Dermatology

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Are pediatric atopic dermatitis and atopic dermatitis the same disease?

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).

Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

Are pediatric atopic dermatitis and atopic dermatitis the same disease?

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).

Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

Are pediatric atopic dermatitis and atopic dermatitis the same disease?

“Maybe not,” Jonathan I. Silverberg, MD, PhD, MPH, said during the Revolutionizing Atopic Dermatitis symposium.

Dr. Silverberg, director of clinical research in the division of dermatology at George Washington University, Washington, based his comments largely on a review that he and his colleagues carried out to understand how features of atopic dermatitis (AD) vary by region globally as well as by age. They identified 101 studies with sufficient data for meta-analysis and stratified the results by pediatric and adult age groups.

Several signs and symptoms occurred with similar frequency among pediatric and adult patients, including pruritus, xerosis, flexural involvement, extensor involvement, early onset of disease, comorbid atopy, head and neck involvement, and ophthalmic comorbidities. However, adults were found to have more signs of chronic disease, more hand eczema, different patterns of hand eczema, and a stronger relationship of disease activity with emotional factors. Meanwhile, children were found to have more exudative or weeping lesions, more perifollicular eczema, and more pityriasis alba.

Dr. Silverberg showed photos of three adults with varied presentations of extensor involvement, including one “who had a lot of lichenification and thickening of the skin, but over knees where you might think about psoriasis,” he said. “All three of these patients were of Southeast Asian descent. That happens to be a region where this feature was reported much more commonly. It may even tie to some underlying immunopathophysiologic differences of the disease across different patient populations.”

AD signs that occur more commonly in adults than children include lichenification (100% vs. 48%), urticaria (32% vs. 20%), popular lichenoid lesions (46% vs. 8%), Hertoghe’s sign (25% vs. 2%), erythroderma (29% vs. 1%), and nodular prurigo (18% vs. 4%).

Hand eczema features also differ between adults and children, including hand or foot dermatitis (44% vs. 25%), dyshidrosis/pompholyx (21% vs. 3%), knuckle dermatitis (25% vs. 8%), nail involvement (15% vs. 8%), and fissured heels. However, ventral wrist dermatitis was found to be more than twice as common in children, compared with adults (34% vs. 15%).

Other signs of AD were more common in children, compared with adults, including exudative eczema (61% vs. 42%), pityriasis alba (28% vs. 18%), Dennie-Morgan infraorbital folds (47% vs. 36%), seborrheic dermatitis–like lesions (40% vs. 18%), and perifollicular accentuation (37% vs. 21%). “This is such an important sign to wrap your head around and get comfortable assessing,” he said. “I have seen patients who are erythrodermic with follicular eczema who were told that they were crazy and had psychogenic itch, and they should go to a shrink.”

AD triggers can differ between adults and children as well, including course influenced by emotions/environmental factors (72% vs. 32%), worsening itch worse (65% vs. 49%), course influenced by environment (62% vs. 37%), and course influenced by emotions (70% vs. 15%).

According to Dr. Silverberg, emerging research suggests that there may be differences in the immune pathways activated in pediatric versus adult AD. Specifically, more Th17 and interferon-gamma in AD lesions have been observed in children, compared with adults, and more Th22 and Th17 in nonlesional AD have been seen in children, compared with adults. “This leads to a question: Will children respond differently than adults to treatment?” Dr. Silverberg said. “We see that omalizumab doesn’t seem to help much in adults, yet a recent study suggested that it might work reasonably well for children. Dupilumab has different dosing requirements and potentially different responses between the pediatric and adult populations.”

Age differences in AD may also be related to differences in the skin microbiome. In 2016, researchers led by Richard L. Gallo, MD, PhD, professor of dermatology, University of California, San Diego, compared the skin microbiome between adults and children with AD by swabbing the volar forearm and performing 16S rRNA gene sequencing. The study included 59 young children, 13 teenagers, and 56 adults with AD as well as 68 age-matched non-atopic healthy controls. The researchers found a greater abundance of Streptococcus, Granulicatella, Gemella, Rothia, and Haemophilus in young children, compared with adults, while Propionibacterium, Corynebacterium, Staphylococcus, Lactobacillus, Finegoldia, and Anaerococcus were more abundant in adults, compared with children.

Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

[email protected]

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

[email protected]

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

[email protected]

According to Noreen Heer Nicol, PhD, RN, FNP, frustration still exists for patients, families, and health care providers regarding the lack of consensus that routine bathing is good for patients with atopic dermatitis.

monkeybusinessimages/Getty Images

During the Revolutionizing Atopic Dermatitis symposium, she said that conflicting and vague guidelines currently exist on the topic.

