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The skin phenotype of new-onset pediatric atopic dermatitis differs substantially from that in adult AD, according to an assessment of biopsy findings in infants and children.
The study findings have important therapeutic implications, especially in light of the fact that much of the work in this area has been based on adult biomarkers, reflecting “decades of disease activity and chronic use of immunosuppressants in adults,” the investigators reported. Little is known about alterations in early lesions in children, which limits the advancement of targeted therapies, Hitokazu Esaki, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported online in the Journal of Allergy and Clinical Immunology (2016 Sep 22. doi: 10.1016/j.jaci.2016.07.013).
To characterize early pediatric AD skin phenotype, the investigators assessed lesional and nonlesional biopsies from 19 children under age 5 years (mean, 1.3 years) within 6 months of moderate to severe disease onset, as well as those from age-matched controls and adults, and found that, compared with adult AD, early AD involves comparable or greater epidermal hyperplasia and cellular infiltration, similar strong activation of Th2 and Th22 axes, and some Th1 skewing.
In addition, early AD involves significantly higher induction of Th17-related cytokines, compared with adult AD. Expression of filaggrin – an abundant barrier differentiation protein – was similar in AD and healthy children, whereas down-regulation is characteristic in adult AD, the investigators noted.
Nonlesional skin biopsies from the children showed both higher levels of inflammation and epidermal proliferation markers, they said.
The “surprising findings” of an early multicytokine response in new-onset pediatric AD, characterized by marked Th17, Th9, Th2, and Th22 activation, suggest that targeting of multiple cytokine axes may be needed in children with early-onset AD, one of the lead authors on the study, Emma Guttman-Yassky, MD, also of the Icahn School of Medicine at Mount Sinai, said in an interview.
Dr. Guttman-Yassky, who noted that the study was conducted in close collaboration with Amy S. Paller, MD, of Northwestern University, Chicago, explained that early AD, compared with adult AD, involves differential immune skewing and barrier responses with features that are in some ways comparable to those of psoriasis – particularly with respect to the consistently higher levels of Th17-related mediators in childhood AD, as psoriasis is considered a Th17-centered disease.
Further, the findings with respect to filaggrin represent another important aspect of the study, she said, noting that they represent a possible challenge to the notion that filaggrin is integral to disease elicitation and instigation of the “atopic march.”
The study findings may suggest novel targets for pediatric AD, and they also suggest a need for early immune intervention, not only to treat the AD, but also to prevent the atopic march, she said.
“These findings are likely to result in both different understanding of AD onset and distinct treatment approaches for infants and children,” she and her colleagues concluded.
This work was funded by a research grant from the LEO Foundation. Individual authors were supported by grants from the National Center for Advancing Translational Sciences and the National Institutes of Health Clinical and Translational Science Award program. Dr. Esaki reported having no disclosures. Dr. Guttman-Yassky reported financial relationships with numerous pharmaceutical companies.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Severe AD places a huge burden on patients, their families, and society in terms of health care dollars spent and lost work days. Considering the prevalence of AD, both families and dermatologists find it understandably frustrating that we have limited and often ineffective tools to treat severe AD in children. Change may be around the corner.
This study by Esaki et al. sheds critical light on the pathogenesis of early onset AD in children and we hope it will set the stage to revolutionize the treatment of AD using the paradigm of psoriasis as a model. Using lesional and nonlesional biopsies from 19 children under age 5 obtained during the first 6 months of onset of AD, Esaki et al. have demonstrated that children with AD have a multicytokine inflammatory infiltrate with Th17 predominance. This sets the stage for biologics focused on the Th17 pathway in these children, although multimodal therapy to address different cytokines may ultimately be required.
The investigators also found that children with AD had similar filaggrin expression compared to control children, implying that atopic dermatitis is at its heart an immunologic disorder rather than a barrier defect although we will likely continue to learn more about this fine balance.
As pediatric dermatologists on the front line caring for patients with severe AD, we welcome further studies and especially look forward to effective treatments for our patients who might finally experience relief of itch, clear skin, and a good night’s sleep.
A. Yasmine Kirkorian, MD, and Kalyani Marathe, MD, are pediatric dermatologists at Children’s National Health System, in the departments of dermatology and pediatrics at George Washington University, Washington, DC. They are on the editorial advisory board of Dermatology News. They had no disclosures.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Severe AD places a huge burden on patients, their families, and society in terms of health care dollars spent and lost work days. Considering the prevalence of AD, both families and dermatologists find it understandably frustrating that we have limited and often ineffective tools to treat severe AD in children. Change may be around the corner.
