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Atopic dermatitis, sleep difficulties often intertwined
According to Phyllis C. Zee, MD, PhD, proinflammatory cytokines influence neural processes that affect sleep and circadian rhythm. “It’s almost like when you’re most vulnerable, when you’re sleeping, the immune system is kind of poised for attack,” Dr. Zee, chief of the division of sleep medicine at Northwestern University, Chicago, said at the Revolutionizing Atopic Dermatitis symposium. “This is normal, and perhaps in some of these inflammatory disorders, it’s gone a little haywire.”
Circulation of interleukins and cytokines are high in the morning, become lower in the afternoon, and then get higher again in the evening hours and into the night during sleep, she continued. “Whereas if you look at something like blood flow, it increases on a diurnal basis,” she said. “It’s higher during the day and a little bit lower during the mid-day, and a little bit higher during the evening. That parallels changes in the sebum production of the skin and the transepidermal water loss, which has been implicated in some of the symptoms of AD. What’s curious about this is that the transdermal/epidermal water loss is really highest during the sleep period. Some of this is sleep gated, but some of this is circadian gated as well. There’s a bidirectional relationship between sleep and immunity.”
Disturbance of sleep can have multiple consequences. It can activate the hypothalamic-pituitary-adrenal axis through autonomic activation, increase brain metabolic activity, trigger mood disturbances and cognitive impairment, and cause daytime sleepiness and health consequences that affect cardiometabolic and immunologic health.
One study conducted by Anna B. Fishbein, MD, Dr. Zee, and colleagues at Northwestern examined the effects of sleep duration and sleep disruption and movements in 38 children with and without moderate to severe AD. It found that children with AD get about 1 hour less of sleep per night overall, compared with age-matched healthy controls. “It’s not so much difficulty falling asleep, but more difficulty staying asleep as determined by wake after sleep onset,” said Dr. Zee, who is also a professor of neurology at Northwestern.
A study of 34,613 adults who participated in the 2012 National Health and Nutrition Examination Survey found that eczema increased the odds of fatigue (odds ratio, 2.97), daytime sleepiness (OR, 2.66), and regular insomnia (OR, 2.36).
“Very importantly, it predicted poor health,” said Dr. Zee, who was one of the study’s coauthors. “This gives us an opportunity to think about how we can improve sleep to improve outcomes.”
Dr. Zee advises dermatologists and primary care clinicians to ask patients with AD about their sleep health by using a screening tool such as the self-reported STOP questionnaire, which consists of the following questions: “Do you snore loudly?” “Do you often feel tired, fatigued, or sleepy during daytime?” “Has anyone observed you stop breathing during your sleep?” “Do you have or are you being treated for high blood pressure?”
Other clinical indicators of a sleep disorder, such as obstructive sleep apnea (OSA), include having a neck circumference of 17 inches or greater in men and 16 inches or greater in women. “You want to also do a brief upper-airway examination, the Mallampati classification where you say to the patient, ‘open your mouth, don’t stick your mouth out too much,’ and you look at how crowded the upper airway is,” Dr. Zee said . “Someone with a Mallampati score of 3 has a very high risk of having sleep apnea.”
She also recommends asking patients with AD if they have difficulty falling asleep or staying asleep 3 or more nights per week, and about the frequency and duration of awakenings. “Maybe they have insomnia as a disorder,” she said. “If they have trouble falling asleep, maybe they have a circadian rhythm disorder. You want to ask about snoring, choking, and stop breathing episodes, because those are symptoms of sleep apnea. You want to ask about itch, uncomfortable sensations in the limbs during sleep or while trying to get to sleep, because that may be something like restless legs syndrome. Sleep disorder assessment is important because it impair daytime function, cognition, attention, and disruptive behavior, especially in children.”
For the management of insomnia, try behavioral approaches first. “You don’t want to try medications from the get-go,” Dr. Zee advised. Techniques include sleep hygiene and stimulus control therapy, “to make the bedroom a safe place to sleep. Lower the temperature a little bit and get rid of the allergens as much as possible. Relaxation and cognitive-behavioral therapy can also help. If you get a lot of light during the day, structure your physical activity, and watch what and when you eat.”
An OSA diagnosis requires evaluation of objective information from a sleep study. Common treatments of mild to moderate OSA include nasal continuous positive airway pressure and oral appliances.
Dr. Zee disclosed that she had received research funding from the National Institutes of Health, Jazz Pharmaceuticals, Harmony and Apnimed. She also serves on the scientific advisory board of Eisai, Jazz, CVS-Caremark, Takeda, and Sanofi-Aventis, and holds stock in Teva.
According to Phyllis C. Zee, MD, PhD, proinflammatory cytokines influence neural processes that affect sleep and circadian rhythm. “It’s almost like when you’re most vulnerable, when you’re sleeping, the immune system is kind of poised for attack,” Dr. Zee, chief of the division of sleep medicine at Northwestern University, Chicago, said at the Revolutionizing Atopic Dermatitis symposium. “This is normal, and perhaps in some of these inflammatory disorders, it’s gone a little haywire.”
Circulation of interleukins and cytokines are high in the morning, become lower in the afternoon, and then get higher again in the evening hours and into the night during sleep, she continued. “Whereas if you look at something like blood flow, it increases on a diurnal basis,” she said. “It’s higher during the day and a little bit lower during the mid-day, and a little bit higher during the evening. That parallels changes in the sebum production of the skin and the transepidermal water loss, which has been implicated in some of the symptoms of AD. What’s curious about this is that the transdermal/epidermal water loss is really highest during the sleep period. Some of this is sleep gated, but some of this is circadian gated as well. There’s a bidirectional relationship between sleep and immunity.”