“This stems from the fact that we just don’t have good studies,” said Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado at Denver, Aurora. “Particularly, we don’t have randomized, controlled trials on the effects of water and bathing. It’s not just parents that are frustrated, but health care providers are as well.”

In an observational analysis, researchers evaluated results from three online surveys of dermatologists, allergists, and immunologists, and primary care physicians regarding routine bathing frequency recommendations for children with AD. It found that PCPs recommended daily bathing less than 50% of the time, while specialists recommended daily bathing more than 50% of the time.

“It seems like the PCPs have embraced that old dermatology notion when bathing was avoided in patients with AD,” Dr. Nicol said. “This lack of consensus on the basic daily care steps in AD management causes a great deal of confusion amongst patients, families, and young health care providers, in particular,” she added.

She believes that this goes back to a century-long debate about the pros and cons of bathing in AD. “We used to say that bathing will dry the skin out if you take a bath or a shower without immediately applying something like a good moisturizer. That’s where the 3-minute rule came along from the National Eczema Association, meaning that bathing hydrates the stratum corneum if you take a bath or a shower and you immediately apply that good moisturizer within 3 minutes to retain that hydration and keep the barrier intact and flexible.”

Dr. Nicol presented a stepwise management model that she has published many times over the years (see Pediatr Nursing 2020;46[2]:92-8 and J Allergy Clin Immunol Pract 2019;7[1]:1-16).

Step 1 consists of basic care, including skin hydration/bathing, application of a daily moisturizer, avoiding irritants, and identifying and addressing specific triggers. “This is the foundation for every step as you go forward,” she explained. Soak and seal has been a mainstay of treatment at National Jewish Health, she noted. “By that, I mean taking a soaking 10-15 minute bath in warm water daily. Gently pat away excess water. Immediately apply skin medications or moisturizer within 3 minutes. Using a gentle fragrance-free, dye-free cleanser to clean skin is also important. Avoid scrubbing.”

A review article on bathing and associated treatments in AD was published in 2017 and includes 144 references to bathing studies. A separate recommendation known as the “AD Yardstick” published by Dr. Nicol’s colleague at National Jewish Health, Mark Boguniewicz, MD, and coauthors, elaborated on the definition of basic skin care for nonlesional AD. Besides recommending the liberal and frequent application of moisturizers, it suggests management with warm baths or showers using nonsoap cleansers, usually once per day, followed by application of a moisturizer, even on clear areas.

“This is now what people are thinking as the basis of skin care in patients with AD,” Dr. Nicol said. “Warm baths and showers don’t look so controversial anymore. This model nicely lays out what we want people to remember. In the past, many times we just skipped that important step of telling people about bathing.”

In a small 2009 study, researchers conducted a quantitative assessment of combination bathing and moisturizing regimens on skin hydration in AD. They found that bathing followed by application of a moisturizer provides modest hydration benefits, though less than that of simply applying moisturizer alone. “That has not been the case for most of us who are bathing advocates,” Dr. Nicol said. “We believe that there is an additional hydration that’s gained from bathing and moisturizers done properly.”

In an earlier retrospective study of 28 patients referred to a tertiary care center for refractory chronic pruritic eruptions, researchers found that a plain-water 20-minute soak followed by smearing of midstrength corticosteroid ointment led to clearing or dramatic improvement of the lesions (Arch Dermatol 2005;14:1556-9). The authors recommended prospective studies to confirm the findings.

In a separate review of medical literature, researchers explored the role of frequent bathing in the treatment of pediatric AD (Ann Allergy Asthma Immunol 2016;117[1]:9-13). They found that the weight of evidence suggests that the frequent soak and smear bathing is preferred to infrequent bathing in the management of AD. Frequent bathing was defined as bathing at least once a day, while infrequent bathing was defined as bathing less than once a day.

“Bleach baths have received much attention in recent years, and have been endorsed by multiple AD guidelines, though not to the same degree as regular bathing,” Dr. Nicol said. “Right now, you can find almost as much literature for this practice as against it. The populations that seem to value from beach baths the most, however, are those with frequent infections, particularly those who are methicillin resistant. Most people recommend a maximum of two to three times per week but only with an active infection. Care must be taken to avoid additional drying or irritation of the skin from bleach.”

Many bleach bath recipes call for adding one-eighth to one-half of a cup of bleach to a tub full or water.

