Atopic Dermatitis

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

It is unsurprising that food frequently is thought to be the culprit behind an eczema flare, especially in infants. Indeed, it often is said that infants do only 3 things: eat, sleep, and poop.¹ For those unfortunate enough to develop the signs and symptoms of atopic dermatitis (AD), food quickly emerges as a potential culprit from the tiny pool of suspects, which is against a cultural backdrop of unprecedented focus on foods and food reactions.² The prevalence of food allergies in children, though admittedly fraught with methodological difficulties, is estimated to have more than doubled from 3.4% in 1999 to 7.6% in 2018.³ As expected, prevalence rates were higher among children with other atopic comorbidities including AD, with up to 50% of children with AD demonstrating convincing food allergy.⁴ It is easy to imagine a patient conflating these 2 entities and mistaking their correlation for causation. Thus, it follows that more than 90% of parents/guardians have reported that their children have had food-induced AD, and understandably—at least according to one study—75% of parents/guardians were found to have manipulated the diet in an attempt to manage the disease.^5,6

Patients and parents/guardians are not the only ones who have suspected food as a driving force in AD. An article in the British Medical Journal from the 1800s beautifully encapsulated the depth and duration of this quandary: “There is probably no subject in which more deeply rooted convictions have been held, not only in the profession but by the laity, than the connection between diet and disease, both as regards the causation and treatment of the latter.”⁷ Herein, a wide range of food reactions is examined to highlight evidence for the role of diet in AD, which may contradict what patients—and even some clinicians—believe.

No Easy Answers

A definitive statement that food allergy is not the root cause of AD would put this issue to rest, but such simplicity does not reflect the complex reality. First, we must agree on definitions for certain terms. What do we mean by food allergy? A broader category—adverse food reactions—covers a wide range of entities, some immune mediated and some not, including lactose intolerance, irritant contact dermatitis around the mouth, and even dermatitis herpetiformis (the cutaneous manifestation of celiac disease).⁸ Although the term food allergy often is used synonymously with adverse food reactions, the exact definition of a food allergy is specific: “adverse immune responses to food proteins that result in typical clinical symptoms.”⁸ The fact that many patients and even health care practitioners seem to frequently misapply this term makes it even more confusing. 

The current focus is on foods that could trigger a flare of AD, which clearly is a broader question than food allergy sensu stricto. It seems self-evident, for example, that if an infant with AD were to (messily) eat an acidic food such as an orange, a flare-up of AD around the mouth and on the cheeks and hands would be a forgone conclusion. Similar nonimmunologic scenarios unambiguously can occur with many foods, including citrus; corn; radish; mustard; garlic; onion; pineapple; and many spices, food additives, and preservatives.⁹ Clearly there are some scenarios whereby food could trigger an AD flare, and yet this more limited vignette generally is not what patients are referring to when suggesting that food is the root cause of their AD.

The Labyrinth of Testing for Food Allergies

Although there is no reliable method for testing for irritant dermatitis, understanding the other types of tests may help guide our thinking. Testing for IgE-mediated food allergies generally is done via an immunoenzymatic serum assay that can document sensitization to a food protein; however, this testing by itself is not sufficient to diagnose a clinical food allergy.¹⁰ Similarly, skin prick testing allows for intradermal administration of a food extract to evaluate for an urticarial reaction within 10 to 15 minutes. Although the sensitivity and specificity vary by age, population, and the specific allergen being tested, these are limited to immediate-type reactions and do not reflect the potential to drive an eczematous flare.

The gold standard, if there is one, is likely the double-blind, placebo-controlled food challenge (DBPCFC), ideally with a long enough observation period to capture later-occurring reactions such as an AD flare. However, given the nature of the test—having patients eat the foods of concern and then carefully following them for reactions—it remains time consuming, expensive, and labor intensive.¹¹ 

To further complicate matters, several unvalidated tests exist such as IgG testing, atopy patch testing, kinesiology, and hair and gastric juice analysis, which remain investigational but continue to be used and may further confuse patients and clinicians.¹²

It is useful to first separate out the classic IgE-mediated food allergy reactions that are common. In these immediate-type reactions, a person sensitized to a food protein will develop characteristic cutaneous and/or extracutaneous reactions such as urticaria, angioedema, and even anaphylaxis, usually within minutes of exposure. Although it is possible that an IgE-mediated reaction could trigger an AD flare—perhaps simply by causing pruritus, which could initiate the itch-scratch cycle—because of the near simultaneity with ingestion of the offending food and the often dramatic clinical presentations, such foods clearly do not represent “hidden” triggers for AD flares.³ The concept of food-triggered AD (FTAD) is crucial for thinking about foods that could result in true eczematous flares, which historically have been classified as early-type (<2 hours after food challenge) and late-type (≥2 hours after food challenge) reactions.^13,14 

A study of more than 1000 DBPCFCs performed in patients with AD was illustrative.¹⁵ Immediate reactions other than AD were fairly common and were observed in 40% of the food challenges compared to only 9% in the placebo group. These reactions included urticaria, angioedema, and gastrointestinal and respiratory tract symptoms. Immediate reactions of AD alone were exceedingly rare at only 0.7% and not significantly elevated compared to placebo. Just over 4% experienced both an immediate AD exacerbation along with other non-AD findings, which was significantly greater than placebo (P<.01). Although intermediate and late reactions manifesting as AD exacerbations did occur after food ingestion, they were rare (2.2% or less) and not significantly different from placebo. The authors concluded that an exacerbation of AD in the absence of other allergic symptoms in children was unlikely to be due to food,¹⁵ which is an important finding.

