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Skin reactions to first COVID-19 vaccine don’t justify forgoing second dose
BOSTON – Requests for a according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.
According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.
This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.
Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.
“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”
This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.
After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.
“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.
These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.
“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.
“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.
Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.
Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.
Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.
Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.
Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.
The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.
“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.
After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.
Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.
“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”
Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”
Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.
Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – Requests for a according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.
According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.
This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.
Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.
“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”
This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.
After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.
“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.
These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.
“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.
“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.
Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.
Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.
Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.
Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.
Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.
The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.
“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.
After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.
Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.
“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”
Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”
Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.
Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – Requests for a according to an analysis of several large sets of data presented at the annual meeting of the American Academy of Dermatology.
According to the data, “there are no serious adverse consequences from these cutaneous reactions,” said Esther Freeman, MD, PhD, director of Global Health Dermatology, Massachusetts General Hospital, Boston.
This is important because the risk of vaccine hesitancy goes up dramatically in patients who experience reactions to the first vaccine dose, according to follow-up of more than 50,000 employees vaccinated in the Mass General Brigham Healthcare System (MGBHS). According to Dr. Freeman, there was almost a fourfold increase in the rate of second-dose refusals for those with cutaneous reactions and a more than fourfold increase in those who developed angioedema.
Before the data were available, skin reactions were a source of concern among dermatologists and others involved in monitoring vaccine-related adverse events. Injection site reactions (ISRs) are associated with essentially every injectable vaccine, so these were expected, but a small proportion of patients developed large red plaques in the injection arm 7-8 days after the inoculation.
“These delayed reactions caused a lot of initial panic,” said Dr. Freeman, who counted herself among those alarmed about what the reactions might signify. “Was this cellulitis? Would the next dose cause anaphylaxis? We were concerned.”
This concern dissipated with the availability of more data. In a global registry that has so far captured more than 1,000 cutaneous reactions from 52 participating countries, it appears that about 2% of patients have a cutaneous reaction other than an ISR after the first dose. All resolve with minimal skin care or no treatment.
After the second dose, the proportion is lower. If there is a reaction, it typically occurs earlier and resolves more quickly.
“What we have learned is that fewer than half of patients who had a reaction to the first dose have a reaction to the second, and those who did have a reaction had a milder course,” said Dr. Freeman.
These data are “incredibly reassuring” on many levels, she explained. In addition, it allows clinicians to confidently explain to patients that there are no serious sequelae from the rashes, whether immediate or delayed, from the available COVID-19 vaccines.
“Every skin reaction I have seen is something we can treat through,” she added, noting that most reactions resolve with little or no supportive care. Following skin reactions, particularly the delayed lesions, it is not uncommon for patients to refuse a second shot. Some request a medical waiver to avoid further vaccine exposure. According to Dr. Freeman, this is unwarranted.
“I have granted exactly zero waivers,” she said. She explains to patients that these reactions have not been predictive of serious events, such as anaphylaxis. Although the trigger of the hypersensitivity reaction remains unknown, there is no evidence of serious consequences.
Delayed skin reactions are more commonly associated with the Moderna than the Pfizer vaccine. One notable difference between these vaccines is the greater content of mRNA in the Moderna formulation, but Freeman said that this is only one potential hypothesis for higher frequency of reactions to this version of the vaccine.
Patients with a history of allergic disease are more likely to develop a reaction but not significantly more likely to have a reaction that is more difficult to manage, according to Kimberly G. Blumenthal, MD, quality and safety officer for allergy, and codirector of the clinical epidemiology program in the division of rheumatology, allergy, and immunology at Mass General.
Anaphylaxis has been associated with COVD-19 vaccines just as it has with essentially every injectable vaccine, Dr. Blumenthal said during the same session. But the risk is very low, and it stays low even among those with a history of severe hypersensitivity reactions in the past.
Among the data collected from more than 52,000 vaccinated MGBHS employees, 0.9% had a history of severe allergic reaction to a prior vaccine. Of these, 11.6% had an allergic reaction to the COVID-19 vaccine. This was more than twice the 4.6% rate of allergic reactions among employees without a history of allergic reactions, but serious consequences were rare in both groups.
Of those with a reaction to the first dose, all but 2.4% took a subsequent dose. Again, serious reactions were exceedingly rare. These serious reactions did include anaphylaxis and hospitalization in 3% of patients, but there were no fatalities and all resolved.
The absence of serious sequelae from a reaction to a COVID-19 vaccine must be considered within the context of the benefit, which includes protection from death and hospitalization from the virus, according to Dr. Blumenthal. Citing the evidence that first-shot reactions are a source of vaccine hesitancy, she agreed that it is important to educate patients about relative risks.
“Even in our own cohort of MGBHS employees, we have people, including those who had been provaccine in the past, become hesitant,” commented Dr. Blumenthal, who said there are data from the Kaiser Permanente System showing similar vaccine reluctance following a first-shot reaction.
After more than 500 million doses of the Moderna and Pfizer vaccines had been administered worldwide, there was not a single reported death from anaphylaxis. Although Dr. Blumenthal said that an unconfirmed death of this type had been recently reported, she emphasized that this single death, if valid, is dwarfed by the lives saved with vaccination.
Asked about her strategy for counseling patients with vaccine hesitancy, Dr. Freeman said the body of safety data is large and compelling. There is overwhelming evidence of a favorable benefit-to-risk ratio overall and among those with a first-shot reaction.
“I can reassure them on the basis of the data,” Dr. Freeman said in an interview. “Less than half will have a reaction to the second shot and even if they do have a reaction, it is likely to be less severe.”
Although the main message is that vaccination is potentially lifesaving and far outweighs any risks, Freeman specifically gives this message to those hesitant to take a second shot after a first-shot reaction: “I can get you through it.”
Dr. Freeman encouraged health care professionals to report cases of COVID-19 vaccine–related dermatologic side effects to the American Academy of Dermatology / International League of Dermatologic Societies COVID-19 dermatology registry. Dermatologic manifestations of COVID-19 can also be reported to the registry.