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

[email protected]

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

[email protected]

Mounting evidence confirms what many clinicians have suspected for years: That daily moisturizers are the bedrock of atopic dermatitis management.

In an updated review of clinical evidence on the topic, Adelaide A. Hebert, MD, Noreen Heer Nicol, PhD, RN, FNP, and colleagues evaluated 13 trials that assessed daily moisturization for the treatment of AD published between 2006 and 2019. “The bottom line is, daily moisturization increased skin hydration and it decreased transepidermal water loss in all children and adults in the 13 studies we looked at,” Dr. Nicol, associate dean and associate professor of nursing at the University of Colorado, Denver, said at the Revolutionizing Atopic Dermatitis symposium.

Based on published evidence in the review, she and her coauthors assembled six points regarding the importance of essential skin repair in AD:

1. It strengthens the barrier that protects against environmental triggers such as skin irritants aeroallergens, dust mites, and pet dander.

2. It decreases moisture loss that perpetuates damage and can provoke inflammatory processes.

3. It promotes a healthy microbiome via induction of antimicrobial peptides.

4. It maintains stratum corneum acidification, which protects against pathogens.

5. It reduces recurrence of flares when used daily.

6. It prevents the onset of AD when applied early in life to at-risk children.

A separate review of optimal AD care authored by Dr. Nicol underscores the importance of foundational management, “meaning that we want you to use hydration and daily moisturizers as part of your everyday management,” she said. “Without good barrier repair, infections and allergens can break through. The intention is to have that barrier repair a key point of moisturizer use.”

In a 2014 published study, researchers investigated the role of proactive emollient therapy in preventing AD in 124 neonates in the United States and the United Kingdom with a first-degree relative with a history of allergic rhinitis, asthma, or AD. The treatment group received daily total body application of Aquaphor Healing Ointment, Cetaphil Cream, or sunflower seed oil, starting at 3 weeks of age, while the control group received no moisturizers. They found that daily emollient therapy significantly reduced the cumulative incidence of AD at 6 months (22% vs. 42% among controls). A follow-up study confirmed a protective but nonsignificant effect of daily moisturizer use at 12 months (AD was diagnosed in 13.2% of those in the treatment group vs. 25% in the control group), most likely due to the study being underpowered.

“The message here is simple,” Dr. Nicol said. “Wouldn’t it be wonderful if we could reduce the burden of AD by doing something as straightforward as moisturizer use in our neonates?”

With so many moisturizers on the market today, considerations include active ingredients, side effects, absorption, and amount required for efficacy. “On the average adult, head to toe, front to back, one time it takes about 30 grams or one ounce of something to cover them completely, so you want to make sure people are using enough,” Dr. Nicol said. “You don’t want to be prescribing people 15- and 30-gram tubes of product and hoping they have enough to cover their bodies multiple times.”

Ten years ago, a randomized, controlled trial found that Aquaphor Healing Ointment was 47 times more cost-effective than prescription barrier creams Atopiclair nonsteroidal cream and EpiCeram controlled release skin barrier emulsion. “The most expensive things do not have to be the best things to be used,” Dr. Nicol said. “Recognize what the properties of these products are and what the benefit is.”

A basic principle of skin care for AD patients recommended by Dr. Nicol and colleagues at National Jewish Health, Denver, includes applying a fragrance-free moisturizer within 3 minutes of finishing a bath or a shower. They recommend products sold in 1-pound jars or large tubes, such as Aquaphor Healing Ointment, Vaniply Ointment, Eucerin Creme (various formulations), Vanicream, CeraVe Cream, or Cetaphil cream. “Vaseline is a good occlusive preparation to seal in but is most effective after bath or shower,” the recommendations continue. “Topical maintenance medications may be used in place of moisturizers or sealer when prescribed.”

She recommends including a list of preferred moisturizers for patients to use into written action plans for skin care. “This adds a lot of benefit to patients,” she said. “Always put the patient at the center of your decision-making. Spend time listening to them, give them options of things that they are willing to use so that they can trust you.”

Dr. Nicol disclosed that she has served as an advisory board member for Eli Lilly & Co.

[email protected]

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

[email protected]

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

[email protected]

In a recent international survey, dermatologists both in the United States and abroad acknowledged major gaps in their competence to provide high-quality care to reproductive-age women with psoriasis, Jenny Murase, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

©monkeybusinessimages/Thinkstock

“In Germany, the UK, and the United States, dermatologists face challenges in discussing pregnancy and child-bearing aspiration with women of reproductive age, in recommending compatible treatments during pregnancy, and engaging patients in the shared decision-making process. These challenges may exist due to suboptimal knowledge, skills, confidence, and attitude in respective areas of care,” said Dr. Murase, a dermatologist at the University of California, San Francisco, and coeditor-in-chief of the International Journal of Women’s Dermatology.