A recent retrospective review of 372 children with AD reported similar results.⁴ The authors defined FTAD in a different way; instead of showing a flare after a DBPCFC, they looked for “physician-noted sustained improvement in AD upon removal of a food (typically after 2–6-wk follow-up), to which the child was sensitized without any other changes in skin care.” Despite this fundamentally different approach, they similarly concluded that while food allergies were common, FTAD was relatively uncommon—found in 2% of those with mild AD, 6% of those with moderate AD, and 4% of those with severe AD.⁴ 

There are other ways that foods could contribute to disease flares, however, and one of the most compelling is that there may be broader concepts at play; perhaps some diets are not specifically driving the AD but rather are affecting inflammation in the body at large. Although somewhat speculative, there is evidence that some foods may simply be proinflammatory, working to exacerbate the disease outside of a specific mechanism, which has been seen in a variety of other conditions such as acne or rheumatoid arthritis.^16,17 To speculate further, it is possible that there may be a threshold effect such that when the AD is poorly controlled, certain factors such as inflammatory foods could lead to a flare, while when under better control, these same factors may not cause an effect.

Finally, it is important to also consider the emotional and/or psychological aspects related to food and diet. The power of the placebo in dietary change has been documented in several diseases, though this certainly is not to be dismissive of the patient’s symptoms; it seems reasonable that the very act of changing such a fundamental aspect of daily life could result in a placebo effect.^18,19 In the context of relapsing and remitting conditions such as AD, this effect may be magnified. A landmark study by Thompson and Hanifin²⁰ illustrates this possibility. The authors found that in 80% of cases in which patients were convinced that food was a major contributing factor to their AD, such concerns diminished markedly once better control of the eczema was achieved.²⁰

This brings us to what to do with an individual patient in the examination room. Because there is such widespread concern and discussion around this topic, it is important to at least briefly address it. If there are known food allergens that are being avoided, it is important to underscore the importance of continuing to avoid those foods, especially when there is actual evidence of true food allergy rather than sensitization alone. Historically, elimination diets often were recommended empirically, though more recent studies, meta-analyses, and guidance documents increasingly have recommended against them.³ In particular, there are major concerns for iatrogenic harm. 

First, heavily restricted diets may result in nutritional and/or caloric deficiencies that can be dangerous and lead to poor growth.²¹ Practices such as drinking unpasteurized milk can expose children to dangerous infections, while feeding them exclusively rice milk can lead to severe malnutrition.²² 

Second, there is a dawning realization that children with AD placed on elimination diets may actually develop true IgE-mediated allergies, including fatal anaphylaxis, to the excluded foods. In fact, one retrospective review of 298 patients with a history of AD and no prior immediate reactions found that 19% of patients developed new immediate-type hypersensitivity reactions after starting an elimination diet, presumably due to the loss of tolerance to these foods. A striking one-third of these reactions were classified as anaphylaxis, with cow’s milk and egg being the most common offenders.²³

It also is crucial to acknowledge that recommending sweeping lifestyle changes is not easy for patients, especially pediatric patients. Onerous dietary restrictions may add considerable stress, ironically a known trigger for AD itself. 

Finally, dietary modifications can be a distraction from conventional therapy and may result in treatment delays while the patient continues to experience uncontrolled symptoms of AD. 

Final Thoughts

Diet is intimately related to AD. Although the narrative continues to unfold in fascinating domains, such as the skin barrier and the microbiome, it is increasingly clear that these are intertwined and always have been. Despite the rarity of true food-triggered AD, the perception of dietary triggers is so widespread and addressing the topic is important and may help avoid unnecessary harm from unfounded extreme dietary changes. A recent multispecialty workgroup report on AD and food allergy succinctly summarized this as: “AD has many triggers and comorbidities, and food allergy is only one of the potential triggers and comorbid conditions. With regard to AD management, education and skin care are most important.”³ With proper testing, guidance, and both topical and systemic therapies, most AD can be brought under control, and for at least some patients, this may allay concerns about foods triggering their AD. 

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

Atopic dermatitis (AD), or eczema, is a common inflammatory skin disease notorious for its chronic, relapsing, and often frustrating disease course. Although as many as 25% of children in the United States are affected by this condition and its impact on the quality of life of affected patients and families is profound,^1-3 therapeutic advances in the pediatric population have been fairly limited until recently.

Over the last 10 years, there has been robust investigation into pediatric AD therapeutics, with many topical and systemic medications either recently approved or under clinical investigation. These developments are changing the landscape of the management of pediatric AD and raise a set of fascinating questions about how early and aggressive intervention might change the course of this disease. We discuss current limitations in the field that may be addressed with additional research.

New Topical Medications

In the last several years, there has been a rapid increase in efforts to develop new topical agents to manage AD. Until the beginning of the 21st century, the dermatologist’s arsenal was limited to topical corticosteroids (TCs). In the early 2000s, attention shifted to topical calcineurin inhibitors as nonsteroidal alternatives when the US Food and Drug Administration (FDA) approved topical tacrolimus and pimecrolimus for AD. In 2016, crisaborole (a phosphodiesterase-4 [PDE4] inhibitor) was approved by the FDA for use in mild to moderate AD in patients 2 years and older, marking a new age of development for topical AD therapies. In 2021, the FDA approved ruxolitinib (a topical Janus kinase [JAK] 1/2 inhibitor) for use in mild to moderate AD in patients 12 years and older.

Roflumilast (ARQ-151) and difamilast (OPA-15406)(members of the PDE4 inhibitor class) are undergoing investigation for pediatric AD. A phase 3 clinical trial for roflumilast for AD is underway (ClinicalTrial.gov Identifier: NCT04845620); it is already approved for psoriasis in patients 12 years and older. A phase 3 trial of difamilast (NCT03911401) was recently completed, with results supporting the drug’s safety and efficacy in AD management.⁴ Efforts to synthesize new better-targeted PDE4 inhibitors are ongoing.⁵

Tapinarof (a novel aryl hydrocarbon receptor-modulating agent) is approved for psoriasis in adults, and a phase 3 trial for management of pediatric AD is underway (NCT05032859) after phase 2 trials revealed promising results.⁶

Lastly, the microbiome is a target for AD topical therapies. A recently completed phase 1 trial of bacteriotherapy with Staphylococcus hominis A9 transplant lotion showed promising results (NCT03151148).⁷ Although this bacteriotherapy technique is early in development and has been studied only in adult patients, results are exciting because they represent a gateway to a largely unexplored realm of potential future therapies.