Dr. Freeman disclosed receiving grants/research funding from the International League of Dermatologic Societies and from the National Institutes of Health. Dr. Blumenthal disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Cellulitis care costly from misdiagnosis, needless hospitalizations
BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.
“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.
“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.
Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.
Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.
Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.
Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.
“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.
Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.
Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.
“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.
For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.
“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.
For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.
Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.
When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.
True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”
Following publication of his study, he became involved in addressing this issue at his institution.
“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.
Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.
Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.
“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.
“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.
Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.
Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.
Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.
Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.
“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.
Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.
Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.
“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.
For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.
“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.
For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.
Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.
When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.
True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”
Following publication of his study, he became involved in addressing this issue at his institution.
“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.
Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.
Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The cost of care for the more than 14 million cases of cellulitis that occur each year in the United States is in the billions of dollars, but there are multiple opportunities, many involving dermatologists, to dramatically reduce these costs, according to an outline of strategies presented at the American Academy of Dermatology 2022 annual meeting in Boston.
“Cellulitis is misdiagnosed about one-third of the time, and that cost is very high,” reported Jennifer L. Adams, MD, assistant professor of dermatology, University of Nebraska, Omaha. She sees opportunities for dermatological consults to help weed through the many cellulitis mimickers, such as venous insufficiency or psoriasiform drug reactions, to prevent unnecessary admissions and ineffective therapy.
“There is a huge need for diagnostic accuracy as a means to deliver more cost-effective care,” Dr. Adams said.
Solving misdiagnosis is only part of the story. Costs of care are also ramped up by unnecessary hospitalizations. According to Dr. Adams, published criteria to triage emergency room patients with cellulitis to outpatient care are not always followed. In one review, 14% of admitted patients had met the criteria for outpatient treatment.
Cellulitis is a common skin infection that causes redness, swelling, and pain in the infected area, most often on the legs and feet.
Unnecessary hospitalizations for misdiagnosed cellulitis, which is associated with an average 4-day hospital stay, “range from $200 million to $500 million in avoidable direct healthcare costs,” Dr. Adams said.
Even for justifiable hospitalizations, there are still opportunities for cost savings. In one study, blood cultures were ordered in 73% of patients even though only 2% produced a finding relevant to care. According to Dr. Adams, most cellulitis cases are caused by the “usual suspects” – group A beta-hemolytic streptococcus, Streptococcus pneumoniae, and Staphylococcus aureus. The exceptions stand out by clinical criteria, such as known neutropenia, history of an animal bite, signs of Systemic Inflammatory Response Syndrome (SIRS), or a purulent appearance.
“Blood cultures are not cost-effective in uncomplicated cellulitis,” Dr. Adams said. She said there are numerous published algorithms to guide clinicians on decision-making in the management of soft tissue infections, including cellulitis, including a much-cited algorithm first published more than 15 years ago and updated in 2014.
Similarly, labs and imaging are commonly ordered with no strong likelihood that they will change management, she said. These types of decisions are also covered in published algorithms.
Strategies to prevent rehospitalization are another area where there is a large opportunity to reduce health care resources consumed by cellulitis. The rehospitalization rate at 30 days is approximately 10%, but many patients have recurrent episodes over years, according to Dr. Adams. The risk factors and the preventative measures have been well described.
“Scrupulous clinical care can reduce recurrence, and it is cost-effective,” said Dr. Adams, referring to control of edema, control of underlying conditions associated with increased risk, such as diabetes, and managing dry skin and erosions with topical agents or even moisturizers. Compression socks are a simple but effective tool, she added.
For patients with repeat episodes of cellulitis over years, Dr. Adams referred to a double-blind trial that associated a twice-daily dose of 250 mg penicillin with a 45% reduction in the risk of cellulitis recurrence over 1 year. At approximately $10 a month for this treatment, she said it is very cost-effective, although she acknowledged that recurrence rates of cellulitis climb back up when the penicillin is stopped.
“I think of this as a bridge while you work on addressing the venous insufficiency or other risk factors for cellulitis,” Dr. Adams said.
For reducing the costs of cellulitis, there is evidence that dermatologists can play a role. Dr. Adams cited a study that evaluated the impact of a dermatologist consultation for suspected cellulitis in the emergency room or within 24 hours of admission. Of 34 patients already prescribed antibiotics for presumed cellulitis, discontinuation was recommended in 82%. Of 39 admissions, pseudocellulitis was identified in 51%.
Extrapolating these data to national rates of cellulitis, there was an estimated savings of up to $200 million annually without any apparent increased risk of adverse outcomes, according to Dr. Adams.
When contacted about his experience, the senior investigator of that study, Arash Mostaghimi, MD, director of the Inpatient Dermatology Consult Service, Brigham and Women’s Hospital, Boston, largely agreed with the premise of Adam’s analysis. In particular, he said, avoiding misdiagnosis of cellulitis offers a major opportunity to lower costs while possibly improving care.
True of national practice and at the local level, “misdiagnosis of noninfectious inflammatory reactions such as cellulitis has substantial cost impacts,” Dr. Mostaghimi said in an interview. Based on evidence, the savings are derived directly from “unnecessary antibiotic exposure as well as inappropriate hospitalization.”
Following publication of his study, he became involved in addressing this issue at his institution.
“At Brigham and Women’s, we collaborated with colleagues in infectious disease and in the emergency department to create cellulitis protocols that identify patients at risk for misdiagnosis and facilitate early dermatology consultation for diagnostic confirmation,” he said.
Although there are algorithms to achieve this goal, he indicated that the expertise of dermatologists can quickly and efficiently differentiate inflammatory skin reactions and expedite appropriate care.
Dr. Adams and Dr. Mostaghimi have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Global registry tracks COVID-19 outcomes in atopic dermatitis patients
BOSTON – , results from a global registry demonstrated.
Moreover, combination systemic treatment, especially those that included systemic corticosteroids, was associated with the highest risk of COVID-19–related hospitalization.