• Forty-seven percent of respondents considered their knowledge of the impact of psoriasis on women’s reproductive health to be suboptimal. This knowledge gap was most common among American dermatologists, 59% of whom rated themselves as having suboptimal knowledge, and least common among German practitioners, only 27% of whom reported deficiencies in this area.

Fifty percent of dermatologists rated themselves as having suboptimal skills in discussing contraceptive methods with their psoriasis patients of childbearing potential.

• Forty-eight percent of respondents – and 59% of the American dermatologists – indicated they prefer to leave pregnancy-related discussions to ob.gyns.
• Fifty-five percent of dermatologists had only limited knowledge of the safety data and indications for prescribing biologic therapies before, during, and after pregnancy. Respondents gave themselves an average score of 58 out of 100 in terms of their confidence in prescribing biologics during pregnancy, compared to 74 out of 100 when prescribing before or after pregnancy.
• Forty-eight percent of participants indicated they had suboptimal skills in helping patients counter obstacles to treatment adherence.

Consideration of treatment of psoriasis in pregnancy requires balancing potential medication risks to the fetus versus the possible maternal and fetal harms of under- or nontreatment of their chronic inflammatory skin disease. It’s a matter that calls for shared decision-making between dermatologist and patient. But the survey showed that shared decision-making was often poorly integrated into clinical practice. Ninety-seven percent of the U.S. dermatologists were unaware of the existence of shared decision-making practice guidelines or models, as were 80% of UK respondents and 85% of the Germans. Of the relatively few dermatologists who were aware of such guidance, nearly half dismissed it as inapplicable to their clinical practice. More than one-third of respondents admitted having suboptimal skills in assessing their patients’ desired level of involvement in medical decisions. And one-third of the German dermatologists and roughly one-quarter of those from the United States and United Kingdom reported feeling pressure to make treatment decisions quickly and without patient input.

Dr. Murase added that the survey findings make a strong case for future interventions designed to help dermatologists appreciate the value of shared decision-making and develop the requisite patient-engagement skills. Dr. Murase reported serving as a paid consultant to UCB Pharma, which funded the survey via an educational grant.

[email protected]

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

A 62-year-old man presented to our skin clinic with multiple pruritic, tense, bullous lesions that manifested on his arms, abdomen, back, and upper thighs over a 1-month period. There were no lesions in his oral cavity or around his eyes, nose, or penile region. He denied dysphagia.

The patient had multiple comorbidities, including diabetes, hypertension, recent stroke, and end-stage renal disease. He was being prepared for dialysis. His medications included torsemide, warfarin, amiodarone, metoprolol, pantoprozole, atorvastatin, and nifedipine. About 3 months prior to this presentation, he was started on oral linaglipton 5 mg/d, an oral antihyperglycemic medication. He had no history of skin disease or cancer, and his family history was not significant.

Physical examination showed multiple 5-mm to 2-cm blisters and bullae on the flexural surface of both of his arms (FIGURE), back, lower abdomen, and upper thighs. His palms and soles were not involved. The lesions were nontender, tense, and filled with clear fluid. Some were intact and others were rupturing. There was no mucocutaneous involvement. Nikolsky sign was negative. There were no signs of bleeding.

The family physician (FP) obtained a 4-mm punch biopsy at the edge of a 6-mm blister for light microscopy and a 3-mm perilesional punch biopsy for direct immunofluorescence (DIF) microscopy.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

DIF of the biopsy sample demonstrated linear deposition of complement 3 (C3) and immunoglobulin (Ig) G along the basement membrane zone. Indirect immunofluorescence on salt-split skin demonstrated linear deposition of IgG and C3 on both the roof and floor of the induced blisters. These findings and the patient’s clinical presentation met the criteria for bullous pemphigoid (BP), which is the most common autoimmune skin-blistering disease.¹

FPs are increasingly using DPP-4 inhibitors as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP

BP is associated with subepidermal blistering, which can occur in reaction to a variety of triggers. Pathogenesis of this condition involves IgG anti-basement membrane autoantibody complex formation with the hemidesmosomal antigens BP230 and BP180—a process that activates C3 and the release of proteases that can be destructive to tissue along the dermo-epidermal junction.¹