Standard of Care—How will these new topical therapies impact our standard of care for pediatric AD patients? Topical corticosteroids are still a pillar of topical AD therapy, but the potential for nonsteroidal topical agents as alternatives and used in combination therapeutic regimens has expanded exponentially. It is uncertain how we might individualize regimens tailored to patient-specific factors because the standard approach has been to test drugs as monotherapy, with vehicle comparisons or with reference medications in Europe.

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹

The study of these and other advanced systemic therapies for eczematous dermatitis is transforming the toolbox for pediatric AD care. Although long-term data are lacking for some of these medications, it is possible that newer agents may decrease reliance on older immunosuppressants, such as systemic corticosteroids, cyclosporine, and methotrexate. Unanswered questions include: How and which systemic medications may alter the course of the disease? What is the disease modification for AD? What is the impact on comorbidities over time?

What’s Missing?

The field of pediatric AD has experienced exciting new developments with the emergence of targeted therapeutics, but those new agents require more long-term study, though we already have longer-term data on crisaborole and dupilumab.^10-14,20 Studies of the long-term use of these new treatments on comorbidities of pediatric AD—mental health outcomes, cardiovascular disease, effects on the family, and other allergic conditions—are needed.²¹ Furthermore, clinical guidelines that address indications, timing of use, tapering, and discontinuation of new treatments depend on long-term experience and data collection.

Therefore, it is prudent that investigators, companies, payers, patients, and families support phase 4, long-term extension, and registry studies, which will expand our knowledge of AD medications and their impact on the disease over time.

Final Thoughts

Medications to treat AD are reaching a new level of advancement—from topical agents that target novel pathways to revolutionary biologics and systemic medications. Although there are knowledge gaps on these new therapeutics, the standard of care is already rapidly changing as the expectations of clinicians, patients, and families advance with each addition to the provider’s toolbox.

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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

MONTREAL – Children and young people with severe atopic dermatitis had a more rapid treatment response with ciclosporin, but more sustained disease control with methotrexate in the TREAT study, investigators reported at the annual meeting of the International Society of Atopic Dermatitis.

The findings are important, since many regulatory bodies require patients to have tried such first-line conventional systemic therapies before moving on to novel therapeutics, explained Carsten Flohr, MD, PhD, research and development lead at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust London.

“We don’t really have much pediatric trial data; very often the pediatric data that we have is buried in adult trials and when it comes to an adequately powered randomized controlled trial with conventional systemic medication in pediatric patients, we don’t have one – so we’re lacking that gold standard,” said Dr. Flohr, chair in dermatology and population health sciences at King’s College London.

In the TREAT trial, 103 patients with AD (mean age, 10 years) who had not responded to topical treatment, were randomly assigned to oral ciclosporin (4 mg/kg daily) or methotrexate (0.4 mg/kg weekly) for 36 weeks and then followed for another 24 weeks off therapy for the co-primary outcomes of change in objective Scoring Atopic Dermatitis (o-SCORAD) at 12 weeks, as well as time to first significant flare after treatment cessation, defined as returning to baseline o-SCORAD, or restarting a systemic treatment.

Secondary outcomes included disease severity and quality of life (QOL) measures, as well as safety. At baseline, the mean o-SCORAD was 46.81, with mean Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM) scores of 28.05 and 20.62 respectively. The mean Children’s Dermatology Life Quality Index (CDLQI) score was 14.96.

Looking at change in eczema severity measured by o-SCORAD at 12 weeks, ciclosporin was superior to methotrexate, with a mean difference in o-SCORAD change of -5.69 (P =.01). For the co-primary endpoint of time to first significant flare during the 24 weeks after treatment cessation, “there was a trend toward more flare activity in the ciclosporin group, although with a hazard ratio of 1.55, this was statistically not significant,” Dr. Flohr said.

On a graph showing mean EASI scores from baseline through the 60-week study period, Dr. Flohr explained how the score first dropped more precipitously in patients treated with ciclosporin compared with those treated with methotrexate, reaching a statistically significant difference between the groups by 12 weeks (–3.13, P = .0145).

However, after that time, while the EASI score among those on methotrexate continued to drop, the ciclosporin score evened out, so that by 20 weeks, methotrexate EASI scores were better, and remained so until the end of treatment and further, out to 60 weeks (mean difference -6.36, P < .001). “The most interesting bit of this graph is [that] the curve is pointing downwards for methotrexate up to the 9-month point, suggesting these people had not reached their full therapeutic potential yet, whereas if you’re on ciclosporin you plateau and there’s not much additional improvement, if at all, and then people [on ciclosporin] start going up in their disease activity off therapy,” he said.

The same pattern was seen with all the other outcome measures, including o-SCORAD and POEM.

Quality of life significantly improved by about 8 points in both treatment groups, with no significant differences between groups, and this improvement was sustained through the 24 weeks following cessation of therapy. However, during this treatment-free phase, patients on methotrexate had fewer parent-reported flares compared with those on ciclosporin (mean 6.19 vs 5.40 flares, P =.0251), although there was no difference between groups in time to first flare.

Describing the treatment safety as “overall reassuring,” Dr. Flohr said there were slightly more nonserious adverse events in the methotrexate arm (407 vs. 369), with nausea occurring more often in this group (43.1% vs. 17.6%).

“I think we were seeing this clinically, but to see it in a clinical trial gives us more confidence in discussing with parents,” said session moderator Melinda Gooderham, MD, assistant professor at Queens University, Kingston, Ont., and medical director at the SKiN Centre for Dermatology in Peterborough.

What she also took away from the study was safety of these treatments. “The discontinuation rate was not different with either drug, so it’s not like ciclosporin works fast but all these people have problems and discontinue,” Dr. Gooderham told this news organization. “That’s also reassuring.”

Asked which treatment she prefers, Dr. Gooderham, a consultant physician at Peterborough Regional Health Centre, picked methotrexate “because of the lasting effect. But there are times when you may need more rapid control ... where I might choose ciclosporin first, but for me it’s maybe 90% methotrexate first, 10% ciclosporin.”

Dr. Flohr and Dr. Gooderham report no relevant financial relationships. The study was funded by the National Institute for Health and Care Research.