“Patients with inflammatory skin diseases such as AD may be at higher risk of COVID-19,” Annelie H. Musters, MD, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “Another factor to consider is that AD patients are often treated with systemic immunomodulatory therapy, including systemic corticosteroids and nonsteroidal immunosuppressants such as methotrexate, cyclosporin, biologics, and Janus kinase inhibitors. Different mechanisms of action and levels of immunosuppression may impart variable risks of serious infections.”
On the other hand, some degree of immunomodulation may have beneficial effects on the course of COVID-19 in AD patients, said Dr. Musters, of the department of dermatology at Academic Medical Center, University of Amsterdam. Targeting of specific immune pathways could reduce the development of a hyperinflammatory state in severe COVID-19. Dual blockade of interleukin (IL)-4 and IL-13 with dupilumab may have a protective effect in the context of COVID-19 infection, because expression of Th2 cytokines, including IL-4 and IL-13, may be increased during COVID-19.
“At the start of the pandemic, many of us were faced with important questions, like do systemic immunomodulatory treatments influence outcomes of COVID-19 in patients with AD?” she said. “Do patients on dupilumab or other novel systemics fare better than those on conventional systemic treatment?”
To answer these questions, she and her colleagues launched a web-based registry in April 2020 to investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments. For the registry, known as Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD), clinicians in 27 countries used a web-based form to enter anonymized data after patients had fully recovered from COVID-19. Eligibility criteria included having proven or highly suspected COVID-19, and there were no restrictions on age nor the type of AD treatment they were receiving.
Dr. Musters reported results from 442 patients who were recruited between April 2, 2020, and Oct. 31, 2021. Their mean age was 35.6 years, their median body mass index was 23.7 kg/m2, and there was an even sex distribution. Most patients were White and were recruited from Italy. Of the 442 patients, 216 (48.8%) received dupilumab monotherapy, 131 (29.6%) received topical treatments, and 14 (3.16%) received combination systemic treatments, including systemic corticosteroids. About 12% presented to the emergency department and 6% were hospitalized. Of those hospitalized, 2% required intensive care and/or ventilation, and no deaths have occurred in the registry to date.
By treatment group, hospitalization rates were highest among those on combination treatments (35.7%), followed by systemic corticosteroids (14.3%), topical treatments only (9.9%), other conventional systemics (3.6%), methotrexate (3.3%), and dupilumab (2.3%).
To further explore the differences between hospitalization rates in treatment groups, the researchers performed a multivariable logistic regression analysis, adjusted for age, sex, ethnicity, and comorbidity score. Compared with those who received dupilumab, the adjusted odds ratios (ORs) for hospitalization were highest among those who received topical treatments (OR, 4.95), followed by those who received systemic corticosteroids (OR, 2.81), and those who received other conventional systemic treatments (OR, 2.36).
Dr. Musters and colleagues also found that compared with patients on nonsteroidal immunosuppressive therapy, patients on combination systemic therapy had a significantly higher odds of hospitalization, specifically an OR of 45.75 for those on combination treatment including corticosteroids, an OR of 37.57 for those on combination treatment not including steroids, and an OR of 1.87 for those on systemic corticosteroids as monotherapy.
“Overall, the risk of COVID-19 complications appears to be low in patients with AD, even when treated with systemic immunomodulatory agents,” Dr. Musters concluded. “Dupilumab monotherapy was associated with lower odds of hospitalizations compared with other therapies. Moreover, combination systemic treatment, especially combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.”
She added that other population-based study designs are more suitable to answer other important questions, such as whether the overall risk of COVID-19 in patients with AD is higher or lower compared to healthy controls.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, characterized the results as reassuring. In this patient population, “we expected that dupilumab would not cause any problems,” she said. “We wouldn’t necessarily expect it to [confer] a benefit, but I think it’s because the patients who need a systemic medication are going on something that’s very targeted (dupilumab) rather than something that has a broader immunosuppressing function. It was interesting but not surprising that those on systemic steroids had more of a problem. Get them on something that’s very targeted if you can and don’t suppress the immune systems that might be handling COVID-19.”
Dr. Musters reported having no disclosures. Dr. Paller disclosed that she is consultant to and/or an investigator for many pharmaceutical companies.
BOSTON – , results from a global registry demonstrated.
Moreover, combination systemic treatment, especially those that included systemic corticosteroids, was associated with the highest risk of COVID-19–related hospitalization.
“Patients with inflammatory skin diseases such as AD may be at higher risk of COVID-19,” Annelie H. Musters, MD, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “Another factor to consider is that AD patients are often treated with systemic immunomodulatory therapy, including systemic corticosteroids and nonsteroidal immunosuppressants such as methotrexate, cyclosporin, biologics, and Janus kinase inhibitors. Different mechanisms of action and levels of immunosuppression may impart variable risks of serious infections.”
On the other hand, some degree of immunomodulation may have beneficial effects on the course of COVID-19 in AD patients, said Dr. Musters, of the department of dermatology at Academic Medical Center, University of Amsterdam. Targeting of specific immune pathways could reduce the development of a hyperinflammatory state in severe COVID-19. Dual blockade of interleukin (IL)-4 and IL-13 with dupilumab may have a protective effect in the context of COVID-19 infection, because expression of Th2 cytokines, including IL-4 and IL-13, may be increased during COVID-19.
“At the start of the pandemic, many of us were faced with important questions, like do systemic immunomodulatory treatments influence outcomes of COVID-19 in patients with AD?” she said. “Do patients on dupilumab or other novel systemics fare better than those on conventional systemic treatment?”
To answer these questions, she and her colleagues launched a web-based registry in April 2020 to investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments. For the registry, known as Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD), clinicians in 27 countries used a web-based form to enter anonymized data after patients had fully recovered from COVID-19. Eligibility criteria included having proven or highly suspected COVID-19, and there were no restrictions on age nor the type of AD treatment they were receiving.