Disturbance of sleep can have multiple consequences. It can activate the hypothalamic-pituitary-adrenal axis through autonomic activation, increase brain metabolic activity, trigger mood disturbances and cognitive impairment, and cause daytime sleepiness and health consequences that affect cardiometabolic and immunologic health.
One study conducted by Anna B. Fishbein, MD, Dr. Zee, and colleagues at Northwestern examined the effects of sleep duration and sleep disruption and movements in 38 children with and without moderate to severe AD. It found that children with AD get about 1 hour less of sleep per night overall, compared with age-matched healthy controls. “It’s not so much difficulty falling asleep, but more difficulty staying asleep as determined by wake after sleep onset,” said Dr. Zee, who is also a professor of neurology at Northwestern.
A study of 34,613 adults who participated in the 2012 National Health and Nutrition Examination Survey found that eczema increased the odds of fatigue (odds ratio, 2.97), daytime sleepiness (OR, 2.66), and regular insomnia (OR, 2.36).
“Very importantly, it predicted poor health,” said Dr. Zee, who was one of the study’s coauthors. “This gives us an opportunity to think about how we can improve sleep to improve outcomes.”
Dr. Zee advises dermatologists and primary care clinicians to ask patients with AD about their sleep health by using a screening tool such as the self-reported STOP questionnaire, which consists of the following questions: “Do you snore loudly?” “Do you often feel tired, fatigued, or sleepy during daytime?” “Has anyone observed you stop breathing during your sleep?” “Do you have or are you being treated for high blood pressure?”
Other clinical indicators of a sleep disorder, such as obstructive sleep apnea (OSA), include having a neck circumference of 17 inches or greater in men and 16 inches or greater in women. “You want to also do a brief upper-airway examination, the Mallampati classification where you say to the patient, ‘open your mouth, don’t stick your mouth out too much,’ and you look at how crowded the upper airway is,” Dr. Zee said . “Someone with a Mallampati score of 3 has a very high risk of having sleep apnea.”
She also recommends asking patients with AD if they have difficulty falling asleep or staying asleep 3 or more nights per week, and about the frequency and duration of awakenings. “Maybe they have insomnia as a disorder,” she said. “If they have trouble falling asleep, maybe they have a circadian rhythm disorder. You want to ask about snoring, choking, and stop breathing episodes, because those are symptoms of sleep apnea. You want to ask about itch, uncomfortable sensations in the limbs during sleep or while trying to get to sleep, because that may be something like restless legs syndrome. Sleep disorder assessment is important because it impair daytime function, cognition, attention, and disruptive behavior, especially in children.”
For the management of insomnia, try behavioral approaches first. “You don’t want to try medications from the get-go,” Dr. Zee advised. Techniques include sleep hygiene and stimulus control therapy, “to make the bedroom a safe place to sleep. Lower the temperature a little bit and get rid of the allergens as much as possible. Relaxation and cognitive-behavioral therapy can also help. If you get a lot of light during the day, structure your physical activity, and watch what and when you eat.”
An OSA diagnosis requires evaluation of objective information from a sleep study. Common treatments of mild to moderate OSA include nasal continuous positive airway pressure and oral appliances.
Dr. Zee disclosed that she had received research funding from the National Institutes of Health, Jazz Pharmaceuticals, Harmony and Apnimed. She also serves on the scientific advisory board of Eisai, Jazz, CVS-Caremark, Takeda, and Sanofi-Aventis, and holds stock in Teva.
According to Phyllis C. Zee, MD, PhD, proinflammatory cytokines influence neural processes that affect sleep and circadian rhythm. “It’s almost like when you’re most vulnerable, when you’re sleeping, the immune system is kind of poised for attack,” Dr. Zee, chief of the division of sleep medicine at Northwestern University, Chicago, said at the Revolutionizing Atopic Dermatitis symposium. “This is normal, and perhaps in some of these inflammatory disorders, it’s gone a little haywire.”
Circulation of interleukins and cytokines are high in the morning, become lower in the afternoon, and then get higher again in the evening hours and into the night during sleep, she continued. “Whereas if you look at something like blood flow, it increases on a diurnal basis,” she said. “It’s higher during the day and a little bit lower during the mid-day, and a little bit higher during the evening. That parallels changes in the sebum production of the skin and the transepidermal water loss, which has been implicated in some of the symptoms of AD. What’s curious about this is that the transdermal/epidermal water loss is really highest during the sleep period. Some of this is sleep gated, but some of this is circadian gated as well. There’s a bidirectional relationship between sleep and immunity.”
Disturbance of sleep can have multiple consequences. It can activate the hypothalamic-pituitary-adrenal axis through autonomic activation, increase brain metabolic activity, trigger mood disturbances and cognitive impairment, and cause daytime sleepiness and health consequences that affect cardiometabolic and immunologic health.
One study conducted by Anna B. Fishbein, MD, Dr. Zee, and colleagues at Northwestern examined the effects of sleep duration and sleep disruption and movements in 38 children with and without moderate to severe AD. It found that children with AD get about 1 hour less of sleep per night overall, compared with age-matched healthy controls. “It’s not so much difficulty falling asleep, but more difficulty staying asleep as determined by wake after sleep onset,” said Dr. Zee, who is also a professor of neurology at Northwestern.
A study of 34,613 adults who participated in the 2012 National Health and Nutrition Examination Survey found that eczema increased the odds of fatigue (odds ratio, 2.97), daytime sleepiness (OR, 2.66), and regular insomnia (OR, 2.36).