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

MONTREAL – An online behavioral intervention called Eczema Care Online, aimed at supporting self-management of atopic dermatitis (AD), resulted in a “small but sustained” improvement in eczema severity for up to 1 year, according to two randomized controlled trials presented at the annual meeting of the International Society of Atopic Dermatitis.

The intervention, directed either at parents of children with AD or young adults with AD, “is very low cost, evidence based, easily accessible, and free from possible commercial bias,” said investigator Kim Thomas, MD, professor of applied dermatology research and codirector of the Centre of Evidence Based Dermatology, faculty of medicine & health sciences, University of Nottingham (England).

The main focus of the intervention, along with general education, is “getting control” of the condition with flare-control creams and “keeping control” with regular emollient use.

Efficacy of the intervention, available free online, was compared with “usual eczema care” in 340 parents of children with AD up to age 12 and 337 young patients with AD aged 13-25. Participants were randomized to the intervention plus usual care or usual care alone. The primary outcome was the Patient-Oriented Eczema Measure(POEM) at 24 weeks, with a further measurement at 52 weeks.

In the parent group, about half were women and 83% were White, and the median age of their children was 4 years. About 50% of parents had a university degree, making them “possibly better educated than we might want our target audience for this type of intervention,” Dr. Thomas commented. Most of the children had moderate AD.

In the young patient group, the mean age was 19 years, more than three-quarters were female, 83% were White, and most had moderate AD.

At 24 weeks, both intervention groups had improved POEM scores, compared with controls, with a mean difference of 1.5 points in the parent group (P = .002) and 1.7 points in the young patient group (P = .04). “A small difference, but statistically significant and sustained,” Dr. Thomas said, adding that this difference was sustained up to 52 weeks.

In terms of mechanism of action, a secondary outcome looked at the concept of enablement, “which again, seemed to be improved in the intervention group, which suggests it’s something to do with being able to understand and cope with their disease better,” she said. The tool is targeted to “people who wouldn’t normally get to a dermatologist and certainly wouldn’t get access to group interventions.”

An additional aim of the intervention was “to provide a single, consistent message received from every point of contact that people might engage with ... [from] community doctors, pharmacists, dermatologists, and importantly, eczema charities all signposting [the intervention] and sharing a consistent message.”

While the intervention is free and available to patients anywhere, Dr. Thomas emphasized that it is tailored to the U.K. health care system. “If people would like to get in touch and help work with us to maybe adapt it slightly to make it more suitable for your own health care systems, that’s something we’d be very happy to look at with you.”

Asked for comment, Natalie Cunningham, MD, panel moderator, was lukewarm about the tool. “It can be a supplement, but you can never replace the one-on-one patient–health care provider interaction,” she told this news organization. “That could be provided by a nondermatologist and supplemented by an online component,” said Dr. Cunningham, from the Izaak Walton Killam Hospital for Children in Halifax, N.S.

“First-line treatment for eczema, no matter what kind of eczema, is topical steroids, and that is something that requires a lot of education – and something you want to do one on one in person because everyone comes to it with a different experience, baggage, or understanding,” she said. “We need to figure out what the barrier is so that you can do the right education.”

In addition, with systemic AD therapies currently approved for children, parents and young patients need to be able to advocate for specialist care to access these medications, she noted.

Dr. Thomas and Dr. Cunningham reported no relevant financial relationships.

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

MONTREAL – An online behavioral intervention called Eczema Care Online, aimed at supporting self-management of atopic dermatitis (AD), resulted in a “small but sustained” improvement in eczema severity for up to 1 year, according to two randomized controlled trials presented at the annual meeting of the International Society of Atopic Dermatitis.

The intervention, directed either at parents of children with AD or young adults with AD, “is very low cost, evidence based, easily accessible, and free from possible commercial bias,” said investigator Kim Thomas, MD, professor of applied dermatology research and codirector of the Centre of Evidence Based Dermatology, faculty of medicine & health sciences, University of Nottingham (England).

The main focus of the intervention, along with general education, is “getting control” of the condition with flare-control creams and “keeping control” with regular emollient use.

Efficacy of the intervention, available free online, was compared with “usual eczema care” in 340 parents of children with AD up to age 12 and 337 young patients with AD aged 13-25. Participants were randomized to the intervention plus usual care or usual care alone. The primary outcome was the Patient-Oriented Eczema Measure(POEM) at 24 weeks, with a further measurement at 52 weeks.

In the parent group, about half were women and 83% were White, and the median age of their children was 4 years. About 50% of parents had a university degree, making them “possibly better educated than we might want our target audience for this type of intervention,” Dr. Thomas commented. Most of the children had moderate AD.

In the young patient group, the mean age was 19 years, more than three-quarters were female, 83% were White, and most had moderate AD.

At 24 weeks, both intervention groups had improved POEM scores, compared with controls, with a mean difference of 1.5 points in the parent group (P = .002) and 1.7 points in the young patient group (P = .04). “A small difference, but statistically significant and sustained,” Dr. Thomas said, adding that this difference was sustained up to 52 weeks.

In terms of mechanism of action, a secondary outcome looked at the concept of enablement, “which again, seemed to be improved in the intervention group, which suggests it’s something to do with being able to understand and cope with their disease better,” she said. The tool is targeted to “people who wouldn’t normally get to a dermatologist and certainly wouldn’t get access to group interventions.”

An additional aim of the intervention was “to provide a single, consistent message received from every point of contact that people might engage with ... [from] community doctors, pharmacists, dermatologists, and importantly, eczema charities all signposting [the intervention] and sharing a consistent message.”

While the intervention is free and available to patients anywhere, Dr. Thomas emphasized that it is tailored to the U.K. health care system. “If people would like to get in touch and help work with us to maybe adapt it slightly to make it more suitable for your own health care systems, that’s something we’d be very happy to look at with you.”

Asked for comment, Natalie Cunningham, MD, panel moderator, was lukewarm about the tool. “It can be a supplement, but you can never replace the one-on-one patient–health care provider interaction,” she told this news organization. “That could be provided by a nondermatologist and supplemented by an online component,” said Dr. Cunningham, from the Izaak Walton Killam Hospital for Children in Halifax, N.S.

