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Microbiome: Gut dysbiosis linked to development of alopecia areata
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
presented at the annual meeting of the Society for Investigative Dermatology.
There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.
Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”
She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.
Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.
“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.
The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.
In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”
Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”
When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.
Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.
FMT not a ‘simple fix’ for AA
Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”
However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.
Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”
As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”
Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.
“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”
Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.
Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.
FROM SID 2021
Indoor tanning ICD-10 codes may be underused, study finds
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
according to a study presented at the annual meeting of the Society for Investigative Dermatology.
“Since indoor tanning ICD-10 codes were only recently universally implemented in 2015, and providers may still be using other codes that cover similar services, we think our data likely underestimate the number of encounters and sequelae associated with indoor tanning,” Alexandria M. Brown, BSA, of Baylor College of Medicine, Houston, said in her presentation. “We think increased usage of these indoor tanning exposure codes in coming years will strengthen this body of indoor tanning literature and data.”
Using insurance claims data on about 43 million patients from Truven Health MarketScan, Ms. Brown and colleagues analyzed patient encounters with ICD-10 indoor tanning codes W89.1, W89.1XXA, W89.1XXD, and W89.1XXS between 2016 and 2018 for about 43 million patients. Overall, there were 4,550 patient encounters where these codes had been recorded, with most (99%) occurring in an outpatient setting. The majority of providers at these encounters were dermatologists (72%). Patients were mostly women (85%); and most were ages 25-34 years (19.4%), 35-44 years (20.6%), 45-54 years (22.7%), and 55-64 years (19%). Almost 5% were 65 and over, 11.7% were ages 18-24, and 1.6% were under age 18.
The use of indoor tanning codes were most common in the Midwest (55 per 100,000 encounters with dermatologists), compared with 16 per 100,000 in the Northeast, 21 per 100,000 in the West, and 28 per 100,000 in the South. CPT codes for “destruction of a premalignant lesion” and “biopsy” were the most frequently used codes entered at visits where indoor tanning codes were also entered, and were present in 15.1% of encounters and 18.4% of encounters, respectively.
“This suggests that many of these encounters may have been for skin cancer surveillance and that indoor tanning exposure may have been coded as part of a patient’s skin cancer risk profile,” Ms. Brown noted.
The study shows how these codes are being used and could help determine health care use patterns for these patients as well as their comorbidities, behaviors, and risk factors, according to the authors, who believe this is the first study to look at the use of ICD-10 indoor tanning codes.
“Any effort to reduce indoor tanning requires knowledge of the population at risk. It has been shown that the ability to recognize and provide counseling to at-risk patients can improve sun protective behaviors and reduce indoor tanning,” Ms. Brown said. Claims databases can be a “valuable tool to better understand patients who have been exposed to indoor tanning and their associated risk factors, comorbidities, behaviors, and health care utilization.”
In an interview, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said the study was interesting and “provides some guidance with respect to who, when, and where in the U.S. to target educational initiatives on the harms of tanning beds.”
Dr. Friedman, who was not involved with the research, agreed with the authors’ assertion that their study was underestimating the use of indoor tanning beds. “Using a large database provides the means to better generalize one’s dataset; however in this case, it relies on proper coding by the practitioner,” or even using the code for tanning bed use at all.
“There also could be some inherent bias given most of the cases for which the code was used was for skin cancer surveillance, and therefore tanning bed use was top of mind,” he said.
While he believes this study may not be most efficient way of determining demographics of at-risk individuals using tanning beds, Dr. Friedman said the results “should serve as the impetus to develop public health campaigns around this information, following which research can be conducted to evaluate if the intervention had an impact.”
Ms. Brown and Dr. Friedman reported no relevant financial disclosures.
FROM SID 2021
Rate of cutaneous toxicities from ICIs may be lower than previously reported
A
, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
A
, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
A
, according to research presented at the annual meeting of the Society for Investigative Dermatology, held virtually.What’s more, many of the cutaneous immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) observed in the study may be unreported in clinical trial settings and by providers, according to one of the investigators, Yevgeniy Semenov, MD, MA, a dermatologist at Massachusetts General Hospital, Boston.
“Most cutaneous irAEs are low grade and might go unreported outside of clinical trial settings, as patients might not seek medical care, or when they do, providers might not report them in patient charts. As a result, the diagnoses identified in this study likely represent the most clinically relevant cutaneous events in the ICI population,” said Dr. Semenov, who presented the results at the meeting.