“Very importantly, it predicted poor health,” said Dr. Zee, who was one of the study’s coauthors. “This gives us an opportunity to think about how we can improve sleep to improve outcomes.”
Dr. Zee advises dermatologists and primary care clinicians to ask patients with AD about their sleep health by using a screening tool such as the self-reported STOP questionnaire, which consists of the following questions: “Do you snore loudly?” “Do you often feel tired, fatigued, or sleepy during daytime?” “Has anyone observed you stop breathing during your sleep?” “Do you have or are you being treated for high blood pressure?”
Other clinical indicators of a sleep disorder, such as obstructive sleep apnea (OSA), include having a neck circumference of 17 inches or greater in men and 16 inches or greater in women. “You want to also do a brief upper-airway examination, the Mallampati classification where you say to the patient, ‘open your mouth, don’t stick your mouth out too much,’ and you look at how crowded the upper airway is,” Dr. Zee said . “Someone with a Mallampati score of 3 has a very high risk of having sleep apnea.”
She also recommends asking patients with AD if they have difficulty falling asleep or staying asleep 3 or more nights per week, and about the frequency and duration of awakenings. “Maybe they have insomnia as a disorder,” she said. “If they have trouble falling asleep, maybe they have a circadian rhythm disorder. You want to ask about snoring, choking, and stop breathing episodes, because those are symptoms of sleep apnea. You want to ask about itch, uncomfortable sensations in the limbs during sleep or while trying to get to sleep, because that may be something like restless legs syndrome. Sleep disorder assessment is important because it impair daytime function, cognition, attention, and disruptive behavior, especially in children.”
For the management of insomnia, try behavioral approaches first. “You don’t want to try medications from the get-go,” Dr. Zee advised. Techniques include sleep hygiene and stimulus control therapy, “to make the bedroom a safe place to sleep. Lower the temperature a little bit and get rid of the allergens as much as possible. Relaxation and cognitive-behavioral therapy can also help. If you get a lot of light during the day, structure your physical activity, and watch what and when you eat.”
An OSA diagnosis requires evaluation of objective information from a sleep study. Common treatments of mild to moderate OSA include nasal continuous positive airway pressure and oral appliances.
Dr. Zee disclosed that she had received research funding from the National Institutes of Health, Jazz Pharmaceuticals, Harmony and Apnimed. She also serves on the scientific advisory board of Eisai, Jazz, CVS-Caremark, Takeda, and Sanofi-Aventis, and holds stock in Teva.
FROM REVOLUTIONIZING AD 2020
What drives treatment satisfaction among adults with atopic dermatitis?
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
.
Satisfaction scores were higher when specialists prescribed systemic therapy, but were lower when nonspecialists prescribed systemic therapy and when specialists prescribed only topical therapy.
Those are among key findings from an analysis of the Medical Expenditure Panel Surveys reported by Brian T. Cheng during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“AD management is complex,” said Mr. Cheng, a medical student at Northwestern University, Chicago. “It includes patient education about trigger avoidance, over-the-counter and prescription topical therapies, as well as systemic therapies. Previous studies have shown major decrements to quality of life as well as atopic and non-atopic comorbidities in these patients. The burden of AD and their comorbidities, as well as their management, may impact patient satisfaction.”
Prior studies have demonstrated that patient satisfaction is associated with improvements in clinical outcomes, increased patient retention, and reduced malpractice claims (Br J Dermatol. 2001 Oct;145[4]:617-23, Arch Dermatol 2008 Feb;144[2]:263-5). However, since data on patient satisfaction in AD are limited, Mr. Cheng and the study’s senior author, Jonathan I. Silverberg, MD, PhD, MPH, set out to examine overall patient satisfaction among adults with AD, to determine associations of patient satisfaction with patterns of health care utilization, and to identify predictors of higher satisfaction among these adults.
The researchers conducted a cross-sectional retrospective analysis of 3,810 patients from the 2000-2015 Medical Expenditure Panel Surveys, representative surveys of the U.S. noninstitutionalized population conducted annually by the Agency for Healthcare Research and Quality. They used ICD-9 codes 691 and 692 to determine AD diagnosis and five Consumer Assessment of Health Plans Survey (CAHPS) questions to assess patients’ satisfaction with their clinicians. “These questions have been extensively validated to correlate with global satisfaction,” Mr. Cheng said. “These are not disease-specific and allow for comparison across multiple diseases.”
Next, the researchers created a composite satisfaction score based on the methods of Anthony Jerant, MD, of the University of California, Davis, and colleagues. They adjusted each question in the CAHPS survey to have an equal weight and then summed these into a composite satisfaction score. “We examined patient satisfaction comparing across diseases, and based on the guidelines from the AHRQ to isolate that impact of patient-physician interaction, we adjusted for sociodemographics, mental and physical health status, self-reported health rating, as well as multimorbidity and comorbid diseases.”
Compared with adults who are healthy, adults with AD had lower patient satisfaction overall. “Moreover, people with AD had lower satisfaction compared to those with psoriasis, which may reflect more substantial itch burden as well as the greater comorbid disease challenges in management,” Mr. Cheng said. “It may also reflect the renaissance in psoriasis treatment over the last 10-20 years, giving a wider spectrum of treatment and thus a higher patient satisfaction.”
Among adults with AD, lower satisfaction was consistent across all domains of CAHPS. For the question of “How often health providers listen carefully to you” the adjusted OR (aOR) was 0.87 (P = .008). For the question of “How often health providers explain things in a way that was easy to understand” the aOR was 0.89 (P = .003). For the question of “How often health providers spent enough time with you” the aOR was 0.86 (P = .0001). For “How often providers showed respect for what you had to say” the aOR was 0.91 (P = .02).
