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Research in Review

Eczema Review

December 2017

A review of recent news, research, and treatment related to eczema.

Progression From Eczema to Asthma and Allergies 

child itching faceChildren with both atopic dermatitis (AD) and allergic sensitization at age 1 year have a more than 7-fold increased risk for developing asthma as well as an increased risk for developing food allergies by age 3 years, according to a recent study, published in the Journal of Allergy and Clinical Immunology.
 

 The study included 2311 children who underwent skin prick testing at age 1 year and were assessed for AD. Children who produced a 2 mm or larger wheal than that elicited by controls in response to 10 inhalant or food allergens were considered sensitized. At age 3, they were evaluated for asthma, allergic rhinitis, food allergy, and AD.

After adjusting for common confounders, the researchers found that AD without allergic sensitization was not associated with an increased risk of asthma at age 3 years (relative risk [RR], 0.46). However, AD with allergic sensitization was associated with a more than 7-fold increased risk of asthma (RR, 7.04). AD and allergic sensitization had significant interactions on the additive (relative excess risk 5.06) and multiplicative (ratio of RRs 5.80) scales in association with asthma risk. Additionally, there was a positive additive interaction between AD and allergic sensitization in their effects on the risk for developing food allergies (relative excess risk 15.11).

“Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years,” the researchers concluded. 

 

Reference

Tran MM, Lefebvre DL, Dharma C, et al; Canadian Healthy Infant Longitudinal Development Study investigators. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study [published online November 1, 2017]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2017.08.024

 

depression holding legsAD Increases Depression, Anxiety Among Patients 
 

A recent survey by the National Eczema Association (NEA) found that patients with atopic dermatitis (AD) often report a depression or anxiety diagnosis. The NEA surveyed 545 patients with AD. 

Based on the study, it is estimated that more than 30% of adults with AD are diagnosed with anxiety/depression. The prevalence of AD in adults in the United States is estimated to be 7.2% or 18 million. Adults in the United States with AD say that it impacts almost every area of their lives, including profession, intimate relationships, sleep quality, and overall well-being. 

“Atopic dermatitis is a complex disease as this survey shows,” said Julie Block, president and chief executive officer of NEA. “Research reveals this form of eczema goes well beyond what you see on the skin. Chronic inflammation, symptoms such as unbearable itch, being severely allergic to the world around you—these all profoundly affect the quality of life of people with AD.”

To learn more about eczema and mental health and access resources from the NEA, go to https://nationaleczema.org/eczema-emotional-wellness/. 

Article continues on page 2

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breastfeedingBreastfeeding Intervention May Reduce Eczema Risk in Adolescence

 

A breastfeeding promotion intervention may reduce infants’ risk for flexural eczema during their adolescent years, according to a recent study published online in JAMA Pediatrics.

Atopic diseases such as atopic eczema, asthma, and low lung function are among the most common chronic conditions in children. However, it is not known whether a prolonged breastfeeding intervention influences the risk for these conditions later in life. Carsten Flohr, FRCP, PhD, of King’s College London, and colleagues conducted a follow-up study of the Promotion of Breastfeeding Intervention Trial (PROBIT), which recruited 17,046 healthy term infants from June 16, 1996 to December 31, 1997. Patients were placed in either the intervention group or the control group.

A data analysis was performed from May 9, 2016 to April 21, 2017, and the modified intention-to-treat analysis served as the primary analytic approach. The primary outcomes included spirometry and flexural eczema based on standardized skin examination by study pediatricians, and secondary outcomes included symptoms of flexural eczema within the last year.

Of 17,046 participants, 13,557 (79.5%) were followed up from September 15, 2012 to July 15, 2015. Mean participant age at follow-up was 16.2 years in the intervention group (n=7064) and 16.1 years in the control group (n=6493). Results indicated that 21 (0.3%) patients in the intervention group had flexural eczema upon skin examination compared with 43 (0.7%) patients in the control group.