Dr. Musters reported results from 442 patients who were recruited between April 2, 2020, and Oct. 31, 2021. Their mean age was 35.6 years, their median body mass index was 23.7 kg/m2, and there was an even sex distribution. Most patients were White and were recruited from Italy. Of the 442 patients, 216 (48.8%) received dupilumab monotherapy, 131 (29.6%) received topical treatments, and 14 (3.16%) received combination systemic treatments, including systemic corticosteroids. About 12% presented to the emergency department and 6% were hospitalized. Of those hospitalized, 2% required intensive care and/or ventilation, and no deaths have occurred in the registry to date.
By treatment group, hospitalization rates were highest among those on combination treatments (35.7%), followed by systemic corticosteroids (14.3%), topical treatments only (9.9%), other conventional systemics (3.6%), methotrexate (3.3%), and dupilumab (2.3%).
To further explore the differences between hospitalization rates in treatment groups, the researchers performed a multivariable logistic regression analysis, adjusted for age, sex, ethnicity, and comorbidity score. Compared with those who received dupilumab, the adjusted odds ratios (ORs) for hospitalization were highest among those who received topical treatments (OR, 4.95), followed by those who received systemic corticosteroids (OR, 2.81), and those who received other conventional systemic treatments (OR, 2.36).
Dr. Musters and colleagues also found that compared with patients on nonsteroidal immunosuppressive therapy, patients on combination systemic therapy had a significantly higher odds of hospitalization, specifically an OR of 45.75 for those on combination treatment including corticosteroids, an OR of 37.57 for those on combination treatment not including steroids, and an OR of 1.87 for those on systemic corticosteroids as monotherapy.
“Overall, the risk of COVID-19 complications appears to be low in patients with AD, even when treated with systemic immunomodulatory agents,” Dr. Musters concluded. “Dupilumab monotherapy was associated with lower odds of hospitalizations compared with other therapies. Moreover, combination systemic treatment, especially combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.”
She added that other population-based study designs are more suitable to answer other important questions, such as whether the overall risk of COVID-19 in patients with AD is higher or lower compared to healthy controls.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, characterized the results as reassuring. In this patient population, “we expected that dupilumab would not cause any problems,” she said. “We wouldn’t necessarily expect it to [confer] a benefit, but I think it’s because the patients who need a systemic medication are going on something that’s very targeted (dupilumab) rather than something that has a broader immunosuppressing function. It was interesting but not surprising that those on systemic steroids had more of a problem. Get them on something that’s very targeted if you can and don’t suppress the immune systems that might be handling COVID-19.”
Dr. Musters reported having no disclosures. Dr. Paller disclosed that she is consultant to and/or an investigator for many pharmaceutical companies.
BOSTON – , results from a global registry demonstrated.
Moreover, combination systemic treatment, especially those that included systemic corticosteroids, was associated with the highest risk of COVID-19–related hospitalization.
“Patients with inflammatory skin diseases such as AD may be at higher risk of COVID-19,” Annelie H. Musters, MD, said during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “Another factor to consider is that AD patients are often treated with systemic immunomodulatory therapy, including systemic corticosteroids and nonsteroidal immunosuppressants such as methotrexate, cyclosporin, biologics, and Janus kinase inhibitors. Different mechanisms of action and levels of immunosuppression may impart variable risks of serious infections.”
On the other hand, some degree of immunomodulation may have beneficial effects on the course of COVID-19 in AD patients, said Dr. Musters, of the department of dermatology at Academic Medical Center, University of Amsterdam. Targeting of specific immune pathways could reduce the development of a hyperinflammatory state in severe COVID-19. Dual blockade of interleukin (IL)-4 and IL-13 with dupilumab may have a protective effect in the context of COVID-19 infection, because expression of Th2 cytokines, including IL-4 and IL-13, may be increased during COVID-19.
“At the start of the pandemic, many of us were faced with important questions, like do systemic immunomodulatory treatments influence outcomes of COVID-19 in patients with AD?” she said. “Do patients on dupilumab or other novel systemics fare better than those on conventional systemic treatment?”
To answer these questions, she and her colleagues launched a web-based registry in April 2020 to investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments. For the registry, known as Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD), clinicians in 27 countries used a web-based form to enter anonymized data after patients had fully recovered from COVID-19. Eligibility criteria included having proven or highly suspected COVID-19, and there were no restrictions on age nor the type of AD treatment they were receiving.
Dr. Musters reported results from 442 patients who were recruited between April 2, 2020, and Oct. 31, 2021. Their mean age was 35.6 years, their median body mass index was 23.7 kg/m2, and there was an even sex distribution. Most patients were White and were recruited from Italy. Of the 442 patients, 216 (48.8%) received dupilumab monotherapy, 131 (29.6%) received topical treatments, and 14 (3.16%) received combination systemic treatments, including systemic corticosteroids. About 12% presented to the emergency department and 6% were hospitalized. Of those hospitalized, 2% required intensive care and/or ventilation, and no deaths have occurred in the registry to date.
By treatment group, hospitalization rates were highest among those on combination treatments (35.7%), followed by systemic corticosteroids (14.3%), topical treatments only (9.9%), other conventional systemics (3.6%), methotrexate (3.3%), and dupilumab (2.3%).
To further explore the differences between hospitalization rates in treatment groups, the researchers performed a multivariable logistic regression analysis, adjusted for age, sex, ethnicity, and comorbidity score. Compared with those who received dupilumab, the adjusted odds ratios (ORs) for hospitalization were highest among those who received topical treatments (OR, 4.95), followed by those who received systemic corticosteroids (OR, 2.81), and those who received other conventional systemic treatments (OR, 2.36).
Dr. Musters and colleagues also found that compared with patients on nonsteroidal immunosuppressive therapy, patients on combination systemic therapy had a significantly higher odds of hospitalization, specifically an OR of 45.75 for those on combination treatment including corticosteroids, an OR of 37.57 for those on combination treatment not including steroids, and an OR of 1.87 for those on systemic corticosteroids as monotherapy.
“Overall, the risk of COVID-19 complications appears to be low in patients with AD, even when treated with systemic immunomodulatory agents,” Dr. Musters concluded. “Dupilumab monotherapy was associated with lower odds of hospitalizations compared with other therapies. Moreover, combination systemic treatment, especially combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.”