In the study, he said that one of the first issues he and his colleagues encountered was how to classify cutaneous irAEs, as they “can vary widely in morphology and severity.” Immune-related adverse events from ICIs are a “unique constellation of inflammatory toxicities,” affecting nearly every organ system, and may require treatment with immunosuppressive agents that can impact the effectiveness of the ICI. The matter is further complicated by a “lack of definitional standards of what constitutes a cutaneous immune-related adverse event, which greatly limits the research in this area,” Dr. Semenov said. There is also potential for misdiagnosis of irAEs as cutaneous eruptions occurring in patients receiving ICI therapy because of failure to account for the presence of skin disease at baseline, he pointed out.
Dr. Semenov noted that more than 40 cutaneous eruptions have been associated with ICI treatment. “Much of the observational data on cutaneous immune-related adverse events has been riddled with case reports and case series of cutaneous events that happen to be occurring in the setting of ICI therapy. These lack rigorous control groups and often associate events with little to no relationship to the actual ICI, which may have instead occurred in the setting of a competing medication,” he explained.
Real-world data
The researchers thus sought to identify the real-world incidence of cutaneous irAEs with population-level data. Using data from a national claims insurance database from January 2011 through 2019, they compared 8,637 of patients with cancer, treated with an ICI (who had not been treated with other cancer treatments within 6 months of starting an ICI) with 8,637 patients with cancer who were not treated with an ICI, matched for demographics, primary cancer type, and Charlson Comorbidity Index (CCI) score.
In both groups, the mean age of the patients was 67.5 years, 59.2% were men, and 93% had a severe CCI score. The most common cancer types were lung cancer (40%), melanoma (26.6%), and renal cell carcinoma (12.3%). The median follow-up time was 1.9 years, and the median treatment duration was 2.0 years.
Dr. Semenov and colleagues selected 42 dermatoses reported in the literature to evaluate and found an overall incidence of 25% within 2 years of starting ICI therapy. Of those 42 dermatoses, there were 10 with a significantly higher incidence among patients receiving ICIs, compared with controls: drug eruption or other nonspecific eruption (4.2%; incidence rate ratio, 5.00), bullous pemphigoid (0.3%; IRR, 4.91), maculopapular eruption (0.9%; IRR, 4.75), vitiligo (0.7%; IRR, 3.79), Grover’s disease (0.2%; IRR, 3.43), rash and other nonspecific eruption (9.0%; IRR, 2.34), mucositis (1.5%; IRR, 2.33), pruritus (4.8%; IRR, 1.92), lichen planus (0.5%; IRR, 1.75), and erythroderma (1.1%; IRR, 1.70).
After adjusting for a baseline history of squamous cell carcinoma and actinic keratosis, the researchers found that both were significantly less likely in patients receiving ICIs.
A delay in presentation of any cutaneous irAE after starting ICI therapy was also observed (a median of 16.1 weeks), which Dr. Semenov noted was longer than the 5 weeks reported in clinical trials. This delay in presentation increased to a median of 37.5 weeks for the 10 dermatoses with a significantly higher incidence among patients receiving ICIs, with 17.6% of patients presenting in the first month, 63.1% presenting by 6 months, and 84.6% presenting by 1 year.
Use of immunosuppressive treatment
The researchers also examined use of systemic immunosuppression for treating cutaneous toxicities, defined as “a new prescription for systemic glucocorticoids greater than 10 mg per day, prednisone equivalent, or nonsteroidal systemic immunosuppression,” administered within 7 days of the diagnosis of the cutaneous event. They found that 5% of patients overall received systemic immunosuppressive treatment within 7 days of a cutaneous event, which was “at the higher end of what was reported in clinical trials for the treatment of cutaneous toxicities,” Dr. Semenov noted.
“This is likely the result of the delays in diagnosis in nonclinical trial settings ... allowing more time for these events to progress to a higher grade. Also, there may be a greater willingness by providers to initiate systemic immunosuppression due to less stringent treatment protocols in real-world clinical settings,” he said.
Using a multivariable risk prediction model for cutaneous toxicities, the researchers identified use of ipilimumab, a CTLA-4-blocking antibody, as having a protective effect for not developing a cutaneous irAE, compared with the PD-1 blocker pembrolizumab (odds ratio, 0.78; 95% confidence interval, 0.62-0.98; P < .01). But combination ICI therapy (OR, 1.53; 95% CI, 1.25-1.88; P < .001), a melanoma diagnosis (OR, 2.47; 95% CI, 2.11-2.89; P < .001), and a renal cell carcinoma diagnosis (OR, 1.65; 95% CI, 1.36-2.00; P < .001) were found to be risk factors for developing cutaneous irAEs.