Findings from the modified intention-to-treat analysis demonstrated that the risk for flexural eczema upon skin examination was 54% lower in the intervention group vs the control group. Furthermore, the rate of self-reported flexural eczema symptoms within the last year was lower in the intervention group vs the control group. However, the researchers noted that 95% CIs were wide and included the null.

All results remained similar following additional adjustment for baseline characteristics, on instrumental variable analysis, and following multiple imputation in all 17,046 participants.

“A breastfeeding promotion intervention reduced flexural dermatitis risk but had no detectable effect on lung function or questionnaire-derived measures of atopic eczema or asthma in adolescence in a setting where atopic eczema and allergies are rare,” the researchers concluded. 

 

Reference

Flohr C, Henderson AJ, Kramer MS, et al. Effect of an intervention to promote breastfeeding on asthma, lung function, and atopic eczema at age 16 years: follow-up of the PROBIT randomized trial [published online November 13, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.4064

 

itchy elbowPruritus in Patients AD: An Extended Analysis With Eczema Ointment
 

A poster presented at the recent Fall Clinical Dermatology Conference reported on the results of an extended analysis of crisaborole ointment (Eucrisa), a nonsteroidal phosphodiesterase-4 inhibitor for the treatment of mild to moderate AD. The researchers used the Severity of Pruritus Scale (SPS), a 4-point rating scale, ranging from 0 (none: no itching) to 3 (severe: bothersome itching/scratching which disturbs sleep), which was adapted from the Atopic Dermatitis Severity Index to quantify itch over a 24-hour recall period in the crisaborole phase 3 trials. 

In the prespecified analyses of these trials, pruritus data were analyzed using each SPS observation as a single measure. Subsequent SPS validation analysis determined that averaging at least 2 SPS observations is necessary to provide a reliable measure of pruritus severity, according to the researchers.

For the analysis, data from 2 identically designed, vehicle-controlled, double-blind, phase 3 trials (AD-301 and AD-302) were used. Time to improvement in pruritus (defined as an SPS score ≤1 with a ≥1-point improvement from baseline), proportion of patients experiencing improvement in pruritus by week, pruritus score by week, and proportion of responders by week (clinically important response [CIR] defined by a ≥0.19-point reduction in SPS score from baseline) were analyzed over a 4-week treatment period. A minimum of 2 SPS observations were averaged for each analysis to meet the test and retest reliability threshold of acceptability.

The intent-to-treat population included 759 patients (n=503 in the crisaborole group and n=256 in the vehicle group) for AD-301 and 763 patients (n=513 in the crisaborole group and n=250 in the vehicle group) for AD-302. Using the average of 2 daily SPS observations, crisaborole-treated patients had faster median time to improvement in pruritus than vehicle-treated patients in both trials (AD-301, 5.0 days vs 10.0 days; P<.0003; AD-302, 6.0 days vs 9.0 days; P=.0087). Using the average of all available SPS observations for each week (up to 14 observations), a greater proportion of crisaborole-treated patients showed improvement at week 4 than vehicle-treated patients (week 4: AD-301, 37.2% vs 21.2%; P<.0001; AD-302, 34.4% vs 20.6%; P=.0006); crisaborole-treated patients had lower pruritus scores at each week than vehicle-treated patients (P<.0001, all time points, both trials); and a higher proportion of crisaborole-treated patients were classified as responders per the CIR definition (week 4: AD-301, 74.7% vs 57.1%; P<.0001; AD-302, 71.9% vs 64.2%; P=.0828).

“These extended analyses, based on the validation analysis, show that crisaborole-treated patients experience improvement in pruritus earlier than vehicle-treated patients and that a greater proportion of crisaborole-treated patients experience improvement in pruritus and a clinically important pruritus response,” the researchers concluded. 

Reference

Yosipovitch G, Simpson E, Tan H, et al. The effect of crisaborole ointment, 2%, on pruritus in patients with atopic dermatitis (AD): an extended analysis. Presented at: Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV.

A review of recent news, research, and treatment related to eczema.