She added that other population-based study designs are more suitable to answer other important questions, such as whether the overall risk of COVID-19 in patients with AD is higher or lower compared to healthy controls.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, characterized the results as reassuring. In this patient population, “we expected that dupilumab would not cause any problems,” she said. “We wouldn’t necessarily expect it to [confer] a benefit, but I think it’s because the patients who need a systemic medication are going on something that’s very targeted (dupilumab) rather than something that has a broader immunosuppressing function. It was interesting but not surprising that those on systemic steroids had more of a problem. Get them on something that’s very targeted if you can and don’t suppress the immune systems that might be handling COVID-19.”
Dr. Musters reported having no disclosures. Dr. Paller disclosed that she is consultant to and/or an investigator for many pharmaceutical companies.
AT AAD 22
Clinical clarity grows about toenail disorder, experts report
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
BOSTON – The main commonly leading to the wrong therapy and no resolution to the problem, according to an expert update at the annual meeting of the American Academy of Dermatology.
Misinterpretation of the yellow discoloration, a common feature of retronychia, means “many patients are maintained on antifungal therapy for years and years with no change in their condition,” reported Phoebe Rich, MD, director of the Nail Disorders Clinic, Oregon Health & Science University, Portland.
Infection is not commonly involved in retronychia, but importantly, antifungals and antibiotics “have no role in treating the underlying disorder,” Dr. Rich said.
The term retronychia and its description is only about 20 years old, according to Dr. Rich, who cited work by David A. de Berker, MBBS, PhD, a consultant dermatologist at University Hospitals in Bristol, England. His publication on this disorder appeared in 1999, with a more detailed description published about 10 years later.
Recently, the body of literature on this disorder has been growing, contributing to an increasing consensus about etiology, diagnosis, and treatments to consider in the context of causes and severity, Dr. Rich said.
Some but not all patients have abnormal formation of the nail bed, increasing susceptibility to retronychia, but trauma or microtrauma typically serve as a trigger in most cases. Dancing, high heels, steel-toed shoes, and other sources of trauma to the toes are implicated.
Whether or not patients have an inherent susceptibility, injury separates the existing nail from the matrix and nail bed so that newly forming nail begins to grow under the nail rather continuing to push out the old nail.
Susceptibility is increased substantially in individuals with a shortened nail bed, according to Dr. Rich. In severe cases, when there is simply inadequate nail bed for the nail growth to attach, recurrence is common or even inevitable. Even when the nail is removed and regrowth appears normal at the end of a year, those patients with very short nail beds cannot count on a cure.
“Due to the slow growth of nails, it might take 2 or 3 years for the problem to recur,” Dr. Rich cautioned. For this reason, cure rates reported for the various interventions at 1 year might not predict longer-term benefit.
Retronychia is usually a clinical diagnosis based on the presence of the increased bulk of the toenail when overlapping nails cannot be seen. This is not necessarily a single overgrowth. In some cases, multiple layers of nails are stacked one on top of the other. Xanthonychia (yellow nail) is usually present.
“The layering might not be visible without removing the nail,” said Dr. Rich, explaining one reason that the diagnosis is sometimes missed. Ultrasound is a noninvasive means to confirm the problem, although Rich warned that imaging is not necessarily reimbursed.
“There is no diagnosis by histopathology, so it cannot be confirmed with biopsy,” Dr. Rich said.
Treatments range from conservative strategies, particularly topical or intralesional steroids in mild cases, to more invasive procedures such as clipping of the nail plate or surgical avulsion. All can be effective when used appropriately, according to Dr. Rich.
“The more invasive procedures are the more effective, but the caveat is they are also associated with more complications,” said Dr. Rich, citing, for example, the risk of nail dystrophies. Because of the increasing number of studies, the relative benefits and risks of retronychia treatment have now been summarized in a recent review. Dr. Rich suggested the review is one of the most recent and detailed evaluations of the topic that “I encourage everyone to read.”
Despite progress in describing retronychia, Dr. Rich said that there might be more to learn about risk. In particular, she cited the work of Dana W. Stern, MD, a specialist in nail disorders who is in private practice in New York. Dr. Stern is pursuing a hypothesis that at least some cases are caused by potentially targetable biomechanical issues.
“I have observed that many of the younger patients in my practice with retronychia seem to have atypical foot anatomy,” Dr. Stern said in an interview. “I am collecting cases and hoping to explore this issue in more depth.”
She said that foot anatomy in relationship to retronychia has not been adequately evaluated.
“In my review of the literature, I could not find a single study that showed imagery of the feet,” she said. She is considering a collaboration with others, including Rich, to explore this as a factor in retronychia.
Asked about risk of misdiagnosis, Dr. Stern reiterated some of the points made by Dr. Rich. In particular, she agreed that discolored nails alone should not be a reason to initiate antimycotic therapy without considering the possibility of retronychia.
“So many providers are not familiar with the diagnosis, and only 50% of yellow thickened nails are in fact onychomycosis,” she said. “We end up seeing a plethora of patients [with retronychia] who are unfortunately misdiagnosed for years.”
Dr. Rich reported financial relationships with numerous pharmaceutical companies. Dr. Stern reported a financial relationship with Rare Beauty Brands. Neither Dr. Rich nor Dr. Stern said they had any disclosures related to this topic.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Sustained jawline definition from hyaluronic gel, study reports
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
BOSTON – After several promising early phase studies, from what study authors characterized as a “pivotal” randomized multicenter trial. The results were presented during a late-breaking research session at the annual meeting of the American Academy of Dermatology.
The primary outcome, assessed at 6 months, was at least a 1-point improvement in a photonumeric scale used to grade jawline sagging, reported Jeremy Green, MD, Skin Associates of South Florida, Coral Gables.
When those randomized to the hyaluronic filler gel VYC-25L (Vycross, Juvéderm) were compared with untreated controls, 68.5% versus 38.4% met the criterion for benefit at 6 months. Importantly, the effect in treated patients was sustained when reevaluated at 12 months. Green reported that the response is generally sustained at the maximum follow-up, now out to 17 months.