This study by Esaki et al. sheds critical light on the pathogenesis of early onset AD in children and we hope it will set the stage to revolutionize the treatment of AD using the paradigm of psoriasis as a model. Using lesional and nonlesional biopsies from 19 children under age 5 obtained during the first 6 months of onset of AD, Esaki et al. have demonstrated that children with AD have a multicytokine inflammatory infiltrate with Th17 predominance. This sets the stage for biologics focused on the Th17 pathway in these children, although multimodal therapy to address different cytokines may ultimately be required.
The investigators also found that children with AD had similar filaggrin expression compared to control children, implying that atopic dermatitis is at its heart an immunologic disorder rather than a barrier defect although we will likely continue to learn more about this fine balance.
As pediatric dermatologists on the front line caring for patients with severe AD, we welcome further studies and especially look forward to effective treatments for our patients who might finally experience relief of itch, clear skin, and a good night’s sleep.
A. Yasmine Kirkorian, MD, and Kalyani Marathe, MD, are pediatric dermatologists at Children’s National Health System, in the departments of dermatology and pediatrics at George Washington University, Washington, DC. They are on the editorial advisory board of Dermatology News. They had no disclosures.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Severe AD places a huge burden on patients, their families, and society in terms of health care dollars spent and lost work days. Considering the prevalence of AD, both families and dermatologists find it understandably frustrating that we have limited and often ineffective tools to treat severe AD in children. Change may be around the corner.
This study by Esaki et al. sheds critical light on the pathogenesis of early onset AD in children and we hope it will set the stage to revolutionize the treatment of AD using the paradigm of psoriasis as a model. Using lesional and nonlesional biopsies from 19 children under age 5 obtained during the first 6 months of onset of AD, Esaki et al. have demonstrated that children with AD have a multicytokine inflammatory infiltrate with Th17 predominance. This sets the stage for biologics focused on the Th17 pathway in these children, although multimodal therapy to address different cytokines may ultimately be required.
The investigators also found that children with AD had similar filaggrin expression compared to control children, implying that atopic dermatitis is at its heart an immunologic disorder rather than a barrier defect although we will likely continue to learn more about this fine balance.
As pediatric dermatologists on the front line caring for patients with severe AD, we welcome further studies and especially look forward to effective treatments for our patients who might finally experience relief of itch, clear skin, and a good night’s sleep.
A. Yasmine Kirkorian, MD, and Kalyani Marathe, MD, are pediatric dermatologists at Children’s National Health System, in the departments of dermatology and pediatrics at George Washington University, Washington, DC. They are on the editorial advisory board of Dermatology News. They had no disclosures.
The skin phenotype of new-onset pediatric atopic dermatitis differs substantially from that in adult AD, according to an assessment of biopsy findings in infants and children.
The study findings have important therapeutic implications, especially in light of the fact that much of the work in this area has been based on adult biomarkers, reflecting “decades of disease activity and chronic use of immunosuppressants in adults,” the investigators reported. Little is known about alterations in early lesions in children, which limits the advancement of targeted therapies, Hitokazu Esaki, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported online in the Journal of Allergy and Clinical Immunology (2016 Sep 22. doi: 10.1016/j.jaci.2016.07.013).
To characterize early pediatric AD skin phenotype, the investigators assessed lesional and nonlesional biopsies from 19 children under age 5 years (mean, 1.3 years) within 6 months of moderate to severe disease onset, as well as those from age-matched controls and adults, and found that, compared with adult AD, early AD involves comparable or greater epidermal hyperplasia and cellular infiltration, similar strong activation of Th2 and Th22 axes, and some Th1 skewing.
In addition, early AD involves significantly higher induction of Th17-related cytokines, compared with adult AD. Expression of filaggrin – an abundant barrier differentiation protein – was similar in AD and healthy children, whereas down-regulation is characteristic in adult AD, the investigators noted.
Nonlesional skin biopsies from the children showed both higher levels of inflammation and epidermal proliferation markers, they said.
The “surprising findings” of an early multicytokine response in new-onset pediatric AD, characterized by marked Th17, Th9, Th2, and Th22 activation, suggest that targeting of multiple cytokine axes may be needed in children with early-onset AD, one of the lead authors on the study, Emma Guttman-Yassky, MD, also of the Icahn School of Medicine at Mount Sinai, said in an interview.
Dr. Guttman-Yassky, who noted that the study was conducted in close collaboration with Amy S. Paller, MD, of Northwestern University, Chicago, explained that early AD, compared with adult AD, involves differential immune skewing and barrier responses with features that are in some ways comparable to those of psoriasis – particularly with respect to the consistently higher levels of Th17-related mediators in childhood AD, as psoriasis is considered a Th17-centered disease.