Progression From Eczema to Asthma and Allergies 

child itching faceChildren with both atopic dermatitis (AD) and allergic sensitization at age 1 year have a more than 7-fold increased risk for developing asthma as well as an increased risk for developing food allergies by age 3 years, according to a recent study, published in the Journal of Allergy and Clinical Immunology.
 

 The study included 2311 children who underwent skin prick testing at age 1 year and were assessed for AD. Children who produced a 2 mm or larger wheal than that elicited by controls in response to 10 inhalant or food allergens were considered sensitized. At age 3, they were evaluated for asthma, allergic rhinitis, food allergy, and AD.

After adjusting for common confounders, the researchers found that AD without allergic sensitization was not associated with an increased risk of asthma at age 3 years (relative risk [RR], 0.46). However, AD with allergic sensitization was associated with a more than 7-fold increased risk of asthma (RR, 7.04). AD and allergic sensitization had significant interactions on the additive (relative excess risk 5.06) and multiplicative (ratio of RRs 5.80) scales in association with asthma risk. Additionally, there was a positive additive interaction between AD and allergic sensitization in their effects on the risk for developing food allergies (relative excess risk 15.11).

“Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years,” the researchers concluded. 

 

Reference

Tran MM, Lefebvre DL, Dharma C, et al; Canadian Healthy Infant Longitudinal Development Study investigators. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study [published online November 1, 2017]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2017.08.024

 

depression holding legsAD Increases Depression, Anxiety Among Patients 
 

A recent survey by the National Eczema Association (NEA) found that patients with atopic dermatitis (AD) often report a depression or anxiety diagnosis. The NEA surveyed 545 patients with AD. 

Based on the study, it is estimated that more than 30% of adults with AD are diagnosed with anxiety/depression. The prevalence of AD in adults in the United States is estimated to be 7.2% or 18 million. Adults in the United States with AD say that it impacts almost every area of their lives, including profession, intimate relationships, sleep quality, and overall well-being. 

“Atopic dermatitis is a complex disease as this survey shows,” said Julie Block, president and chief executive officer of NEA. “Research reveals this form of eczema goes well beyond what you see on the skin. Chronic inflammation, symptoms such as unbearable itch, being severely allergic to the world around you—these all profoundly affect the quality of life of people with AD.”

To learn more about eczema and mental health and access resources from the NEA, go to https://nationaleczema.org/eczema-emotional-wellness/. 

Article continues on page 2

{{pagebreak}}

breastfeedingBreastfeeding Intervention May Reduce Eczema Risk in Adolescence

 

A breastfeeding promotion intervention may reduce infants’ risk for flexural eczema during their adolescent years, according to a recent study published online in JAMA Pediatrics.

Atopic diseases such as atopic eczema, asthma, and low lung function are among the most common chronic conditions in children. However, it is not known whether a prolonged breastfeeding intervention influences the risk for these conditions later in life. Carsten Flohr, FRCP, PhD, of King’s College London, and colleagues conducted a follow-up study of the Promotion of Breastfeeding Intervention Trial (PROBIT), which recruited 17,046 healthy term infants from June 16, 1996 to December 31, 1997. Patients were placed in either the intervention group or the control group.

A data analysis was performed from May 9, 2016 to April 21, 2017, and the modified intention-to-treat analysis served as the primary analytic approach. The primary outcomes included spirometry and flexural eczema based on standardized skin examination by study pediatricians, and secondary outcomes included symptoms of flexural eczema within the last year.

Of 17,046 participants, 13,557 (79.5%) were followed up from September 15, 2012 to July 15, 2015. Mean participant age at follow-up was 16.2 years in the intervention group (n=7064) and 16.1 years in the control group (n=6493). Results indicated that 21 (0.3%) patients in the intervention group had flexural eczema upon skin examination compared with 43 (0.7%) patients in the control group.

Findings from the modified intention-to-treat analysis demonstrated that the risk for flexural eczema upon skin examination was 54% lower in the intervention group vs the control group. Furthermore, the rate of self-reported flexural eczema symptoms within the last year was lower in the intervention group vs the control group. However, the researchers noted that 95% CIs were wide and included the null.