Most enrolled patients are severely affected
In this study, 208 patients with severe (74%) or moderate loss of jawline definition were randomized in a 3:1 ratio to receive the filler or serve as controls. The initially untreated controls received the gel after the primary outcome analysis at 6 months.
The hyaluronic gel was injected at five sites along the jawline. The mean age of participants was 58 years. The majority were women, and most were White.
Dermatologists blinded to treatment compared photos at 6 months with those taken at baseline using the photonumeric grading system of 1-5. Change in patient satisfaction at 6 months and again at 12 months relative to baseline was also evaluated.
From baseline, when 28.9% of participants reported satisfaction on the Global Aesthetic Improvement Scale (GAIS), rates rose to 89.0% at month 6. There was a decline at month 12, but 79.9% remained satisfied after this period of follow-up.
Most patients experienced injection site reactions that were mainly mild to moderate and all resolved within several days of treatment. Pain with mastication was initially reported by 1.9%, but again this complaint was also mild and transient. All complaints had largely resolved by day 3.
The results are consistent with several previous clinical studies of VYC-25L for the same indication. In a similarly designed trial conducted in Europe that also used a 3:1 randomization scheme, the primary outcome assessed at 3 months was change in facial angle. Relative to controls, the angle improved by 2.51 degrees (P < .0001).
Patient satisfaction supports filler benefit
In the similar European trial, the clinical significance of the objective primary outcome also was supported by patient satisfaction assessed with several instruments, including the GAIS. Some degree of swelling or tenderness was experienced by almost all patients after injection, but none were serious, and all resolved.
In another trial, 202 patients with chin retrusion were randomized in a 3:1 ratio to VYC-25L or a control group. In that study, the primary outcome was at least a 1-point improvement in the Allergan Chin Retrusion Scale at 6 months. This advantage for treatment (56.3% vs. 27.5%) was again supported by several instruments for evaluating patient satisfaction, including GAIS.
As in the other studies, most patients had injection site reactions. Although all resolved within days of treatment, one patient left the study after experiencing cellulitis and injection-site inflammation.
Dissatisfaction with jawline definition is a relatively common complaint in Dr. Green’s experience, who said that there is a need for more effective and well-tolerated treatments. Given the efficacy, tolerability, and safety of VYC-25L in this controlled study, he suggested this product has potential utility.
In the field of cosmetic dermatology, there appears to be incremental progress in fillers with favorable clinical characteristics, according to Sandy U. Tsao, MD, a dermatologic surgeon at Massachusetts General Hospital, Boston.
“We are seeing filler lasting longer and longer,” she said, commenting specifically about the results presented by Dr. Green. She called sustained aesthetic improvement at 12 months for the filler in this study “really exciting.”
Dr. Green has reported financial relationships with numerous pharmaceutical companies. Dr. Tsao has reported financial relationships with Epiphany Dermatology, Lazarus AI, and UpToDate.
A version of this article first appeared on Medscape.com.
AT AAD 2022
New trial data show hair growth in more alopecia areata patients
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
BOSTON – according to updated results from two phase 3 trials presented at the annual meeting of the American Academy of Dermatology.
The results indicate improved response rates and hair growth among trial participants, said Brett King, MD, PhD, an associate professor of dermatology at Yale University, New Haven, Conn. He is the lead author of the analyses and presented the research.
Dr. King presented 36-week results from the clinical trials at the 2021 annual meeting of the European Academy of Dermatology and Venereology. The same results were also published March 26, 2022, in the New England Journal of Medicine.
“Every bit of data we’ve had is hugely important,” Dr. King said in an interview. “Every time we add 16 weeks of data across hundreds of patients, we are making a huge step forward toward the goal of [Food and Drug Administration approval for a medication for alopecia areata.”
All patients enrolled in the two trials, called BRAVE-AA1 and BRAVE-AA2, had severe alopecia areata, defined as a Severity of Alopecia Tool (SALT) score of at least 50, meaning 50% or less scalp coverage. The score ranges from 0 (no hair loss) to 100 (complete hair loss). The primary endpoint was a SALT score of 20 or less (80% scalp hair coverage).
The researchers pooled data from both clinical trials, with a combined enrollment of 1,200, for the 52-week results presented at the meeting. The placebo group stopped at 36 weeks, and these patients were randomly reassigned to either the 4-mg or 2-mg once-daily baricitinib treatment groups.
At baseline, patients enrolled in the trial had a mean SALT score of 85.5. After 52 weeks, 39.0% of patients who received 4 mg of baricitinib had at least 80% scalp coverage. Of this group, nearly three out of four (74.1%) had at least 90% scalp coverage, or a SALT score of 10 or less.
In patients who received 2 mg of baricitinib, 22.6% had a SALT score of 20 or less 20 (at least 80% scalp hair coverage) at 52 weeks, and two-thirds of that group (67.5%) had at least 90% scalp hair coverage at 52 weeks.
Comparatively, at 36 weeks, 35.2% of participants in BRAVE-AA1 and 32.5% of participants in BRAVE-AA2 receiving 4 mg of baricitinib had at least 80% scalp coverage. In the group taking the lower dose, 21.7% and 17.3% of patients in the BRAVE-AA1 and BRAVE-AA2 trials, respectively, had achieved at least 80% scalp coverage at 36 weeks. (These percentages differ slightly from the NEJM article because of a different analysis of missing data, Dr. King said. For comparison of both 36- and 52-week results, the percentages from the EADV are used above.)
The results indicate that 5% more patients reached the primary endpoint in the additional 16 weeks of the trial, Dr. King said.
Alopecia areata is an autoimmune condition where immune cells attack hair follicles, causing the hair to fall out, and is associated with emotional and psychological distress. Any hair follicle can be attacked, but they are rarely destroyed, so hair can regrow.
"Many underestimate the impact of this autoimmune hair loss condition," Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, told this news organization. He was not involved with the trial. "The burden of the disease, which certainly is an emotional but also a physical one, definitely needs to be addressed with indicated FDA-approved drugs," he noted, which is the goal of these trials.