“First-line treatment for eczema, no matter what kind of eczema, is topical steroids, and that is something that requires a lot of education – and something you want to do one on one in person because everyone comes to it with a different experience, baggage, or understanding,” she said. “We need to figure out what the barrier is so that you can do the right education.”

In addition, with systemic AD therapies currently approved for children, parents and young patients need to be able to advocate for specialist care to access these medications, she noted.

Dr. Thomas and Dr. Cunningham reported no relevant financial relationships.

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

MONTREAL – An online behavioral intervention called Eczema Care Online, aimed at supporting self-management of atopic dermatitis (AD), resulted in a “small but sustained” improvement in eczema severity for up to 1 year, according to two randomized controlled trials presented at the annual meeting of the International Society of Atopic Dermatitis.

The intervention, directed either at parents of children with AD or young adults with AD, “is very low cost, evidence based, easily accessible, and free from possible commercial bias,” said investigator Kim Thomas, MD, professor of applied dermatology research and codirector of the Centre of Evidence Based Dermatology, faculty of medicine & health sciences, University of Nottingham (England).

The main focus of the intervention, along with general education, is “getting control” of the condition with flare-control creams and “keeping control” with regular emollient use.

Efficacy of the intervention, available free online, was compared with “usual eczema care” in 340 parents of children with AD up to age 12 and 337 young patients with AD aged 13-25. Participants were randomized to the intervention plus usual care or usual care alone. The primary outcome was the Patient-Oriented Eczema Measure(POEM) at 24 weeks, with a further measurement at 52 weeks.

In the parent group, about half were women and 83% were White, and the median age of their children was 4 years. About 50% of parents had a university degree, making them “possibly better educated than we might want our target audience for this type of intervention,” Dr. Thomas commented. Most of the children had moderate AD.

In the young patient group, the mean age was 19 years, more than three-quarters were female, 83% were White, and most had moderate AD.

At 24 weeks, both intervention groups had improved POEM scores, compared with controls, with a mean difference of 1.5 points in the parent group (P = .002) and 1.7 points in the young patient group (P = .04). “A small difference, but statistically significant and sustained,” Dr. Thomas said, adding that this difference was sustained up to 52 weeks.

In terms of mechanism of action, a secondary outcome looked at the concept of enablement, “which again, seemed to be improved in the intervention group, which suggests it’s something to do with being able to understand and cope with their disease better,” she said. The tool is targeted to “people who wouldn’t normally get to a dermatologist and certainly wouldn’t get access to group interventions.”

An additional aim of the intervention was “to provide a single, consistent message received from every point of contact that people might engage with ... [from] community doctors, pharmacists, dermatologists, and importantly, eczema charities all signposting [the intervention] and sharing a consistent message.”

While the intervention is free and available to patients anywhere, Dr. Thomas emphasized that it is tailored to the U.K. health care system. “If people would like to get in touch and help work with us to maybe adapt it slightly to make it more suitable for your own health care systems, that’s something we’d be very happy to look at with you.”

Asked for comment, Natalie Cunningham, MD, panel moderator, was lukewarm about the tool. “It can be a supplement, but you can never replace the one-on-one patient–health care provider interaction,” she told this news organization. “That could be provided by a nondermatologist and supplemented by an online component,” said Dr. Cunningham, from the Izaak Walton Killam Hospital for Children in Halifax, N.S.

“First-line treatment for eczema, no matter what kind of eczema, is topical steroids, and that is something that requires a lot of education – and something you want to do one on one in person because everyone comes to it with a different experience, baggage, or understanding,” she said. “We need to figure out what the barrier is so that you can do the right education.”

In addition, with systemic AD therapies currently approved for children, parents and young patients need to be able to advocate for specialist care to access these medications, she noted.

Dr. Thomas and Dr. Cunningham reported no relevant financial relationships.

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

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

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Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

PicturePartners/Getty Images

Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Peter A. Lio, MD, is a big user of the “big guns” for his patients with atopic dermatitis – biologics, conventional immunosuppressants, and JAK inhibitors. But he also has a big menu of treatments – from oral hempseed oil and black tea compresses to probiotics and acupressure – that he encourages patients to try as they use the big guns, or as they attempt to wean off of them or avoid their use altogether.

During a presentation at the annual Integrative Dermatology Symposium, Dr. Lio said that he uses “5 pillars” to guide his integrative treatment plans: The skin barrier, the psyche, the microbiome, inflammation, and itch. “I try to flag approaches that predominantly address the categories that I think need the most help,” he said. “And I tell patients [which pillar or pillars] each treatment is addressing.”

PicturePartners/Getty Images

Most commonly, the greatest challenge with AD – and the “single biggest weakness of conventional Western medicine” – lies not with getting patients clear in the first place, but in keeping them clear safely, he said. “I don’t think that using immunosuppressive [medications] is okay for the long-term unless there is no other choice,” said Dr. Lio, who cofounded the Chicago Integrative Eczema Center about 6 years ago and is clinical assistant professor of dermatology and pediatrics at Northwestern University, Chicago. Oftentimes, he said, complementary approaches, including dietary changes, can also serve as supportive adjunctive therapy to biologics and JAK inhibitors.

He has three main criteria, or “filters,” for evaluating these treatments before recommending them to patients: At least some clinical evidence for efficacy (preferably randomized trials but not necessarily), safety, and practicality. The “only way we’re going to move things forward [for AD and other conditions] is to try out less tested treatments ... to open up to them,” Dr. Lio said in an interview after the meeting. And in doing so, he said, dermatologists “can connect with a lot of patients whom naysayers can’t connect with.”
 

An integrative menu

Dr. Lio individualizes plans, suggesting treatments after “listening to patients’ stories” and considering their age, history, symptoms and skin presentation, and other factors. He said he “goes little by little,” telling a patient, for instance, “I’d love for us to try adding a little hemp oil to your diet.”

If patients aren’t pleased with or are tired of treatments, he said in the interview, “we move on and try something else.”