Further, the findings with respect to filaggrin represent another important aspect of the study, she said, noting that they represent a possible challenge to the notion that filaggrin is integral to disease elicitation and instigation of the “atopic march.”
The study findings may suggest novel targets for pediatric AD, and they also suggest a need for early immune intervention, not only to treat the AD, but also to prevent the atopic march, she said.
“These findings are likely to result in both different understanding of AD onset and distinct treatment approaches for infants and children,” she and her colleagues concluded.
This work was funded by a research grant from the LEO Foundation. Individual authors were supported by grants from the National Center for Advancing Translational Sciences and the National Institutes of Health Clinical and Translational Science Award program. Dr. Esaki reported having no disclosures. Dr. Guttman-Yassky reported financial relationships with numerous pharmaceutical companies.
The skin phenotype of new-onset pediatric atopic dermatitis differs substantially from that in adult AD, according to an assessment of biopsy findings in infants and children.
The study findings have important therapeutic implications, especially in light of the fact that much of the work in this area has been based on adult biomarkers, reflecting “decades of disease activity and chronic use of immunosuppressants in adults,” the investigators reported. Little is known about alterations in early lesions in children, which limits the advancement of targeted therapies, Hitokazu Esaki, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues reported online in the Journal of Allergy and Clinical Immunology (2016 Sep 22. doi: 10.1016/j.jaci.2016.07.013).
To characterize early pediatric AD skin phenotype, the investigators assessed lesional and nonlesional biopsies from 19 children under age 5 years (mean, 1.3 years) within 6 months of moderate to severe disease onset, as well as those from age-matched controls and adults, and found that, compared with adult AD, early AD involves comparable or greater epidermal hyperplasia and cellular infiltration, similar strong activation of Th2 and Th22 axes, and some Th1 skewing.
In addition, early AD involves significantly higher induction of Th17-related cytokines, compared with adult AD. Expression of filaggrin – an abundant barrier differentiation protein – was similar in AD and healthy children, whereas down-regulation is characteristic in adult AD, the investigators noted.
Nonlesional skin biopsies from the children showed both higher levels of inflammation and epidermal proliferation markers, they said.
The “surprising findings” of an early multicytokine response in new-onset pediatric AD, characterized by marked Th17, Th9, Th2, and Th22 activation, suggest that targeting of multiple cytokine axes may be needed in children with early-onset AD, one of the lead authors on the study, Emma Guttman-Yassky, MD, also of the Icahn School of Medicine at Mount Sinai, said in an interview.
Dr. Guttman-Yassky, who noted that the study was conducted in close collaboration with Amy S. Paller, MD, of Northwestern University, Chicago, explained that early AD, compared with adult AD, involves differential immune skewing and barrier responses with features that are in some ways comparable to those of psoriasis – particularly with respect to the consistently higher levels of Th17-related mediators in childhood AD, as psoriasis is considered a Th17-centered disease.
Further, the findings with respect to filaggrin represent another important aspect of the study, she said, noting that they represent a possible challenge to the notion that filaggrin is integral to disease elicitation and instigation of the “atopic march.”
The study findings may suggest novel targets for pediatric AD, and they also suggest a need for early immune intervention, not only to treat the AD, but also to prevent the atopic march, she said.
“These findings are likely to result in both different understanding of AD onset and distinct treatment approaches for infants and children,” she and her colleagues concluded.
This work was funded by a research grant from the LEO Foundation. Individual authors were supported by grants from the National Center for Advancing Translational Sciences and the National Institutes of Health Clinical and Translational Science Award program. Dr. Esaki reported having no disclosures. Dr. Guttman-Yassky reported financial relationships with numerous pharmaceutical companies.
FROM THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Key clinical point: The skin phenotype of new-onset pediatric atopic dermatitis differs substantially from that in adult AD, which has important therapeutic implications, according to a study of biopsy findings in infants and children.
Major finding: Early AD involves significantly higher induction of Th17-related cytokines, compared with adult AD.
Data source: An analysis of biopsies from 19 children with AD.
Disclosures: This work was funded by a research grant from the LEO Foundation. Individual authors were supported by grants from the National Center for Advancing Translational Sciences and the National Institutes of Health Clinical and Translational Science Award program. Dr. Esaki reported having no disclosures. Dr. Guttman-Yassky reported financial relationships with numerous pharmaceutical companies.