The BRAVE-AA1 and BRAVE-AA2 trials focused on scalp hair regrowth.
Eyebrow and eyelash growth, secondary outcomes, also improved between 36 and 52 weeks in both groups, calculated using the proportion of participants who had achieved full regrowth or regrowth with minimal gaps. At 36 weeks, about 31%-35% of patients who received 4 mg of baricitinib regrew eyebrow and eyelash hair. By 52 weeks, more than two out of five patients regrew eyebrow (44.1%) and eyelash (45.3%) hair.
“It’s a fantastic achievement and a major step forward in alopecia areata, especially for patients with the most severe and refractory cases,” said Arash Mostaghimi, MD, MPH, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Mostaghimi is on the advisory board for Eli Lilly, which manufactures baricitinib, and Brigham and Women’s was one of the clinical sites of the trial.
While dermatologists have been aware of how JAK inhibitors can affect hair regrowth in alopecia patients, they have been using these drugs off label, Dr. Friedman said. Therefore, these drugs are expensive and more difficult to access. These trials provide "data that proves the efficacy and safety of [baricitinib] under the umbrella of the FDA portal," he added, which will hopefully lead to an approved indication for alopecia areata, so it can be more accessible to patients.
Adverse events at 52 weeks were consistent with data from 36 weeks, which found that none of these adverse events occurred in more than 10% of participants. The most common adverse events were headache, acne, and increases in muscle-related blood markers. The most common infections reported were pneumonia, herpes zoster, and urinary tract infection.
In February 2022, the FDA granted priority review for baricitinib for the treatment of severe alopecia areata. Lilly expects a regulatory decision by the end of 2022, they said in a press release.
Lilly provided funding for the BRAVE-AA1 and BRAVE-AA2 trials. Dr. King reported financial relationships with Aclaris, Arena Pharmaceuticals, Bristol-Myers Squibb, Concert Pharmaceutics, Dermavant, Lilly, Pfizer, Regeneron, Sanofi Genzyme, and Viela Bio. Dr. Mostaghimi has reported serving on an advisory board for Lilly. Dr. Friedman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
*This article was updated on 3/28/2022 to include Dr. Friedman's comments, and on 3/31/2022 to correct the statement regarding adverse events reported in the study
AT AAD 2022
Novel isotretinoin ointment for congenital ichthyosis shows promise
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
AT AAD 2022
COVID-19 infection linked to risk of cutaneous autoimmune and vascular diseases
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
BOSTON – . This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.
The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.
“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”
The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.
After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.
In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).
No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.
In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).
“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.
Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.
He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”
One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.
When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point."
Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.
* This story was updated on 3/29/22.
AT AAD 2022
Platelet-rich plasma for hair regrowth requires art and science
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
or administer the highly technique-dependent treatment, which creates plenty of room for suboptimal results, according to several experts at the annual meeting of the American Academy of Dermatology.
“The process is the product,” emphasized Terrence Keaney, MD, clinical associate professor at George Washington University, Washington, as well as cofounder of SkinDC, a private practice in Arlington, Va. He characterized PRP as a “growth factor cytokine cocktail,” for which relative benefits are fully dependent on the ingredients.
In other words, the efficacy of PRP is mostly dependent on the multiple steps in which blood drawn from a patient is separated into its components, processed to create a platelet-rich product, and then administered to the patient by injection or in conjunction with microneedles. While the goal is a platelet concentration two- to fivefold greater than that found in whole blood, this is not as straightforward as it sounds.
Many PRP device kits available
“There are a ton of [centrifuge] devices on the market and a lot of differences in the methodology in optimizing the platelet concentration,” Dr. Keaney explained. In addition, there are numerous proprietary collection tubes using different types of anticoagulants and different separator gels that also play a role in the goal of optimizing a platelet-rich and readily activated product.
“Recognize that each step in the preparation of PRP introduces a source of variation that affects the composition and efficacy of the final product,” said Steven Krueger, MD, who is completing his residency in dermatology at the University of Massachusetts, Worcester, but who has become an expert in the field. He contributed a chapter on this topic in the recently published book, Aesthetic Clinician’s Guide to Platelet Rich Plasma.
The importance of technique is reflected in inconsistent results from published controlled trials. Unfortunately, the authors of many studies have failed to provide details of their protocol. Ultimately, Dr. Krueger said this lack of clarity among available protocols has created a serious obstacle for establishing which steps are important and how to move the field forward.
Dr. Keaney agreed. Because of the frequent lack of details about how PRP was processed in available studies, the effort to draw conclusions about the experiences at different centers is like “comparing apples to oranges.”
“What is the ideal dose and concentrate? We don’t know,” Dr. Keaney said.
The first centrifuge device to receive regulatory approval was developed for orthopedic indications more than 20 years ago. There are now at least 20 centrifuge devices with 510K Food and Drug Administration clearance for separating blood components to produce PRP. The 510K designation means that they are “substantially equivalent” to an already approved device, but Dr. Krueger cautioned that their use in preparing PRP for treatment of hair loss remains off label.
Substandard devices are marketed
In the rapidly expanding world of PRP, there is also a growing array of PRP kits. Some of these kits have been cleared by the FDA but others have not. Dr. Krueger warned that collection tubes are being marketed that are substandard imitations of better-established products. He specifically cautioned against do-it-yourself PRP kits, which are likely to be less effective for isolating platelets and can also be contaminated with pyogenes that cause infection.
“Please use an FDA-cleared kit,” he said, warning that the risk of failing to do so is not just associated with lack of efficacy but also a significant risk of serious adverse events.
Of the centrifuge devices, both Dr. Krueger and Dr. Keaney generally recommend single-spin over double-spin devices, particularly at centers with a limited volume of PRP-based hair loss interventions. These are generally simpler.
Once the PRP has been properly prepared, the efficacy of PRP upon application can also be influenced by strategies for activation. Although the exact mechanism of PRP in stimulating hair growth is incompletely defined, the role of platelets in releasing growth factors is believed to be critical. There are a number of methods to stimulate platelets upon administration, such as exposure to endogenous collagen or thrombin or exogenous chemicals, such as calcium chloride, but again, techniques differ and the optimal approach is unknown.