At the meeting, he described some of the treatments on his menu and the supporting evidence for those treatments:

Oral hempseed oil. A randomized crossover study of 20 adult patients with AD found that daily consumption of 2 tablespoons of hempseed oil decreased skin dryness, itchiness, and use of topical medications compared with consumption of olive oil. “It was statistically significant and seemed clinically meaningful,” likely resulting from the high concentration of polyunsaturated fatty acids in the oil, Dr. Lio said.

Topical vitamin B12. In a phase 3 randomized controlled trial of topical B₁₂ applied twice a day for 8 weeks, patients experienced significant improvements in the extent and severity of AD compared with placebo. Another study in children with AD aged 6 months to 18 years found significant improvement in as early as 2 weeks of use. “It really does help, and is very gentle in babies,” Dr. Lio said.

Black tea compresses. “It’s absolutely my favorite kind of compress,” he said. “It was studied on the face and eyelids but I use it all over the body for adults and kids.” A German study of 22 patients with AD or contact facial dermatitis showed significant improvements in facial dermatitis within the first 3 days of treatment with application of black tea dressings plus an emollient cream, with significant reductions in four disease activity scores (the Facial Eczema Area and Severity Index, visual analog scale for pruritus, Investigator’s Global Assessment score, and Patient’s Self-Assessment Score) that continued through day 6.

Oolong tea. In a 2001 study, after 1 month of drinking oolong tea after each meal, 64% of patients with recalcitrant AD who continued with their regular treatment showed marked to moderate improvements in AD, with a beneficial effect first noticed after 1-2 weeks. At 6 months, 54% still had a good response to treatment. “It’s super cheap and accessible,” Dr. Lio said.

Coconut oil. One of the greatest benefits of coconut oil is on the microbiome and the dysbiosis that can result from a disrupted, or “leaky,” skin barrier – especially overgrowth of Staphylococcus aureus, which “drives AD,” Dr. Lio said. In a study of adults with AD from the Philippines, topically applied coconut oil decreased S. aureus colonization by 95% when applied twice daily for 4 weeks, compared with a 50% decrease in an olive oil control group. Other research has shown coconut oil to be superior to mineral oil as a moisturizer, he said at the meeting.

Acupressure. After a pilot study conducted by Dr. Lio and colleagues showed greater decreases in itch (per the visual analogue scale) in adults with AD who applied an acupressure bead at the LI11 point (near the elbow) for 3 minutes three times a week for 4 weeks, than among those who did not use the acupressure tool, Dr. Lio began trying it with some of his patients. “Now I use it broadly,” he added in the interview. “Kids over 10 can figure out how to use it and teenagers love it [to relief itch]. Some don’t use the beads anymore, they just use their fingertips.”
 

Advice on diet, vitamin D, and probiotics

AD severity is “powerfully” correlated with IgE food allergy, but Dr. Lio said at the meeting that he currently takes a cautious approach toward strict elimination diets.

There is a growing school of thought among allergists, he said, that positive IgE tests without evidence of acute reactions may not indicate true allergy, but rather sensitivity – and may not warrant food eliminations. And as has been shown with peanuts, there can be a serious downside to elimination, as food avoidance can lead to serious allergy later on, he said.

“More and more people are thinking that if you can tolerate [a food], continue it,” he added in the interview. In the absence of clear reactions, the only way to really know if a food is making eczema worse is to do a double-blind, placebo-controlled food challenge test, he noted.

Patients often come to see him believing that food is the “root cause” of their eczema and feeling frustrated, even anxious, about strict dietary restrictions they’ve implemented. But for many of these patients, the right question “would be to ask, why is my eczema causing my food allergy?” he said at the meeting, referring to the epithelial barrier hypothesis, which posits that skin barrier dysfunction can lead to asthma, allergic rhinitis, and food allergy.

Dr. Lio often recommends the Autoimmune Protocol (AIP) diet, a “close cousin” of the paleo diet for patients with AD, as general guidance to be followed “holistically” and often without the strict eliminations it prescribes. Minimizing processed foods and dairy and grains, which “can be inflammatory in some people,” and focusing on whole, nutrient-rich foods – all in keeping with the AIP principles – should have positive effects on the microbiome, overall health, and likely AD as well, he said.

Across the board, Dr. Lio recommends vitamin D (at nationally recommended dosages) and probiotics. Vitamin D has been shown to significantly help a small percentage of patients with eczema, he said, so he advises patients that it’s worth a trial. “I tell patients that I don’t know how to pick that small group out, so let’s try for a few months and see,” he said. “Inevitably, a percentage of patients come back and say it makes a huge difference.”

Dr. Lio’s understanding and use of probiotics has been “dynamic” over the years. “The “best, most reliable evidence” that probiotics can improve AD symptoms comes with the use of multiple probiotic strains together, he said. Based on limited but growing literature, he ensures that recommended formulations for babies include Lactobacillus rhamnosus, and that formulations for adults include Lactobacillus salivarius.

Dr. Lio works closely with dietitians, hypnotherapists, and psychologists – and will occasionally refer interested patients with AD to a Chinese medicine practitioner who personalizes the use of herbal formulations.

He reported no relevant disclosures.

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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

MONTREAL – Ocular surface disease (OSD) in patients with atopic dermatitis (AD) treated with dupilumab may be exacerbated rather than caused by the therapy, according to a study presented at the annual meeting of the International Society of Atopic Dermatitis.

In a prospective trial of 69 patients with AD starting dupilumab (Dupixent), baseline OSD was found in 91.3%, with about half of these patients reporting no symptoms, said investigator Roselie Achten, MD, from the National Expertise Center for Atopic Dermatitis at University Medical Center Utrecht, the Netherlands. Among these patients, ophthalmologic assessment revealed no OSD in 6 patients and mild OSD in 37 patients, but moderate and severe disease in 20 and 6 patients, respectively, she said, adding that 71% of the group also reported allergic conjunctivitis at baseline.

The patients enrolled in the study who started dupilumab were aged 36-38 years, with Eczema Area and Severity Index (EASI) scores of 14.7-16.5. Baseline ocular surface health was assessed with the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. Tear fluid was collected to analyze biomarkers and dupilumab levels, and impression cytology was performed to collect conjunctival tissue cells for analysis of goblet cells. These measurements were repeated at 4 and 28 weeks after the start of therapy.