“The protective effect of ipilimumab identified in the study is interesting, as historically ipilimumab has been more likely to cause cutaneous toxicities,” Dr. Semenov said. “However, we believe that the majority of this association is mediated by the melanoma, for which ipilimumab was primarily used since its introduction. Independent of this relationship, it seems to be less likely to cause cutaneous toxicity than PD-1 inhibition, according to this data.”
Based on their findings, he said, “dermatologists can utilize this information to facilitate evaluations of high-risk patients so they can take steps to prevent progression to more severe toxicities and reduce reliance or systemic immunosuppression.”
The 25% real-world incidence of cutaneous irAEs observed in the study, Dr. Semenov said, is “somewhat lower than previous clinical trial estimates of over one-third of patients presenting with cutaneous toxicities” but he added that previous estimates were based primarily on studies of patients with melanoma.
That some patients delayed presentation with these conditions “should revise clinicians’ understanding of when to expect patients to present with these toxicities, and not to rule out a delayed onset of symptoms as being unrelated to immunotherapy,” Dr. Semenov said.
Most cutaneous irAEs are ‘manageable’
In an interview, Naiara Braghiroli, MD, PhD, a dermatologist at Baptist Health’s Miami Cancer Institute, Plantation, Fla., who was not an investigator in the study, noted that over the last decade, ICIs have “revolutionized the treatment of metastatic melanoma” and, more recently, the treatment of nonmelanoma skin cancers, with regard to survival rates and side effects.
She said that the results of the study show that “most of the cutaneous side effects are manageable with very few exceptions, like the cutaneous bullous disorders and rarely, more serious reactions [such as] Stevens-Johnson syndrome.”
The majority of the side effects are treatable “and when well controlled, the patient can have a good quality of life” during treatment, she added.
For future research, Dr. Braghiroli noted, it would be interesting to know more about whether the development of any specific cutaneous reaction associated with ICIs “is associated with a higher chance of good antitumor response,” as seen with other anticancer therapies such as epidermal growth factor receptor inhibitors.
Dr. Semenov and Dr. Braghiroli report having no relevant financial disclosures.
FROM SID 2021
Topical histone deacetylase inhibitor reduced BCC size in phase 2 study
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”
Remetinostat promising as topical BCC therapy
In an interview, Beth G. Goldstein, MD, a dermatologist and Mohs surgeon in Chapel Hill, N.C., noted that the preliminary study was “an exciting report of a safe, well-tolerated nonsurgical option for patients with superficial BCCs on the trunk and extremities,” which has potential to be used in the future for nonsuperficial BCCs. The study shows that superficial BCCs can respond at a rate of 100% on nonfacial areas, said Dr. Goldstein, who was not involved in the research. “These lesions can be quite large with higher chances of recurrence and difficulty with wound care.
“This type of directed therapy hopefully continues to be perfected for treatment of BCC that avoids scarring and is well tolerated,” she added.
Dr. Goldstein commented that complete pathological resolution of 54.8% “was still unacceptably low for the remaining tumor types.” For those cases, she said remetinostat could possibly “provide a topical option as an adjunctive treatment for potentially reducing the size of the BCC prior to surgical removal,” as an alternative to a systemic therapy like vismodegib (Erivedge).
Dr. Goldstein said the strengths of the study were in the variety of tumors, close follow-up with histologic evaluation and safety signals. In terms of limitations, she said whether there were any cases of Gorlin syndrome was not clear. In addition, at least 30% of BCCs have a mixed tumor type on Mohs surgery that differs from the original biopsy, and “there was no mention if the residual tumor remained with the same histology,” she said.
In the future, a large, randomized trial is warranted to stratify for Gorlin syndrome, patients who are immunosuppressed, and additional tumor types that were underrepresented in this study, such as micronodular tumors, Dr. Goldstein said. Future studies also should examine how remetinostat impacts BCC in facial areas, the effect of multiple applications, and how the therapy performs as an adjunctive treatment before surgery.
This study was funded by Medivir, the Damon Runyon Foundation, National Cancer Institute, an American Skin Association Hambrick Medical Student grant, and Stanford Medical Scholars. Dr. Kilgour and Dr. Goldstein reported no relevant financial disclosures.
FROM SID 2021
Cross-sectional study finds chronic skin conditions have highest opioid prescribing rates
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
at dermatology visits.
“Overall, opioid prescribing rates among dermatologists were low. However, dermatologists should remain aware of risk factors for long-term opioid use and consider using nonnarcotic or nonpharmacologic interventions when possible,” Sarah P. Pourali, a medical student at Vanderbilt University, Nashville, said at the annual meeting of the Society for Investigative Dermatology, where she presented the results.
