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Progression through the “atopic march” varies by age of atopic dermatitis (AD) onset, and is more pronounced among patients aged two years and younger, results from a large, retrospective cohort study demonstrated.

Dr. Joy Wan, a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia.
Dr. Joy Wan

“The atopic march is characterized by a progression from atopic dermatitis, usually early in childhood, to subsequent development of allergic rhinitis and asthma, lead study author Joy Wan, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is thought that the skin acts as the site of primary sensitization through a defective epithelial barrier, which then allows for allergic sensitization to occur in the airways. It is estimated that 30%-60% of AD patients go on to develop asthma and/or allergic rhinitis. However, not all patients complete the so-called atopic march, and this variation in the risk of asthma and allergic rhinitis among AD patients is not very well understood. Better ways to risk stratify these patients are needed.”

One possible explanation for this variation in the risk of atopy in AD patients could be the timing of their dermatitis onset. “We know that atopic dermatitis begins in infancy, but it can start at any age,” said Dr. Wan, who is a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia. “There has been a distinction between early-onset versus late-onset AD. Some past studies have also suggested that there is an increased risk of asthma and allergic rhinitis in children who have early-onset AD before the age of 1 or 2. This suggests that perhaps the model of the atopic march varies between early- and late-onset AD. However, past studies have had several limitations. They’ve often had short durations of follow-up, they’ve only examined narrow ranges of age of onset for AD, and most of them have been designed to primarily evaluate other exposures and outcomes, rather than looking at the timing of AD onset itself.”

For the current study, Dr. Wan and her associates set out to examine the risk of seasonal allergies and asthma among children with AD with respect to the age of AD onset. They used data from the Pediatric Eczema Elective Registry (PEER), an ongoing, prospective U.S. cohort of more than 7,700 children with physician-confirmed AD (JAMA Dermatol. 2014 Jun;150:593-600). All registry participants had used pimecrolimus cream in the past, but children with lymphoproliferative disease were excluded from the registry, as were those with malignancy or those who required the use of systemic immunosuppression.

The researchers evaluated 3,966 subjects in PEER with at least 3 years of follow-up. The exposure of interest was age of AD onset, and they divided patients into three broad age categories: early onset (age 2 years or younger), mid onset (3-7 years), and late onset (8-17 years). Primary outcomes were prevalent seasonal allergies and asthma at the time of registry enrollment, and incident seasonal allergies and asthma during follow-up, assessed via patient surveys every 3 years.

 

 



The study population included high proportions of white and black children, and there was a slight predominance of females. The median age at PEER enrollment increased with advancing age of AD onset (5.2 years in the early-onset group vs. 8.2 years in the mid-onset group and 13.1 years in the late-onset group), while the duration of follow-up was fairly similar across the three groups (a median of about 8.3 months). Family history of AD was common across all three groups, while patients in the late-onset group tended to have better control of their AD, compared with their younger counterparts.

At baseline, the prevalence of seasonal allergies was highest among the early-onset group at 74.6%, compared with 69.9% among the mid-onset group and 70.1% among the late-onset group. After adjusting for sex, race, and age at registry enrollment, the relative risk for prevalent seasonal allergies was 9% lower in the mid-onset group (0.91) and 18% lower in the late-onset group (0.82), compared with those in the early-onset group. Next, Dr. Wan and her associates calculated the incidence of seasonal allergies among 1,054 patients who did not have allergies at baseline. The cumulative incidence was highest among the early-onset group (56.1%), followed by the mid-onset group (46.8%), and the late-onset group (30.6%). On adjusted analysis, the relative risk for seasonal allergies among patients who had no allergies at baseline was 18% lower in the mid-onset group (0.82) and 36% lower in the late-onset group (0.64), compared with those in the early-onset group.

In the analysis of asthma risk by age of AD onset, prevalence was highest among patients in the early-onset group at 51.5%, compared with 44.7% among the mid-onset age group and 43% among the late-onset age group. On adjusted analysis, the relative risk for asthma was 15% lower in the mid-onset group (0.85) and 29% lower in the late-onset group (0.71), compared with those in the early-onset group. Meanwhile, the cumulative incidence of asthma among patients without asthma at baseline was also highest in the early-onset group (39.2%), compared with 31.9% in the mid-onset group and 29.9% in the late-onset group.