All results remained similar following additional adjustment for baseline characteristics, on instrumental variable analysis, and following multiple imputation in all 17,046 participants.

“A breastfeeding promotion intervention reduced flexural dermatitis risk but had no detectable effect on lung function or questionnaire-derived measures of atopic eczema or asthma in adolescence in a setting where atopic eczema and allergies are rare,” the researchers concluded. 

 

Reference

Flohr C, Henderson AJ, Kramer MS, et al. Effect of an intervention to promote breastfeeding on asthma, lung function, and atopic eczema at age 16 years: follow-up of the PROBIT randomized trial [published online November 13, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.4064

 

itchy elbowPruritus in Patients AD: An Extended Analysis With Eczema Ointment
 

A poster presented at the recent Fall Clinical Dermatology Conference reported on the results of an extended analysis of crisaborole ointment (Eucrisa), a nonsteroidal phosphodiesterase-4 inhibitor for the treatment of mild to moderate AD. The researchers used the Severity of Pruritus Scale (SPS), a 4-point rating scale, ranging from 0 (none: no itching) to 3 (severe: bothersome itching/scratching which disturbs sleep), which was adapted from the Atopic Dermatitis Severity Index to quantify itch over a 24-hour recall period in the crisaborole phase 3 trials. 

In the prespecified analyses of these trials, pruritus data were analyzed using each SPS observation as a single measure. Subsequent SPS validation analysis determined that averaging at least 2 SPS observations is necessary to provide a reliable measure of pruritus severity, according to the researchers.

For the analysis, data from 2 identically designed, vehicle-controlled, double-blind, phase 3 trials (AD-301 and AD-302) were used. Time to improvement in pruritus (defined as an SPS score ≤1 with a ≥1-point improvement from baseline), proportion of patients experiencing improvement in pruritus by week, pruritus score by week, and proportion of responders by week (clinically important response [CIR] defined by a ≥0.19-point reduction in SPS score from baseline) were analyzed over a 4-week treatment period. A minimum of 2 SPS observations were averaged for each analysis to meet the test and retest reliability threshold of acceptability.

The intent-to-treat population included 759 patients (n=503 in the crisaborole group and n=256 in the vehicle group) for AD-301 and 763 patients (n=513 in the crisaborole group and n=250 in the vehicle group) for AD-302. Using the average of 2 daily SPS observations, crisaborole-treated patients had faster median time to improvement in pruritus than vehicle-treated patients in both trials (AD-301, 5.0 days vs 10.0 days; P<.0003; AD-302, 6.0 days vs 9.0 days; P=.0087). Using the average of all available SPS observations for each week (up to 14 observations), a greater proportion of crisaborole-treated patients showed improvement at week 4 than vehicle-treated patients (week 4: AD-301, 37.2% vs 21.2%; P<.0001; AD-302, 34.4% vs 20.6%; P=.0006); crisaborole-treated patients had lower pruritus scores at each week than vehicle-treated patients (P<.0001, all time points, both trials); and a higher proportion of crisaborole-treated patients were classified as responders per the CIR definition (week 4: AD-301, 74.7% vs 57.1%; P<.0001; AD-302, 71.9% vs 64.2%; P=.0828).

“These extended analyses, based on the validation analysis, show that crisaborole-treated patients experience improvement in pruritus earlier than vehicle-treated patients and that a greater proportion of crisaborole-treated patients experience improvement in pruritus and a clinically important pruritus response,” the researchers concluded. 

Reference

Yosipovitch G, Simpson E, Tan H, et al. The effect of crisaborole ointment, 2%, on pruritus in patients with atopic dermatitis (AD): an extended analysis. Presented at: Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV.

A review of recent news, research, and treatment related to eczema.