One concern is the recent and largely unregulated growth of regenerative cell and tissue products for treating a large array of clinical disorders or cosmetic issues, according to Dr. Keaney. He warned of a “wild, wild west mentality” that has attracted providers with inadequate training and experience. In turn, this is now attracting the attention of the FDA as well as those involved in enforcing FDA directives.
“There is definitely more scrutiny of regenerative products,” he said, noting that he is careful about how he markets PRP. While it is reasonable to offer this off-label treatment as an in-office procedure, he noted that it is illegal to advertise off-label products. He reported that he has become more prudent when including this option among hair regrowth services provided in his practice.
Omer E. Ibrahim, MD, a dermatologist affiliated with Chicago Cosmetic Surgery and Dermatology, agreed. While he also feels there is good evidence to support PRP as a hair loss treatment option, particularly for androgenic alopecia, he also expressed caution about promoting this approach in exclusion of other options.
“Patients ask me for a PRP consultation, but there is no such thing as a PRP consultation in my practice,” Dr. Ibrahim said. He incorporates PRP into other strategies. “I stress that it is one part of a multipronged approach,” he added.
Dr. Ibrahim has reported financial relationships with Alastin Skincare, Allergan, Eclipse Medical, Galderma USA, and Revision Skincare. Dr. Keaney has reported financial relationships with Allergan, DermTech, Evolus, Galderma USA, Merz Aesthetics, Revance Therapeutics, and Syneron Candela. Dr. Krueger has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Topical options for treating melasma continue to expand
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
BOSTON – In the opinion of Seemal R. Desai, MD, dermatologists are obligated to tell their patients with melasma that their condition is a chronic disease with no cure.
“We have to set expectations upfront, because you all know the history,” Dr. Desai, founder and medical director of Innovative Dermatology in Dallas, said at the annual meeting of the American Academy of Dermatology. “You get someone better, their melasma gets lighter, and then they’re lost to follow-up for a year. Then they’re back to your office after that beach vacation because their melasma has come back with a vengeance because they were out in the sun too much. We have to tell our patients that melasma therapy is a journey of skin lightening but it’s not going to be a one-stop shop of getting it completely cured.”
As for treatment of melasma, “hydroquinone is still our workhorse, our gold standard.” Dr. Desai said. “I tell patients, ‘I’m going to keep you on it for 16 weeks. Then you’re going to come back. I’m going to see where you are, and we’ll move into the nonhydroquinone therapies once your disease is under control.’ ”
However, new therapies for melasma are needed because long-term use of hydroquinone can lead to complications such as ochronosis, nail discoloration, conjunctival melanosis, and corneal degeneration.
Emerging treatments
. Dr. Desai described azelaic acid as his “go to” nonhydroquinone option for skin lightening. In one study, 20% azelaic acid was used twice daily in 155 patients with facial melasma. Of these, 73% showed improvement after 6 months of therapy. Side effects were minimal and included erythema, pruritus, and burning.
Another option is topically compounded methimazole, a potent peroxidase inhibitor that causes morphologic change in melanocytes. “You can get it compounded as a 5% cream,” he said of the antithyroid agent. “It’s not that expensive, and even high concentrations are not melanocytotoxic. There’s minimal systemic absorption because the molecule is large, so there really is not any effect on TSH [thyroid-stimulating hormone] or T4 levels.”
Kojic acid dipalmitate, an antibiotic produced by many species of Aspergillus and Penicillium, can also be used as a second-line melasma treatment. Unlike kojic acid, kojic acid dipalmitate is more stable to light, heat, pH, and oxidation, and is also compatible with most organic sunscreens. It works by inhibiting tyrosinase. “It’s already available overseas and will soon be available in the U.S. as a derivative of kojic acid,” he said.
There is also vitamin C serum, which reduces tyrosinase activity via an antioxidant effect. “When you combine it with azelaic acid or sunscreen, vitamin C helps to augment the response,” Dr. Desai said. In one study that compared 5% ascorbic acid with 4% hydroquinone, 62.5% vs. 93% of patients improved, respectively, but side effects were more prominent in those who received 4% hydroquinone (68.7% vs. 6.2%).
An additional off-label option for melasma is oral tranexamic acid, which controls pigmentation by inhibiting the release of inflammatory mediators, specifically prostaglandins and arachidonic acid, which are involved in melanogenesis.
Dr. Desai often uses a dose of 325 mg twice daily. “Think of tranexamic acid as an anti-inflammatory,” he said. Tranexamic acid is contraindicated in patients who are currently taking or have previously taken anticoagulant medications; those who are pregnant or breastfeeding, or are smokers; and in those with renal, cardiac, and/or pulmonary disease. It has a half-life of about 7.5 hours, so the twice daily dosing “is quite effective,” he said.
“Do I leave my patients on this for years at a time to see if it’s going to work? No. When this works in treating melasma it works very quickly. I tell patients they’re going to see results in the first 8-12 weeks. That’s the beauty of using this orally.”
Another emerging therapy is Rubus occidentalis (black raspberry), a botanical-based ingredient in a 3% topical suspension that was compared with 4% hydroquinone in a randomized placebo-controlled trial. In the study, efficacy of Rubus occidentalis was considered comparable to that of hydroquinone. “This not only blocks melanogenesis, it also helps to block melanosome transfer,” said Dr. Desai, who is a past president of the Skin of Color Society.
Another natural option for melasma patients is topical cysteamine, which is the simplest aminothiol physiologically produced in human cells from the essential amino acid cysteine. “This is great for patients with recalcitrant disease, or for patients who, after 12-16 weeks of hydroquinone, you want them to have a break. I use it as a 5% concentration, and it works nicely,” he said. Cysteamine is also highly concentrated in human milk.
Dr. Desai disclosed that he performs clinical trials and consulting for many companies including L’Oréal, Galderma, Allergan, and AbbVie.
AT AAD 2022