On adjusted analysis, the relative risk for asthma among this subset of patients was 4% lower in the mid-onset group (0.96) and 8% lower in the late-onset group (0.92), compared with those in the early-onset group, a difference that was not statistically significant. “One possible explanation for this is that asthma tends to develop soon after AD does, and the rates of developing asthma later on, as detected by our study, are nondifferential,” Dr. Wan said. “Another possibility is that the impact of early-onset versus late-onset AD is just different for asthma than it is for seasonal allergies.”

She acknowledged certain limitations of the study, including the risk of misclassification bias and limitations in recall with self-reported data, and the fact that the findings may not be generalizable to all patients with AD.

“Future studies with longer follow-up and studies of adult-onset AD will help extend our findings,” she concluded. “Nevertheless, our findings may inform how we risk stratify patients for AD treatment or atopic march prevention efforts in the future.”

PEER is funded by a grant from Valeant Pharmaceuticals, but Valeant had no role in this study. Dr. Wan reported having no financial disclosures. The study won an award at the meeting for best research presented by a dermatology resident or fellow.

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Progression through the “atopic march” varies by age of atopic dermatitis (AD) onset, and is more pronounced among patients aged two years and younger, results from a large, retrospective cohort study demonstrated.

Dr. Joy Wan, a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia.
Dr. Joy Wan

“The atopic march is characterized by a progression from atopic dermatitis, usually early in childhood, to subsequent development of allergic rhinitis and asthma, lead study author Joy Wan, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is thought that the skin acts as the site of primary sensitization through a defective epithelial barrier, which then allows for allergic sensitization to occur in the airways. It is estimated that 30%-60% of AD patients go on to develop asthma and/or allergic rhinitis. However, not all patients complete the so-called atopic march, and this variation in the risk of asthma and allergic rhinitis among AD patients is not very well understood. Better ways to risk stratify these patients are needed.”

One possible explanation for this variation in the risk of atopy in AD patients could be the timing of their dermatitis onset. “We know that atopic dermatitis begins in infancy, but it can start at any age,” said Dr. Wan, who is a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia. “There has been a distinction between early-onset versus late-onset AD. Some past studies have also suggested that there is an increased risk of asthma and allergic rhinitis in children who have early-onset AD before the age of 1 or 2. This suggests that perhaps the model of the atopic march varies between early- and late-onset AD. However, past studies have had several limitations. They’ve often had short durations of follow-up, they’ve only examined narrow ranges of age of onset for AD, and most of them have been designed to primarily evaluate other exposures and outcomes, rather than looking at the timing of AD onset itself.”

For the current study, Dr. Wan and her associates set out to examine the risk of seasonal allergies and asthma among children with AD with respect to the age of AD onset. They used data from the Pediatric Eczema Elective Registry (PEER), an ongoing, prospective U.S. cohort of more than 7,700 children with physician-confirmed AD (JAMA Dermatol. 2014 Jun;150:593-600). All registry participants had used pimecrolimus cream in the past, but children with lymphoproliferative disease were excluded from the registry, as were those with malignancy or those who required the use of systemic immunosuppression.

The researchers evaluated 3,966 subjects in PEER with at least 3 years of follow-up. The exposure of interest was age of AD onset, and they divided patients into three broad age categories: early onset (age 2 years or younger), mid onset (3-7 years), and late onset (8-17 years). Primary outcomes were prevalent seasonal allergies and asthma at the time of registry enrollment, and incident seasonal allergies and asthma during follow-up, assessed via patient surveys every 3 years.

 

 



The study population included high proportions of white and black children, and there was a slight predominance of females. The median age at PEER enrollment increased with advancing age of AD onset (5.2 years in the early-onset group vs. 8.2 years in the mid-onset group and 13.1 years in the late-onset group), while the duration of follow-up was fairly similar across the three groups (a median of about 8.3 months). Family history of AD was common across all three groups, while patients in the late-onset group tended to have better control of their AD, compared with their younger counterparts.