Growing incidence. BP usually occurs in patients > 60 years, with no racial or gender preference.¹ The incidence rate of BP ranges from 2.4 to 21.7 new cases per 1 million individuals among various worldwide populations.² The incidence appears to have increased 1.9- to 4.3-fold over the past 2 decades.²

What you’ll see, who’s at risk

Symptoms of BP include localized areas of erythema or pruritic urticarial plaques that gradually become more extensive. A patient may have pruritis alone for an extended period prior to developing blisters and bullae. The bullae are tense and normally 1 to 7 cm in size.¹ Eruption is generalized, mostly affecting the lower abdomen, as well as the flexural parts of the extremities. The palms and soles also can be affected.

FPs should be aware of the atypical clinical variants of BP. In a review by Kridin and Ludwig, variants can be prurigo-like, eczema-like, urticaria-like, dyshidrosiform type, erosive type, and erythema annulare centrifugum–like type.² At-risk populations, such as elderly patients (> 70 years), whose pruritis manifests with or without bullous formation, should be screened for BP.^3,4

Continue to: Risk factors for BP

Risk factors for BP. Certain conditions linked to developing BP include neurologic disorders (dementia and Parkinson disease) and psychiatric disorders (unipolar and bipolar disorder).⁴ Further, it is important to note any medications that could be the cause of a patient’s BP, including dipeptidyl peptidase-4 (DPP-4) inhibitors, psychotropic medications, spironolactone, furosemide, beta-blockers, and antibiotics.³ This patient was taking a beta-blocker (metoprolol) and a DPP-4 inhibitor (linagliptin). Because he was most recently started on linagliptin, we suspected it may have had a causal role in the development of BP.

The association of DPP-4 inhibitors and BP

FPs are increasingly using DPP-4 inhibitors—including sitagliptin, vildagliptin, and linagliptin—as oral antihyperglycemic agents for type 2 diabetes mellitus. Therefore, it’s important to recognize this medication class’s association with BP.⁵ In a case-control study of 165 patients with BP, Benzaquen et al reported that 28 patients who were taking DPP-4 inhibitors had an associated increased risk for BP (adjusted odds ratio = 2.64; 95% confidence interval [CI], 1.19-5.85).³

The pathophysiology of BP associated with DPP-4 inhibitors remains unclear, but mechanisms have been proposed. The DPP-4 enzyme is expressed on many cells, including keratinocytes, T cells, and endothelial cells.³ It is possible that DPP-4 inhibition at these cells could stimulate activity of inflammatory cytokines, which can lead to enhanced local eosinophil activation and trigger bullous formation. DPP-4 enzymes are also involved in forming plasmin, which is a protease that cleaves BP180.³ Inhibition of this process can affect proper cleavage of BP180, impacting its function and antigenicity.^3,6

Other conditions that also exhibit blisters

There are some skin conditions with similar presentations that need to be ruled out in the work-up.

Bullous diabeticorum is a rare, spontaneous, noninflammatory condition found in patients with diabetes.¹ Blisters usually manifest as large, tense, asymmetrical, mildly tender lesions that commonly affect the feet and lower legs but can involve the trunk. These usually develop overnight without preceding trauma. Biopsy would show both intra-­epidermal and subepidermal bulla with normal DIF findings.¹ This condition usually has an excellent prognosis.

Continue to: Pemphigus vulgaris

Pemphigus vulgaris is characterized by nonpruritic, flaccid, painful blisters. This condition usually begins with manifestation of painful oral lesions that evolve into skin blisters. Some patients can develop mucocutaneous lesions.¹ Nikolsky sign is positive in these cases. Light microscopy would show intra-­epidermal bullae.

Dermatitis herpetiformis. This condition—usually affecting middle-age patients—is associated with severe pruritis and burning. It may start with a few pruritic papules or vesicles that later evolve into urticarial papules, vesicles, or bullae. Dermatitis herpetiformis can resemble herpes simplex virus. It can also be associated with gluten-sensitive enteropathy and small bowel lymphoma.¹ DIF of a biopsy sample would show granular deposition of IgA within the tips of the dermal papillae and along the basement membrane of perilesional skin.¹

Epidermolysis bullosa acquisita is a rare, severe, chronic condition with subepidermal mucocutaneous blistering.¹ It is associated with skin fragility and spontaneous trauma-induced blisters that heal with scar formation and milia. IgG autoantibodies reacting to proteins in the basement membrane zone can cause the disease. It is also associated with Crohn disease.¹ DIF findings are similar in BP, but they are differentiated by location of IgG deposits; they can be found on the dermal side of separation in epidermolysis bullosa acquisita, as compared with the epidermal side in BP.¹