Ms. Pourali said that although Mohs surgery and dermatologic procedures are the focus of “much of the literature” concerning opioid use in dermatology, there are limited data on medication prescribing patterns for other skin conditions treated by dermatologists.
She and her colleagues performed a cross-sectional study using data from the National Ambulatory Medical Care Survey (NAMCS) from 2009 to 2016 on 288,462,610 weighted dermatology visits. The researchers used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify dermatologic diseases. They also identified and grouped oral pain medication into the following categories: opiate analgesics, nonsteroidal anti-inflammatory drugs, acetaminophen, and gabapentin. A linear regression analysis was used to evaluate pain medicine prescribing each year, and the researchers used a logistic regression analysis to explore how opiate prescriptions were connected to patient clinical characteristics. The analysis was adjusted for age, gender, race, ethnicity, and region.
Overall, most dermatology visits were for patients older than 65 years (36.2%) and 45-64 years old (32.1%). Over half of the dermatologist visits were for women (56.4%) and most (92.2%) visits were for patients who were White (5.1 % were for patients who were Black); most were non-Hispanic or Latino (93.5%). Most dermatology visits were in the South (35.4%) and West (25.2%), followed by the Northeast (21.9%) and Midwest (17.5%).
Opioids were prescribed in 1.3% of the visits, Ms. Pourali said. In addition, 4.7% of visits included an NSAID prescription, 0.7% an acetaminophen prescription, and 0.6% a gabapentin prescription.
Dermatologic procedure visits accounted for 43.1% of opioid prescriptions, she noted. The most common skin conditions for which opioids were prescribed included vitiligo (10.3%), hemangioma (3.8%), pemphigus (3.6%), atopic dermatitis (3.4%), and psoriasis (2.5%).
Although patients older than 65 years accounted for 36.2% of visits to dermatologists, 58.5% of opioids prescribed by dermatologists were for patients in this age group. “We hypothesize that this may be due to a higher proportion of older patients requiring skin cancer surgeries where a lot of opioids are prescribed within dermatology,” Ms. Pourali said.
The highest population-adjusted prescription rates for opiates were in the Northeast and Western regions of the United States, which “partially corroborates” previous studies that have found “higher rates of opioid prescribing in the southern and western U.S.,” she noted.
When evaluating risk-factors for long-term opiate use, Ms. Pourali and colleagues found opioids were also prescribed in 13.2% of visits where a benzodiazepine was prescribed (adjusted odds ratio, 8.17; 95% confidence interval, 5.3-12.7), 8.4% of visits where the patient had a substance abuse disorder (adjusted OR, 9.40; 95% CI, 2.0-44.4), 5.2% of visits with a patient who had depression (adjusted OR, 3.28; 95% CI, 2.0-5.4), and 2.4% of visits with a patient who used tobacco (adjusted OR, 1.09; 95% CI, 1.0-1.1).
Consider nonopioid postoperative pain management options
In an interview, Sailesh Konda, MD, associate clinical professor of dermatology and director of Mohs surgery and surgical dermatology at the University of Florida, Gainesville, who was not involved with the research, noted the finding in the study that vitiligo, hemangioma, pemphigus, AD, and psoriasis were diagnoses with the highest rates of opioid prescription was surprising. “In general, these are conditions that are not routinely managed with opioids,” he said.
NAMCS contains a primary diagnosis field and space for four additional diagnoses such as chronic conditions, as well as thirty fields for medications. “If an opioid was prescribed at a visit, it could have been prescribed for any of the diagnoses related to the visit,” Dr. Konda said. “Additionally, for those opioid prescriptions associated with dermatologic procedures, it would have been helpful to have a breakdown of the specific procedures.”
Dr. Konda compared these results to a recent study of opioid prescribing patterns in the dermatology Medicare population, which found that 93.9% of the top 1% of opioid prescribers were dermatologists working in a surgical practice.
He said that recommendations for opioid prescribing should be developed for general dermatology as they have been for Mohs surgery and dermatologic surgery. For dermatologists currently prescribing opioids, he recommended monitoring prescribing patterns and to “consider nonopioid interventions, such as acetaminophen plus ibuprofen, which has been found to effectively control postoperative pain with fewer complications.”
Ms. Pourali reports no relevant financial disclosures. Her coauthors included the principal investigator, April Armstrong, MD, MPH, professor of dermatology, University of Southern California, Los Angeles. Dr. Konda reports no relevant financial disclosures.
FROM SID 2021