At baseline, the prevalence of seasonal allergies was highest among the early-onset group at 74.6%, compared with 69.9% among the mid-onset group and 70.1% among the late-onset group. After adjusting for sex, race, and age at registry enrollment, the relative risk for prevalent seasonal allergies was 9% lower in the mid-onset group (0.91) and 18% lower in the late-onset group (0.82), compared with those in the early-onset group. Next, Dr. Wan and her associates calculated the incidence of seasonal allergies among 1,054 patients who did not have allergies at baseline. The cumulative incidence was highest among the early-onset group (56.1%), followed by the mid-onset group (46.8%), and the late-onset group (30.6%). On adjusted analysis, the relative risk for seasonal allergies among patients who had no allergies at baseline was 18% lower in the mid-onset group (0.82) and 36% lower in the late-onset group (0.64), compared with those in the early-onset group.

In the analysis of asthma risk by age of AD onset, prevalence was highest among patients in the early-onset group at 51.5%, compared with 44.7% among the mid-onset age group and 43% among the late-onset age group. On adjusted analysis, the relative risk for asthma was 15% lower in the mid-onset group (0.85) and 29% lower in the late-onset group (0.71), compared with those in the early-onset group. Meanwhile, the cumulative incidence of asthma among patients without asthma at baseline was also highest in the early-onset group (39.2%), compared with 31.9% in the mid-onset group and 29.9% in the late-onset group.


On adjusted analysis, the relative risk for asthma among this subset of patients was 4% lower in the mid-onset group (0.96) and 8% lower in the late-onset group (0.92), compared with those in the early-onset group, a difference that was not statistically significant. “One possible explanation for this is that asthma tends to develop soon after AD does, and the rates of developing asthma later on, as detected by our study, are nondifferential,” Dr. Wan said. “Another possibility is that the impact of early-onset versus late-onset AD is just different for asthma than it is for seasonal allergies.”

She acknowledged certain limitations of the study, including the risk of misclassification bias and limitations in recall with self-reported data, and the fact that the findings may not be generalizable to all patients with AD.

“Future studies with longer follow-up and studies of adult-onset AD will help extend our findings,” she concluded. “Nevertheless, our findings may inform how we risk stratify patients for AD treatment or atopic march prevention efforts in the future.”

PEER is funded by a grant from Valeant Pharmaceuticals, but Valeant had no role in this study. Dr. Wan reported having no financial disclosures. The study won an award at the meeting for best research presented by a dermatology resident or fellow.

 

Progression through the “atopic march” varies by age of atopic dermatitis (AD) onset, and is more pronounced among patients aged two years and younger, results from a large, retrospective cohort study demonstrated.

Dr. Joy Wan, a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia.
Dr. Joy Wan

“The atopic march is characterized by a progression from atopic dermatitis, usually early in childhood, to subsequent development of allergic rhinitis and asthma, lead study author Joy Wan, MD, said at the annual meeting of the Society for Pediatric Dermatology. “It is thought that the skin acts as the site of primary sensitization through a defective epithelial barrier, which then allows for allergic sensitization to occur in the airways. It is estimated that 30%-60% of AD patients go on to develop asthma and/or allergic rhinitis. However, not all patients complete the so-called atopic march, and this variation in the risk of asthma and allergic rhinitis among AD patients is not very well understood. Better ways to risk stratify these patients are needed.”

One possible explanation for this variation in the risk of atopy in AD patients could be the timing of their dermatitis onset. “We know that atopic dermatitis begins in infancy, but it can start at any age,” said Dr. Wan, who is a fellow in the section of pediatric dermatology at the Children’s Hospital of Philadelphia. “There has been a distinction between early-onset versus late-onset AD. Some past studies have also suggested that there is an increased risk of asthma and allergic rhinitis in children who have early-onset AD before the age of 1 or 2. This suggests that perhaps the model of the atopic march varies between early- and late-onset AD. However, past studies have had several limitations. They’ve often had short durations of follow-up, they’ve only examined narrow ranges of age of onset for AD, and most of them have been designed to primarily evaluate other exposures and outcomes, rather than looking at the timing of AD onset itself.”