Over 28 weeks of treatment, 14.5% of patients experienced worsening of OSD, with worsening disease associated with a decline in the number of goblet cells. In addition, dupilumab treatment was associated with a significant decline in the production of Mucin5AC, suggesting a decline in function of the goblet cells. “Our hypothesis that the blocking effect of dupilumab on [interleukin-] IL-13 might lead to less goblet cells and less mucin production,” she explained.

In a subset of 48 patients, the researchers also detected significantly higher tear fluid dupilumab levels among those patients with more severe OSD, with comparable serum levels.

OSD has been reported in up to 34% of dupilumab-treated patients with AD and is the most frequently reported side-effect of this treatment, noted Dr. Achten. This side effect is not reported by other patients treated with dupilumab for other indications, she added, “suggesting that AD patients may have a predisposition to develop OSD during dupilumab treatment.”

Indeed, as recently noted by Vivian Shi, MD, from the department of dermatology, University of Arkansas for Medical Sciences, Little Rock, and colleagues, “for reasons not well understood, the incidence of conjunctivitis in dupilumab patients with asthma (0%-2.3%), chronic rhinosinusitis with nasal polyps (1.6%), or eosinophilic esophagitis (0%) is low to none; thus, patients with AD may be particularly susceptible.”

Dr. Achten said that dupilumab-treated patients with AD at her center are prescribed topical tacrolimus and ketotifen eye drops if they develop OSD.

Asked for comment, Melinda Gooderham, MD, who moderated the session, was impressed with the study. “I’d heard about the goblet cells, there were little bits of data here and there, but the tear analysis is something I hadn’t seen before. It was a nice series of experiments that pulled everything together,” she told this news organization. Dr. Gooderham, who is assistant professor at Queens University, in Kingston, Ontario, medical director at the SKiN Centre for Dermatology in Peterborough, Ontario, and consultant physician at Peterborough Regional Health Centre, said that she first began noticing dupilumab-related OSD as an early trial investigator for the drug. “When you put some patients on the drug it’s almost like tipping the balance – that little bit of mucin they’re dependent on is now reduced and it makes them more symptomatic,” she said.

Though she prescribes lubricating eye drops as prophylaxis for all her dupilumab-treated patients with AD, she recommends referring any patients who develop OSD to an ophthalmologist who is familiar with this specific side effect. “If they just see a random ophthalmologist who doesn’t know dupilumab, and doesn’t know the story around it, they could get any sort of diagnosis, or even be told to stop the medication altogether.”

The study was sponsored by Sanofi. Dr. Achten disclosed no other conflicts of interest. Dr. Gooderham is an investigator with Sanofi Genzyme for dupilumab.

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

MONTREAL – Ocular surface disease (OSD) in patients with atopic dermatitis (AD) treated with dupilumab may be exacerbated rather than caused by the therapy, according to a study presented at the annual meeting of the International Society of Atopic Dermatitis.

In a prospective trial of 69 patients with AD starting dupilumab (Dupixent), baseline OSD was found in 91.3%, with about half of these patients reporting no symptoms, said investigator Roselie Achten, MD, from the National Expertise Center for Atopic Dermatitis at University Medical Center Utrecht, the Netherlands. Among these patients, ophthalmologic assessment revealed no OSD in 6 patients and mild OSD in 37 patients, but moderate and severe disease in 20 and 6 patients, respectively, she said, adding that 71% of the group also reported allergic conjunctivitis at baseline.

The patients enrolled in the study who started dupilumab were aged 36-38 years, with Eczema Area and Severity Index (EASI) scores of 14.7-16.5. Baseline ocular surface health was assessed with the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. Tear fluid was collected to analyze biomarkers and dupilumab levels, and impression cytology was performed to collect conjunctival tissue cells for analysis of goblet cells. These measurements were repeated at 4 and 28 weeks after the start of therapy.

Over 28 weeks of treatment, 14.5% of patients experienced worsening of OSD, with worsening disease associated with a decline in the number of goblet cells. In addition, dupilumab treatment was associated with a significant decline in the production of Mucin5AC, suggesting a decline in function of the goblet cells. “Our hypothesis that the blocking effect of dupilumab on [interleukin-] IL-13 might lead to less goblet cells and less mucin production,” she explained.

In a subset of 48 patients, the researchers also detected significantly higher tear fluid dupilumab levels among those patients with more severe OSD, with comparable serum levels.

OSD has been reported in up to 34% of dupilumab-treated patients with AD and is the most frequently reported side-effect of this treatment, noted Dr. Achten. This side effect is not reported by other patients treated with dupilumab for other indications, she added, “suggesting that AD patients may have a predisposition to develop OSD during dupilumab treatment.”

Indeed, as recently noted by Vivian Shi, MD, from the department of dermatology, University of Arkansas for Medical Sciences, Little Rock, and colleagues, “for reasons not well understood, the incidence of conjunctivitis in dupilumab patients with asthma (0%-2.3%), chronic rhinosinusitis with nasal polyps (1.6%), or eosinophilic esophagitis (0%) is low to none; thus, patients with AD may be particularly susceptible.”

Dr. Achten said that dupilumab-treated patients with AD at her center are prescribed topical tacrolimus and ketotifen eye drops if they develop OSD.

Asked for comment, Melinda Gooderham, MD, who moderated the session, was impressed with the study. “I’d heard about the goblet cells, there were little bits of data here and there, but the tear analysis is something I hadn’t seen before. It was a nice series of experiments that pulled everything together,” she told this news organization. Dr. Gooderham, who is assistant professor at Queens University, in Kingston, Ontario, medical director at the SKiN Centre for Dermatology in Peterborough, Ontario, and consultant physician at Peterborough Regional Health Centre, said that she first began noticing dupilumab-related OSD as an early trial investigator for the drug. “When you put some patients on the drug it’s almost like tipping the balance – that little bit of mucin they’re dependent on is now reduced and it makes them more symptomatic,” she said.