Recognizing that treatment regimens are complex and used differently by provider type, the researchers examined interactions between specialists (dermatologists and allergists) and treatment type. “Previous studies found dermatologists treat more severe, chronic AD,” Mr. Cheng said. “We found here that there was lower satisfaction among those treated with topical therapy and by specialists, which may reflect inadequate disease control. We also found lower satisfaction among those treated with systemic therapy by primary care physicians. This may reflect that these patients are not achieving optimal therapy. We found that satisfaction was highest among those treated with systemic therapy and by dermatologists and allergists.”
Socioeconomic, racial/ethnic, and health care disparities were observed in terms of satisfaction among this cohort. The following characteristics were significantly associated with lower patient satisfaction, compared with the general cohort of adults with AD: poor to low income (aOR, –1.82; P less than .0001), multiracial/other race (aOR, –2.34; P = .0001), Hispanic ethnicity (aOR, –1.40; P = .007), and having no insurance coverage (aOR, –4.53; P less than .0001).
“Moreover, those with multimorbidity had even lower satisfaction,” Mr. Cheng said. “In previous studies, AD has been linked with many other comorbidities. This may reflect that these patients are not being adequately managed overall. So, there’s a need here for multidisciplinary care to ensure that all of these comorbidities and the full spectrum of symptoms are being managed adequately.”
He concluded that future research is needed to determine strategies to optimize patient satisfaction in adults with AD.
“I’m not sure how much more provocative you can get in terms of data,” added Dr. Silverberg, director of clinical research and contact dermatitis at George Washington University, Washington. “It’s really eye-opening. I think many clinicians may feel like they’re doing a perfect job in managing this disease. These data suggest that at least at the national level that may not be the case.”
Mr. Cheng reported having no financial disclosures. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
FROM REVOLUTIONIZING AD 2020
Severe atopic dermatitis often puts a dent in quality of life
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
In his role as head of the division of pediatric behavioral health at National Jewish Health, Denver, Bruce G. Bender, PhD, helps children and adults navigate the adverse effects of severe atopic dermatitis (AD) on their quality of life.
“There have been many surveys of adults with AD who report impairment of their sleep, reduced activity level, increased work absence, financial burden, emotional distress, and social avoidance,” he said at the Revolutionizing Atopic Dermatitis virtual symposium. “Similarly, children with AD or their parents report emotional distress, reduced activity, and increased school absence, social avoidance, and sleep disturbance. Families report financial burdens, conflict, particularly among the adults, social avoidance, sleep disturbance in the parents, and reduction of well-being in the siblings.”
In an effort to objectively measure sleep change in this population, Dr. Bender and colleagues recruited 14 adults with AD and 14 healthy controls who wore an ActiGraph for 1 week and completed questionnaires about sleep, itch, and quality of life. Patients with AD were awake almost twice as many minutes each night as the healthy controls (a mean of 57.3 vs. 32.3 minutes, respectively; P = .0480). Consequently, their sleep efficiency was significantly reduced based on the Pittsburgh sleep quality index (a mean of 90.6 vs. 95; P = .0305).
In another study, Dr. Bender and colleagues enrolled 20 adults with AD who underwent 2 nights of polysomnography and actigraphy. The lab was set up to measure a scratching event, which was recorded when a burst of electromyographic activity of at least 3 seconds was accompanied by a visible scratching motion. “We learned that sleep efficiency as measured by both PSG and actigraphy correlated with total body surface area and scratching index,” he said. “As we might assume, the more skin involved, the more patients scratch, the less well they sleep.”
Behavioral, neurocognitive effects
In a separate study of AD, sleep, and behavior, the researchers studied 1,041 children with asthma who were enrolled in the Childhood Asthma Management Program at eight North American sites. They used baseline parent ratings on standardized sleep and behavior rating scales and found that increased awakenings were associated with increased school absence and daytime behavior problems. “So, not only do children with AD sleep less well, but this shows up to impair their functioning during the day,” said Dr. Bender, professor of psychiatry at the University of Colorado, Denver.
In a report from Australia, researchers set out to explore the association between sleep and neurocognitive function in 21 children with eczema and 20 healthy controls. Participants underwent cognitive testing and polysomnography. The authors found that the children with eczema demonstrated lower test scores. Reduced scores were correlated with parental reports of sleep problems but not polysomnography.
In a much larger study funded by the Agency for Healthcare Research and Quality, investigators analyzed data on 354,416 children and 34,613 adults from 19 U.S. population surveys including the National Health Interview Survey 1997-2013 and the National Survey of Children’s Health 2003/4 and 2007/8. They found that AD was associated with ADHD in children (adjusted odds ratio, 1.14) and adults (aOR, 1.61). Higher odds of ADHD were found in children who had significant sleep disturbance (aOR, 16.83) and other allergic disease and asthma (aOR, 1.61).
“All of these findings show that AD can impact quality of life, especially sleep, with the result of poorer daytime functioning,” Dr. Bender said. “But those studies don’t answer this question: Are patients with AD at increased risk for psychological disorders such as depression and anxiety?”
Impact on depression, anxiety
Two systematic reviews on the topic suggest that patients with AD are twice as likely to experience depression. One was published in 2018 and the other in 2019. The 2018 review reported a little more than a twofold increase (OR, 2.19), the 2019 review a little bit less (OR, 1.71).
“At the more severe end of the depression continuum, we sometimes see suicidal ideation and suicide attempts,” Dr. Bender said. “A number of studies have asked whether these are increased in patients with AD. Quite a few studies collectively show an increased incidence of suicidal ideation. The question of suicide attempts is reflected in fewer studies. And while the result is small, it is significant. There is a significant increase reported of suicide attempts in AD patients.”
