-FU is the most successful and cost effective; it is first-line therapy and has the longest track record.1,2 5-FU represses DNA synthesis. It’s helpful to describe 5-FU to patients as “fake DNA” that targets precancerous cells that are dividing rapidly. But a word of caution: Patients should be advised, in advance, to avoid significant sun exposure while using 5-FU, as the drug will lose its targeted effect and cause more generalized skin damage.

Physicians can modulate the severity of the response to 5-FU by decreasing the frequency or length of therapy by using a weaker (and more expensive) once daily 0.5% long-acting formulation. Additionally, to improve comfort, low-potency topical steroids such as hydrocortisone ointment 0.5% to 2.5% can be applied after completion of therapy to speed up the healing process. These adjustments improve tolerance of therapy, but the precise effect on efficacy is unknown.

Because of the degree of redness and erythema that developed in this patient, treatment was stopped a week early. There was also concern about possible bacterial involvement in the heavy skin sloughing, so the patient was given topical mupirocin ointment to apply TID for 7 days. Her skin cleared after 3 weeks and all previous AKs were clinically eliminated.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Gupta AK, Paquet M. Network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169:250-259. doi: 10.1111/bjd.12343

2. Jansen MHE, Kessels JPHM, Merks I, et al. A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands. Br J Dermatol. 2020;183:738-744. doi: 10.1111/bjd.18884

References

1. Gupta AK, Paquet M. Network meta-analysis of the outcome 'participant complete clearance' in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol. 2013;169:250-259. doi: 10.1111/bjd.12343

2. Jansen MHE, Kessels JPHM, Merks I, et al. A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands. Br J Dermatol. 2020;183:738-744. doi: 10.1111/bjd.18884

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