Progression From Eczema to Asthma and Allergies 

child itching faceChildren with both atopic dermatitis (AD) and allergic sensitization at age 1 year have a more than 7-fold increased risk for developing asthma as well as an increased risk for developing food allergies by age 3 years, according to a recent study, published in the Journal of Allergy and Clinical Immunology.
 

 The study included 2311 children who underwent skin prick testing at age 1 year and were assessed for AD. Children who produced a 2 mm or larger wheal than that elicited by controls in response to 10 inhalant or food allergens were considered sensitized. At age 3, they were evaluated for asthma, allergic rhinitis, food allergy, and AD.

After adjusting for common confounders, the researchers found that AD without allergic sensitization was not associated with an increased risk of asthma at age 3 years (relative risk [RR], 0.46). However, AD with allergic sensitization was associated with a more than 7-fold increased risk of asthma (RR, 7.04). AD and allergic sensitization had significant interactions on the additive (relative excess risk 5.06) and multiplicative (ratio of RRs 5.80) scales in association with asthma risk. Additionally, there was a positive additive interaction between AD and allergic sensitization in their effects on the risk for developing food allergies (relative excess risk 15.11).

“Atopic dermatitis without concomitant allergic sensitization was not associated with an increased risk of asthma. In combination, atopic dermatitis and allergic sensitization had strong interactive effects on both asthma and food allergy risk at age 3 years,” the researchers concluded. 

 

Reference

Tran MM, Lefebvre DL, Dharma C, et al; Canadian Healthy Infant Longitudinal Development Study investigators. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study [published online November 1, 2017]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2017.08.024

 

depression holding legsAD Increases Depression, Anxiety Among Patients 
 

A recent survey by the National Eczema Association (NEA) found that patients with atopic dermatitis (AD) often report a depression or anxiety diagnosis. The NEA surveyed 545 patients with AD. 

Based on the study, it is estimated that more than 30% of adults with AD are diagnosed with anxiety/depression. The prevalence of AD in adults in the United States is estimated to be 7.2% or 18 million. Adults in the United States with AD say that it impacts almost every area of their lives, including profession, intimate relationships, sleep quality, and overall well-being. 

“Atopic dermatitis is a complex disease as this survey shows,” said Julie Block, president and chief executive officer of NEA. “Research reveals this form of eczema goes well beyond what you see on the skin. Chronic inflammation, symptoms such as unbearable itch, being severely allergic to the world around you—these all profoundly affect the quality of life of people with AD.”

To learn more about eczema and mental health and access resources from the NEA, go to https://nationaleczema.org/eczema-emotional-wellness/. 

Article continues on page 2

{{pagebreak}}

breastfeedingBreastfeeding Intervention May Reduce Eczema Risk in Adolescence

 

A breastfeeding promotion intervention may reduce infants’ risk for flexural eczema during their adolescent years, according to a recent study published online in JAMA Pediatrics.

Atopic diseases such as atopic eczema, asthma, and low lung function are among the most common chronic conditions in children. However, it is not known whether a prolonged breastfeeding intervention influences the risk for these conditions later in life. Carsten Flohr, FRCP, PhD, of King’s College London, and colleagues conducted a follow-up study of the Promotion of Breastfeeding Intervention Trial (PROBIT), which recruited 17,046 healthy term infants from June 16, 1996 to December 31, 1997. Patients were placed in either the intervention group or the control group.

A data analysis was performed from May 9, 2016 to April 21, 2017, and the modified intention-to-treat analysis served as the primary analytic approach. The primary outcomes included spirometry and flexural eczema based on standardized skin examination by study pediatricians, and secondary outcomes included symptoms of flexural eczema within the last year.

Of 17,046 participants, 13,557 (79.5%) were followed up from September 15, 2012 to July 15, 2015. Mean participant age at follow-up was 16.2 years in the intervention group (n=7064) and 16.1 years in the control group (n=6493). Results indicated that 21 (0.3%) patients in the intervention group had flexural eczema upon skin examination compared with 43 (0.7%) patients in the control group.