The 2018 review also found an increased incidence of anxiety in AD patients: a little more than twofold in adults (OR, 2.19) and a little less than twofold in children (OR, 1.81).
“It’s a two-way relationship between AD and psychological factors,” Dr. Bender said. “We generally think about AD – the stress that it brings, the burden that it puts on children, adults, and families. But it can work the other way around,” he said, referring to patients who have psychological problems, experience a great deal of stress, have trouble being adherent to their treatment regimen, and find it difficult to resist scratching. “The behavioral/psychological characteristics of the patient also drive the AD. It is well established that acute and chronic stress can result in a worsening of skin conditions in AD patients.”
Behavioral health interventions that have been described in the literature include cognitive therapy, stress management, biofeedback, hypnotherapy, relaxation training, mindfulness, habit reversal, and patient education – some of which have been tested in randomized trials. “All of them report a decrease in scratching as a consequence of the behavioral intervention,” Dr. Bender said.
“Other studies have been reported that look at the impact of behavioral interventions on the severity of the skin condition. Most report an improvement in the skin condition from these behavioral interventions but it’s not a perfect literature.” Critiques of these studies include the fact that there is often not enough detail about the intervention or the framework for the intervention that would allow a clinician to test an intervention in another study or actually pull that intervention into clinical practice (Cochrane Database Syst Rev. 2014 Jan 7;2014[1]:CD004054), (Int Arch Allergy Immunol.2007;144[1]:1-9).
“Some of the studies lack rigorous designs, some have sampling bias, and some have inadequate outcome measurements,” he said. “We really need additional, high-quality studies to look at what is helpful for patients with AD.”
Dr. Bender reported having no financial disclosures.
FROM REVOLUTIONIZING AD 2020
Data on atopic dermatitis risk factors are accumulating
, according to Zelma Chiesa Fuxench, MD.
This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.
“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
Environmental factors
Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”
As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.
“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”
A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.
In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.
Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.
Probiotics
The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”
In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
Antibiotic exposure
What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”
In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
Prevention strategies
Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.
Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.
However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.
For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.
She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”
Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.
, according to Zelma Chiesa Fuxench, MD.
This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.
“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
Environmental factors
Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”
As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.
“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”
A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.
In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.
Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.
Probiotics
The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”
In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
Antibiotic exposure
What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”
In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
Prevention strategies
Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.
Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.
However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.
For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.
She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”
Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.
, according to Zelma Chiesa Fuxench, MD.
This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.
“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
Environmental factors
Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”
As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.
“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”
A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.
In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.
Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.
Probiotics
The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”
In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
Antibiotic exposure
What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”
In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
Prevention strategies
Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.
Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.
However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.
For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.
She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”
Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.
FROM REVOLUTIONIZING AD 2020
Are pediatric and adult dermatitis the same disease?
“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.
Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.
Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.
Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”
AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).
Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).
Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”
AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).
According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”
Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.
Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.
Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.
Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”
AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).
Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).
Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”
AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).
According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”
Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.
Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.
Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.
Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”
AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).
Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).
Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”
AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).
According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”
Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
FROM REVOLUTIONIZING AD 2020
Bathing now more widely accepted as an eczema treatment strategy
According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.
During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.
“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”
In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.
“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.
She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”
Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).
Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”
A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.
“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”
In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”
In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.
In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.
“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”
Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.
According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.
During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.
“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”
In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.
“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.
She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”
Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).
Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”
A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.
“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”
In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”
In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.
In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.
“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”
Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.
According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.
During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.
“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”
In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.
“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.
She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”
Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).
Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”
A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.
“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”
In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”
In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.
In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.
“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”
Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.
FROM REVOLUTIONIZING AD 2020
Daily moisturizers a bedrock of atopic dermatitis management
Mounting .
In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.
Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:
1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.
2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.
3. It promotes a healthy microbiome via induction of antimicrobial peptides.
4. It maintains stratum corneum acidification, which protects against pathogens.
5. It reduces recurrence of flares when used daily.
6. It prevents the onset of AD when applied early in life to at-risk children.
A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”
In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.
“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”
With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”
Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”
A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”
She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.
Mounting .
In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.
Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:
1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.
2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.
3. It promotes a healthy microbiome via induction of antimicrobial peptides.
4. It maintains stratum corneum acidification, which protects against pathogens.
5. It reduces recurrence of flares when used daily.
6. It prevents the onset of AD when applied early in life to at-risk children.
A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”
In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.
“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”
With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”
Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”
A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”
She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.
Mounting .
In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.
Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:
1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.
2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.
3. It promotes a healthy microbiome via induction of antimicrobial peptides.
4. It maintains stratum corneum acidification, which protects against pathogens.
5. It reduces recurrence of flares when used daily.
6. It prevents the onset of AD when applied early in life to at-risk children.
A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”
In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.
“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”
With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”
Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”
A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”
She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”
Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.
FROM REVOLUTIONIZING AD 2020
Baseline body surface area may drive optimal baricitinib responses
results from an analysis of phase 3 data showed.
“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.
Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.
“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”
The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.
Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”
On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.
When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.
“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”
The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.
results from an analysis of phase 3 data showed.
“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.
Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.
“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”
The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.
Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”
On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.
When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.
“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”
The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.
results from an analysis of phase 3 data showed.
“This proposed clinical tailoring approach for baricitinib 2 mg allows for treatment of patients who are more likely to respond to therapy and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg,” Eric L. Simpson, MD, said during a late-breaking abstract session at the Revolutionizing Atopic Dermatitis virtual symposium.
Baricitinib is an oral, reversible and selective Janus kinase 1/JAK2 inhibitor that is approved in Europe for the treatment of moderate to severe AD in adults who are candidates for systemic therapy. In the United States, it is approved for treating rheumatoid arthritis, and is currently under Food and Drug Administration review in the United States for AD.