For the current study, Dr. Wan and her associates set out to examine the risk of seasonal allergies and asthma among children with AD with respect to the age of AD onset. They used data from the Pediatric Eczema Elective Registry (PEER), an ongoing, prospective U.S. cohort of more than 7,700 children with physician-confirmed AD (JAMA Dermatol. 2014 Jun;150:593-600). All registry participants had used pimecrolimus cream in the past, but children with lymphoproliferative disease were excluded from the registry, as were those with malignancy or those who required the use of systemic immunosuppression.

The researchers evaluated 3,966 subjects in PEER with at least 3 years of follow-up. The exposure of interest was age of AD onset, and they divided patients into three broad age categories: early onset (age 2 years or younger), mid onset (3-7 years), and late onset (8-17 years). Primary outcomes were prevalent seasonal allergies and asthma at the time of registry enrollment, and incident seasonal allergies and asthma during follow-up, assessed via patient surveys every 3 years.

 

 



The study population included high proportions of white and black children, and there was a slight predominance of females. The median age at PEER enrollment increased with advancing age of AD onset (5.2 years in the early-onset group vs. 8.2 years in the mid-onset group and 13.1 years in the late-onset group), while the duration of follow-up was fairly similar across the three groups (a median of about 8.3 months). Family history of AD was common across all three groups, while patients in the late-onset group tended to have better control of their AD, compared with their younger counterparts.

At baseline, the prevalence of seasonal allergies was highest among the early-onset group at 74.6%, compared with 69.9% among the mid-onset group and 70.1% among the late-onset group. After adjusting for sex, race, and age at registry enrollment, the relative risk for prevalent seasonal allergies was 9% lower in the mid-onset group (0.91) and 18% lower in the late-onset group (0.82), compared with those in the early-onset group. Next, Dr. Wan and her associates calculated the incidence of seasonal allergies among 1,054 patients who did not have allergies at baseline. The cumulative incidence was highest among the early-onset group (56.1%), followed by the mid-onset group (46.8%), and the late-onset group (30.6%). On adjusted analysis, the relative risk for seasonal allergies among patients who had no allergies at baseline was 18% lower in the mid-onset group (0.82) and 36% lower in the late-onset group (0.64), compared with those in the early-onset group.

In the analysis of asthma risk by age of AD onset, prevalence was highest among patients in the early-onset group at 51.5%, compared with 44.7% among the mid-onset age group and 43% among the late-onset age group. On adjusted analysis, the relative risk for asthma was 15% lower in the mid-onset group (0.85) and 29% lower in the late-onset group (0.71), compared with those in the early-onset group. Meanwhile, the cumulative incidence of asthma among patients without asthma at baseline was also highest in the early-onset group (39.2%), compared with 31.9% in the mid-onset group and 29.9% in the late-onset group.


On adjusted analysis, the relative risk for asthma among this subset of patients was 4% lower in the mid-onset group (0.96) and 8% lower in the late-onset group (0.92), compared with those in the early-onset group, a difference that was not statistically significant. “One possible explanation for this is that asthma tends to develop soon after AD does, and the rates of developing asthma later on, as detected by our study, are nondifferential,” Dr. Wan said. “Another possibility is that the impact of early-onset versus late-onset AD is just different for asthma than it is for seasonal allergies.”

She acknowledged certain limitations of the study, including the risk of misclassification bias and limitations in recall with self-reported data, and the fact that the findings may not be generalizable to all patients with AD.

“Future studies with longer follow-up and studies of adult-onset AD will help extend our findings,” she concluded. “Nevertheless, our findings may inform how we risk stratify patients for AD treatment or atopic march prevention efforts in the future.”

PEER is funded by a grant from Valeant Pharmaceuticals, but Valeant had no role in this study. Dr. Wan reported having no financial disclosures. The study won an award at the meeting for best research presented by a dermatology resident or fellow.

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