Though she prescribes lubricating eye drops as prophylaxis for all her dupilumab-treated patients with AD, she recommends referring any patients who develop OSD to an ophthalmologist who is familiar with this specific side effect. “If they just see a random ophthalmologist who doesn’t know dupilumab, and doesn’t know the story around it, they could get any sort of diagnosis, or even be told to stop the medication altogether.”

The study was sponsored by Sanofi. Dr. Achten disclosed no other conflicts of interest. Dr. Gooderham is an investigator with Sanofi Genzyme for dupilumab.

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

MONTREAL – Ocular surface disease (OSD) in patients with atopic dermatitis (AD) treated with dupilumab may be exacerbated rather than caused by the therapy, according to a study presented at the annual meeting of the International Society of Atopic Dermatitis.

In a prospective trial of 69 patients with AD starting dupilumab (Dupixent), baseline OSD was found in 91.3%, with about half of these patients reporting no symptoms, said investigator Roselie Achten, MD, from the National Expertise Center for Atopic Dermatitis at University Medical Center Utrecht, the Netherlands. Among these patients, ophthalmologic assessment revealed no OSD in 6 patients and mild OSD in 37 patients, but moderate and severe disease in 20 and 6 patients, respectively, she said, adding that 71% of the group also reported allergic conjunctivitis at baseline.

The patients enrolled in the study who started dupilumab were aged 36-38 years, with Eczema Area and Severity Index (EASI) scores of 14.7-16.5. Baseline ocular surface health was assessed with the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. Tear fluid was collected to analyze biomarkers and dupilumab levels, and impression cytology was performed to collect conjunctival tissue cells for analysis of goblet cells. These measurements were repeated at 4 and 28 weeks after the start of therapy.

Over 28 weeks of treatment, 14.5% of patients experienced worsening of OSD, with worsening disease associated with a decline in the number of goblet cells. In addition, dupilumab treatment was associated with a significant decline in the production of Mucin5AC, suggesting a decline in function of the goblet cells. “Our hypothesis that the blocking effect of dupilumab on [interleukin-] IL-13 might lead to less goblet cells and less mucin production,” she explained.

In a subset of 48 patients, the researchers also detected significantly higher tear fluid dupilumab levels among those patients with more severe OSD, with comparable serum levels.

OSD has been reported in up to 34% of dupilumab-treated patients with AD and is the most frequently reported side-effect of this treatment, noted Dr. Achten. This side effect is not reported by other patients treated with dupilumab for other indications, she added, “suggesting that AD patients may have a predisposition to develop OSD during dupilumab treatment.”

Indeed, as recently noted by Vivian Shi, MD, from the department of dermatology, University of Arkansas for Medical Sciences, Little Rock, and colleagues, “for reasons not well understood, the incidence of conjunctivitis in dupilumab patients with asthma (0%-2.3%), chronic rhinosinusitis with nasal polyps (1.6%), or eosinophilic esophagitis (0%) is low to none; thus, patients with AD may be particularly susceptible.”

Dr. Achten said that dupilumab-treated patients with AD at her center are prescribed topical tacrolimus and ketotifen eye drops if they develop OSD.

Asked for comment, Melinda Gooderham, MD, who moderated the session, was impressed with the study. “I’d heard about the goblet cells, there were little bits of data here and there, but the tear analysis is something I hadn’t seen before. It was a nice series of experiments that pulled everything together,” she told this news organization. Dr. Gooderham, who is assistant professor at Queens University, in Kingston, Ontario, medical director at the SKiN Centre for Dermatology in Peterborough, Ontario, and consultant physician at Peterborough Regional Health Centre, said that she first began noticing dupilumab-related OSD as an early trial investigator for the drug. “When you put some patients on the drug it’s almost like tipping the balance – that little bit of mucin they’re dependent on is now reduced and it makes them more symptomatic,” she said.

Though she prescribes lubricating eye drops as prophylaxis for all her dupilumab-treated patients with AD, she recommends referring any patients who develop OSD to an ophthalmologist who is familiar with this specific side effect. “If they just see a random ophthalmologist who doesn’t know dupilumab, and doesn’t know the story around it, they could get any sort of diagnosis, or even be told to stop the medication altogether.”

The study was sponsored by Sanofi. Dr. Achten disclosed no other conflicts of interest. Dr. Gooderham is an investigator with Sanofi Genzyme for dupilumab.

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

Key clinical point: Patients with atopic dermatitis (AD) have a 50% higher chance of developing alcohol use disorder (AUD) than people without AD and should be screened when appropriate.

Major finding: Patients with AD had a significantly higher chance of developing AUD (odds ratio 1.50; P < .001) than controls without AD.

Study details: Findings are from the All of Us cohort including 11,752 patients with AD and 47,008 matched controls.

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

Source: Fan R et al. Alcohol use disorder among adults with atopic dermatitis: A case-control study in the All of Us research program. J Am Acad Dermatol. 2022 (Sep 20). Doi: 10.1016/j.jaad.2022.09.015

Key clinical point: Patients with atopic dermatitis (AD) have a 50% higher chance of developing alcohol use disorder (AUD) than people without AD and should be screened when appropriate.

Major finding: Patients with AD had a significantly higher chance of developing AUD (odds ratio 1.50; P < .001) than controls without AD.

Study details: Findings are from the All of Us cohort including 11,752 patients with AD and 47,008 matched controls.

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

Source: Fan R et al. Alcohol use disorder among adults with atopic dermatitis: A case-control study in the All of Us research program. J Am Acad Dermatol. 2022 (Sep 20). Doi: 10.1016/j.jaad.2022.09.015

Key clinical point: Patients with atopic dermatitis (AD) have a 50% higher chance of developing alcohol use disorder (AUD) than people without AD and should be screened when appropriate.

Major finding: Patients with AD had a significantly higher chance of developing AUD (odds ratio 1.50; P < .001) than controls without AD.

Study details: Findings are from the All of Us cohort including 11,752 patients with AD and 47,008 matched controls.

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

Source: Fan R et al. Alcohol use disorder among adults with atopic dermatitis: A case-control study in the All of Us research program. J Am Acad Dermatol. 2022 (Sep 20). Doi: 10.1016/j.jaad.2022.09.015