For the current analysis, Dr. Simpson, professor of dermatology at Oregon Health & Science University, Portland, and colleagues set out to identify responders to baricitinib 2 mg using a tailored approach based on baseline BSA affected and early clinical improvement in the phase 3 monotherapy trial BREEZE-AD5. The trial enrolled 440 patients: 147 to placebo, 147 to baricitinib 1 mg once daily, and 146 to baricitinib 2 mg once daily. The primary endpoint was Eczema Area and Severity Index (EASI)–75 at week 16.
“Understanding which patients can benefit most from this treatment was our goal,” Dr. Simpson said. “By tailoring your therapy, you can significantly improve the patient experience, increase the cost-effectiveness of a therapy, and you can ensure that only patients who are likely to benefit are exposed to a drug.”
The researchers used a classification and regression tree algorithm that identified baseline BSA as the strongest predictor of EASI-75 response at week 16. A BSA cutoff of 50% was established as the optimal cutoff for sensitivity and negative predictive value. Results for EASI-75 and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) scores of 0 or 1 were confirmed using a BSA of 10%-50% at baseline to predict response, compared with a BSA or greater than 50% at baseline.
Sensitivity analyses revealed that about 90% of patients with an EASI-75 response were in the BSA 10%-50% group. Conversely, among patients with a BSA greater than 50%, the negative predictive value was greater than 90%, “so there’s a 90% chance you’re not going to hit that EASI-75 at week 16 if your BSA is greater than 50%,” Dr. Simpson explained. “The same holds true for vIGA-AD, so that 50% cutoff is important for understanding whether someone is going to respond or not.”
On the EASI-75, 38% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 10% in the BSA greater than 50% group. A similar association was observed on the vIGA-AD, where 32% of patients in the BSA 10%-50% group responded to baricitinib at week 16, compared with 5% in the BSA greater than 50% group.
When stratified by early response assessed at week 4, based on a 4-point improvement or greater on the Itch Numeric Rating Scale, 55% of those patients became EASI-75 responders, compared with 17% who were not. A similar association was observed by early response assessed at week 8.
“Due to the rapid onset of response, clinical assessment of patients after 4-8 weeks of initiation of baricitinib 2 mg treatment provided a positive feedback to patients who are likely to benefit from long-term therapy,” Dr. Simpson said. “This analysis may allow for a precision-medicine approach to therapy in moderate to severe AD.”
The study was supported by Eli Lilly, and was under license from Incyte. Dr. Simpson reported serving as an investigator for and consultant to numerous pharmaceutical companies.
FROM REVOLUTIONIZING AD 2020
Avoiding atopic dermatitis triggers easier said than done
“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”
He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).
“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”
AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”
In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.
Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.
Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”
High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.
Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”
In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.
Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”
Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”
Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”
Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”
In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”
Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.
PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”
He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).
“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”
AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”
In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.
Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.
Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”
High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.
Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”
In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.
Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”
Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”
Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”
Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”
In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”
Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.
PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
“Guidelines on trigger avoidance are written as if it’s easy to do,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis virtual symposium. “It turns out that trigger avoidance is really complicated.”
He and his colleagues conducted a study of most common triggers for itch based on a prospective dermatology practice–based study of 587 adults with AD . About two-thirds (65%) reported one or more itch trigger in the past week and 36% had three or more itch triggers in the past week. The two most common triggers were stress (35%) and sweat (31%).
“To me, this is provocative, because this is not how I was trained in residency,” said Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington. “I was trained that it’s all about excess showering, dry air, or cold temperature. Those are important, but the most common triggers are stress and sweat.”
AD triggers are also commonly linked to seasonality. “If you ask patients when their AD is worse, sometimes it’s winter,” he said. “Sometimes it’s spring. Sometimes it’s summer. It turns out that there is a distinct set of triggers that are associated with AD seasonality.” Wintertime worsening of disease is associated with cold temperature and weather change, he continued, while springtime worsening of disease is often linked to weather change and dry air. Common summertime triggers for flares include hot temperature, heat, sweat, weather change, sunlight, humid air, and dry air. “In the fall, the weather change again comes up as a trigger. Humid air does as well.”
In their prospective study, Dr. Silverberg and colleagues found that 90% of those who had at least three itch triggers reported 3 months or less of AD remission in the past year, “meaning that 90% are reporting persistent disease when they have multiple itch triggers,” he said. In addition, 78% reported two or more flares per year and 61% reported that AD is worse during certain seasons.
Potential mitigation strategies for stress include stress management, biofeedback, meditation, relaxation training, and mindfulness. “These don’t necessarily require expensive psychotherapy,” he said. Freely available iPhone apps can be incorporated into daily practice, such as Calm, Relax with Andrew Johnson, Nature Sounds Relax and Sleep, Breathe2Relax, and Headspace.
Many AD patients are sedentary and avoid vigorous physical activity owing to heat and sweat as triggers. Simple solutions include exercising in a cooler temperature environment, “not just using fans,” he said. “Take a quick shower right after working out and consider pre- and/or post treatment with topical medication.”
High temperature and sweating can be problematic at bedtime, he continued. Even if the indoor temperature is 70° F, that might jump to 85° F or 90° F under a thick blanket. “That heat can trigger itch and may cause sweating, which can trigger itch,” said Dr. Silverberg, who has AD and is director of patch testing at George Washington University. Potential solutions include using a lighter blanket, lowering the indoor temperature, and wearing breathable pajamas.