Findings from the modified intention-to-treat analysis demonstrated that the risk for flexural eczema upon skin examination was 54% lower in the intervention group vs the control group. Furthermore, the rate of self-reported flexural eczema symptoms within the last year was lower in the intervention group vs the control group. However, the researchers noted that 95% CIs were wide and included the null.

All results remained similar following additional adjustment for baseline characteristics, on instrumental variable analysis, and following multiple imputation in all 17,046 participants.

“A breastfeeding promotion intervention reduced flexural dermatitis risk but had no detectable effect on lung function or questionnaire-derived measures of atopic eczema or asthma in adolescence in a setting where atopic eczema and allergies are rare,” the researchers concluded. 

 

Reference

Flohr C, Henderson AJ, Kramer MS, et al. Effect of an intervention to promote breastfeeding on asthma, lung function, and atopic eczema at age 16 years: follow-up of the PROBIT randomized trial [published online November 13, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.4064

 

itchy elbowPruritus in Patients AD: An Extended Analysis With Eczema Ointment
 

A poster presented at the recent Fall Clinical Dermatology Conference reported on the results of an extended analysis of crisaborole ointment (Eucrisa), a nonsteroidal phosphodiesterase-4 inhibitor for the treatment of mild to moderate AD. The researchers used the Severity of Pruritus Scale (SPS), a 4-point rating scale, ranging from 0 (none: no itching) to 3 (severe: bothersome itching/scratching which disturbs sleep), which was adapted from the Atopic Dermatitis Severity Index to quantify itch over a 24-hour recall period in the crisaborole phase 3 trials. 

In the prespecified analyses of these trials, pruritus data were analyzed using each SPS observation as a single measure. Subsequent SPS validation analysis determined that averaging at least 2 SPS observations is necessary to provide a reliable measure of pruritus severity, according to the researchers.

For the analysis, data from 2 identically designed, vehicle-controlled, double-blind, phase 3 trials (AD-301 and AD-302) were used. Time to improvement in pruritus (defined as an SPS score ≤1 with a ≥1-point improvement from baseline), proportion of patients experiencing improvement in pruritus by week, pruritus score by week, and proportion of responders by week (clinically important response [CIR] defined by a ≥0.19-point reduction in SPS score from baseline) were analyzed over a 4-week treatment period. A minimum of 2 SPS observations were averaged for each analysis to meet the test and retest reliability threshold of acceptability.

The intent-to-treat population included 759 patients (n=503 in the crisaborole group and n=256 in the vehicle group) for AD-301 and 763 patients (n=513 in the crisaborole group and n=250 in the vehicle group) for AD-302. Using the average of 2 daily SPS observations, crisaborole-treated patients had faster median time to improvement in pruritus than vehicle-treated patients in both trials (AD-301, 5.0 days vs 10.0 days; P<.0003; AD-302, 6.0 days vs 9.0 days; P=.0087). Using the average of all available SPS observations for each week (up to 14 observations), a greater proportion of crisaborole-treated patients showed improvement at week 4 than vehicle-treated patients (week 4: AD-301, 37.2% vs 21.2%; P<.0001; AD-302, 34.4% vs 20.6%; P=.0006); crisaborole-treated patients had lower pruritus scores at each week than vehicle-treated patients (P<.0001, all time points, both trials); and a higher proportion of crisaborole-treated patients were classified as responders per the CIR definition (week 4: AD-301, 74.7% vs 57.1%; P<.0001; AD-302, 71.9% vs 64.2%; P=.0828).

“These extended analyses, based on the validation analysis, show that crisaborole-treated patients experience improvement in pruritus earlier than vehicle-treated patients and that a greater proportion of crisaborole-treated patients experience improvement in pruritus and a clinically important pruritus response,” the researchers concluded. 

Reference

Yosipovitch G, Simpson E, Tan H, et al. The effect of crisaborole ointment, 2%, on pruritus in patients with atopic dermatitis (AD): an extended analysis. Presented at: Fall Clinical Dermatology Conference; October 12-15, 2017; Las Vegas, NV.