Dryness, another common AD trigger, can be secondary to a combination of low outdoor and/or indoor humidity. “Lower outdoor humidity is a particular problem in the wintertime, because cold air doesn’t hold moisture as well,” he said. “That’s why the air feels much dryer in the wintertime. There’s also a problem of indoor heating and cooling. Sometimes central air systems can lower humidity to the point where it’s bone dry.”
In an effort to determine the impact of specific climatic factors on the U.S. prevalence of AD, Dr. Silverberg and colleagues conducted a study using a merged analysis of the 2007 National Survey of Children’s Health from a representative sample of 91,642 children aged 0-17 years and 2006-2007 measurements from the National Climate Data Center and Weather Service. They found that childhood AD prevalence was increased in geographical areas that use more indoor heat and cooling and had lower outdoor humidity. “So, we see that there’s a direct correlate of this dryness issue that is leading to more AD throughout the U.S.,” he said.
Practical solutions to mitigate the effect of dry air on AD include opening windows to allow entry of moist air, “which can be particularly helpful in residences that are overheated,” he said. “I deal with this a lot in patients who live in dormitories. Use humidifiers to add moisture back into the air. Aim for 40%-50% indoor humidity to avoid mold and dust mites. It’s better to use demineralized water to reduce bacterial growth. This can be helpful for aeroallergies. Of note, there are really no well-done studies that have examined the efficacy of humidifiers in AD, but based on our anecdotal experience, this is a good way to go.”
Cold temperatures and trigger intense itch, even in the setting of high humidity. “For me personally, this is one of my most brutal triggers,” Dr. Silverberg said. “When I’m in a place with extremes of cold, I get a rapid onset of itch, a mix of itch and pain, particularly on the dorsal hands. For solutions, you can encourage patients to avoid extremely low temperatures, to bundle up, and to potentially use hand warmers or other heating devices.”
Clothing can be a trigger as well, especially tight-fitting clothes, hot and nonbreathable clothes, and large-diameter wool, which has been shown to induce itching and irritation. Mitigation strategies include wearing loose-fitting, lightweight, nonirritating fabric. “Traditional cotton and silk fabrics have mixed evidence in improving AD but are generally safe,” he said. “Ultra- or superfine merino wool has been shown to be nonpruritic. There is sparse evidence to support chemically treated/coated clothing for AD, but this may be an emerging area.”
Dr. Silverberg pointed out variability of cultural perspectives and preferences for bathing practices, including temperature, duration, frequency, optimal bathing products, and the use of loofahs and other scrubbing products. “This stems from different perceptions of what it means to be clean, and how dry our skin should feel after a shower,” he said. “Many clinicians and patients were taught that regular bathing is harmful in AD. It turns out that’s not true.”
In a recently published systematic review and meta-analysis of 13 studies, he and his colleagues examined efficacy outcomes of different bathing/showering regimens in AD. All 13 studies showed numerically reduced AD severity with any bathing regimen in at least one time point. Numerical decreases over time were observed for body surface area (BSA), Eczema Area and Severity Index (EASI), and/or SCORAD measures for daily and less than daily bathing, with or without application of emollients or topical corticosteroids. In random effects regression models, taking baths more than or less than seven times per week were not associated with significant differences of Cohen’s D scores for EASI, SCORAD, or BSA. “The take-home message here is, let your AD patients bathe,” Dr. Silverberg said. “Bathing is good. It can be channeled to help the eczema, but it has to be done the right way.”
Patients should be counseled to use nonirritating cleansers and shampoos, avoid excessively long baths/showers, avoid excessively hot baths/showers, avoid excessive rubbing or scrubbing of skin, and to apply emollients and/or topical corticosteroids immediately after the bath/shower.
PROMIS Itch-Triggers is a simple and feasible checklist to screen for the most common itch triggers in AD in clinical practice (patients are asked to check off which of the following have caused their itch in the previous 7 days: cold temperature, hot temperature, heat, sweat, tight clothing, fragrances, boredom, talking about itch, stress, weather change, sunlight, humid air, dry air). “It takes less than 1 minute to complete,” he said. “Additional testing with skin patch and/or prick testing may be warranted to identify allergenic triggers.”
Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.
FROM REVOLUTIONIZING AD 2020
Dupilumab curbed itch intensity, frequency in children with severe eczema
.
The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“Severe AD is complex, highly symptomatic, multidimensional condition characterized by an intense pruritus that negatively impacts a patient’s life,” said Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami. Published data from the double-blind, placebo-controlled, 16-week, LIBERTY AD PEDS trial in children aged 6–11 years with severe AD showed that dupilumab significantly improved AD signs, symptoms, and quality of life, with an acceptable safety profile (J Am Acad Dermatol. 2020;21:119-31).
For the current analysis, Dr. Yosipovitch and colleagues evaluated the time to onset, magnitude, and sustainability of the effect of dupilumab on different measures of itch using data from approved Food and Drug Administration doses studied in the LIBERTY AD PEDS trial. A total of 243 children aged 6-11 years were randomized to dupilumab 300 mg every 4 weeks (300 mg q4w, baseline weight of less than 30 kg; 600-mg loading dose), 200 mg every 2 weeks (200 mg q2w, baseline weight 30 kg or greater; 400-mg loading dose), or placebo. All patients received concomitant medium-potency topical corticosteroids.
The mean age of patients was 8.4 years and those in the 300-mg q4w group were about 2 years younger than those in the 200-mg q2w group. On the Peak Pruritus Numerical Rating Scale (NRS), the researchers observed that treatment with dupilumab was associated with a significant improvement from baseline in daily worst itch score through day 22 in the 300-mg q4w group and the 200-mg q2w group, compared with placebo (–29% vs. –30%, respectively; P less than or equal to .001 and P less than or equal to .05). Treatment with dupilumab was also associated with a significant improvement from baseline in weekly average of daily worst itch score through week 16, compared with placebo (–55% vs. –58%; P less than or equal to .001). Similarly, a higher daily proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (51% vs. 49%; P less than or equal to .001 and P less than or equal to .05). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (21% in both groups; P less than or equal to .05).
By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).
Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.
“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.
.
The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“Severe AD is complex, highly symptomatic, multidimensional condition characterized by an intense pruritus that negatively impacts a patient’s life,” said Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami. Published data from the double-blind, placebo-controlled, 16-week, LIBERTY AD PEDS trial in children aged 6–11 years with severe AD showed that dupilumab significantly improved AD signs, symptoms, and quality of life, with an acceptable safety profile (J Am Acad Dermatol. 2020;21:119-31).
For the current analysis, Dr. Yosipovitch and colleagues evaluated the time to onset, magnitude, and sustainability of the effect of dupilumab on different measures of itch using data from approved Food and Drug Administration doses studied in the LIBERTY AD PEDS trial. A total of 243 children aged 6-11 years were randomized to dupilumab 300 mg every 4 weeks (300 mg q4w, baseline weight of less than 30 kg; 600-mg loading dose), 200 mg every 2 weeks (200 mg q2w, baseline weight 30 kg or greater; 400-mg loading dose), or placebo. All patients received concomitant medium-potency topical corticosteroids.
The mean age of patients was 8.4 years and those in the 300-mg q4w group were about 2 years younger than those in the 200-mg q2w group. On the Peak Pruritus Numerical Rating Scale (NRS), the researchers observed that treatment with dupilumab was associated with a significant improvement from baseline in daily worst itch score through day 22 in the 300-mg q4w group and the 200-mg q2w group, compared with placebo (–29% vs. –30%, respectively; P less than or equal to .001 and P less than or equal to .05). Treatment with dupilumab was also associated with a significant improvement from baseline in weekly average of daily worst itch score through week 16, compared with placebo (–55% vs. –58%; P less than or equal to .001). Similarly, a higher daily proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (51% vs. 49%; P less than or equal to .001 and P less than or equal to .05). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (21% in both groups; P less than or equal to .05).
By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).
Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.
“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.
.
The findings come from a post hoc analysis of a phase 3 trial known as LIBERTY AD PEDS (NCT03345914) that Gil Yosipovitch, MD, presented during a late-breaking research session at the Revolutionizing Atopic Dermatitis virtual symposium.
“Severe AD is complex, highly symptomatic, multidimensional condition characterized by an intense pruritus that negatively impacts a patient’s life,” said Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami. Published data from the double-blind, placebo-controlled, 16-week, LIBERTY AD PEDS trial in children aged 6–11 years with severe AD showed that dupilumab significantly improved AD signs, symptoms, and quality of life, with an acceptable safety profile (J Am Acad Dermatol. 2020;21:119-31).
For the current analysis, Dr. Yosipovitch and colleagues evaluated the time to onset, magnitude, and sustainability of the effect of dupilumab on different measures of itch using data from approved Food and Drug Administration doses studied in the LIBERTY AD PEDS trial. A total of 243 children aged 6-11 years were randomized to dupilumab 300 mg every 4 weeks (300 mg q4w, baseline weight of less than 30 kg; 600-mg loading dose), 200 mg every 2 weeks (200 mg q2w, baseline weight 30 kg or greater; 400-mg loading dose), or placebo. All patients received concomitant medium-potency topical corticosteroids.
The mean age of patients was 8.4 years and those in the 300-mg q4w group were about 2 years younger than those in the 200-mg q2w group. On the Peak Pruritus Numerical Rating Scale (NRS), the researchers observed that treatment with dupilumab was associated with a significant improvement from baseline in daily worst itch score through day 22 in the 300-mg q4w group and the 200-mg q2w group, compared with placebo (–29% vs. –30%, respectively; P less than or equal to .001 and P less than or equal to .05). Treatment with dupilumab was also associated with a significant improvement from baseline in weekly average of daily worst itch score through week 16, compared with placebo (–55% vs. –58%; P less than or equal to .001). Similarly, a higher daily proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (51% vs. 49%; P less than or equal to .001 and P less than or equal to .05). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (21% in both groups; P less than or equal to .05).
By week 16, a higher weekly proportion of dupilumab-treated patients achieved a 2-point or more improvement in worst itch score, compared with placebo (72% in the 300-mg q4w group vs. 74% in the 200-mg q2w group; P less than or equal to .001). The same association held true for the daily proportion of dupilumab-treated patients who achieved a 4-point or more improvement in worst itch score, compared with placebo (54% vs. 61%; P less than or equal to .001).
Next, the researchers evaluated the proportion of patients reporting the number of days with itchy skin over the previous 7 days as assessed from the Patient-Oriented Eczema Measure (POEM) itch item question: “Over the last week, on how many days has your child’s skin been itchy because of their eczema?” By week 16, the majority of children treated with dupilumab achieved a reduction of days experiencing itch from every day at baseline to at most 2 days, with some improvement to zero days per week.
“Overall, in the LIBERTY AD PEDS trial, dupilumab was well tolerated and data were consistent with the known dupilumab safety profile observed in adults and adolescents,” Dr. Yosipovitch said. “Injection site reactions and conjunctivitis were more common with dupilumab. Infections and AD exacerbations were more common with placebo.”
The study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Yosipovitch and coauthors reporting having received financial grants and research grants from numerous pharmaceutical companies.
REPORTING FROM REVOLUTIONIZING AD 2020