How to make the Dx in 3 steps

To effectively diagnose and classify BP, use the following 3-step method:

1. Establish the presence of 3 of 4 ­clinical characteristics: patient’s age > 60 years, absence of atrophic scars, absence of mucosal involvement, and absence of bullous lesions on the head and neck.
2. Order light microscopy. Findings should be consistent with eosinophils and neutrophils containing subepidermal bullae.
3. Order a punch biopsy to obtain a perilesional specimen. DIF of the biopsy findings should feature linear deposits of IgG with or without C3 along the dermo-epidermal junction. This step is essential for an accurate diagnosis.

Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and antiinflammatory antibiotics.

There also is benefit in ordering supplemental studies, such as an enzyme-linked immunosorbent assay for the detection of anti-BP180 or anti-BP230 IgG autoantibodies.⁷ However, for this patient, we did not order this study.

Continue to: Management focuses on steroids

Management focuses on steroids

The offending agent should be discontinued immediately. Depending on the severity of disease, treatment can include the use of potent topical corticosteroids alone or in combination with systemic corticosteroids and anti-inflammatory antibiotics (eg, doxycycline, minocycline, erythromycin).^1,7 For patients with resistant or refractory disease, consider azathioprine, methotrexate, dapsone, and chlorambucil.^1,7 Exceptional cases may benefit from the use of mycophenolate mofetil, intravenous immunoglobulin, or plasmapheresis.^1,7

For this patient, initial treatment included discontinuation of linagliption and introduction of topical clobetasol 0.05% and oral prednisone 40 mg/d for 7 days, followed by prednisone 20 mg for 7 days. He was also started on oral doxycycline 100 mg bid and oral nicotinamide 500 mg bid.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.

Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that is well known for its relapsing, pruritic rash in children and adults. Less recognized are its associated conditions—allergic rhinitis, asthma, food allergies, attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety—and its burden on patients and their families. In fact, families that have children with AD report lower overall quality of life than those with otherwise healthy children.¹ Given AD’s prevalence across age groups and its effect on the family, family physicians are uniquely positioned to diagnose, care for, and counsel patients with AD and its associated maladies.

The prevalence and pathogenesis of AD

AD affects up to 20% of children and 5% of adults in the United States.² AD typically manifests before a child reaches age 5 (often in the first 6 months of life), and it is slightly more common in females (1.3:1). A family history of atopy (eczema, asthma, allergic rhinitis) is common. In fact, children with one atopic parent have a 2- to 3-fold increased risk of atopic dermatitis; those with 2 atopic parents have a 3- to 5-fold increased risk.³

The pathophysiology of AD is complex, culminating in impaired barrier function of the skin and transepidermal water loss resulting in dry and inflamed skin. Additionally, alterations in a cell-mediated immune response leading to an immunoglobulin (Ig) E-mediated hypersensitivity is also theorized to play a role in the development of AD.

Signs and symptoms

Signs at birth. Physical signs of atopic dermatitis typically appear between birth and 6 months. In infancy, lesions generally occur on the scalp, face (FIGURES 1A and 1B), neck, and extensor surfaces of the extremities. Lesions are typically papules and vesicles, sometimes accompanied by serous exudate and crusting. Eczematous lesions typically spare the groin and diaper area, and their presence in this area should raise suspicion for an alternative diagnosis.

Beginning at age 2 years, eczematous lesions are more commonly limited to the folds of the flexor surfaces. Instead of the weeping and crusting lesions seen in infancy, eczema in older children manifests as dry, lichenified papules and plaques in areas that are typically affected in adults: the wrist, hands, ankles, and popliteal and antecubital fossa.²

Although lesions in adults are similar to those of childhood, they may manifest in a more localized area (hand or eyelid, for example). As is the case in childhood, the lesions are dry, sometimes lichenified, and found on the flexural surfaces (FIGURES 2A and 2B).²

Symptom triggers are unproven

While anecdotal reports cite various triggers for AD flares, a systematic review found little scientific evidence to substantiate identifiable triggers.⁴ Triggers often cited and studied are foods, dust mite exposure, airborne allergens, detergents, sunlight, fabrics, bacterial infections, and stress. While as many as one-third of people with AD who also have confirmed dust mite allergy report worsening of symptoms when exposed to dust, a Cochrane review of 7 randomized controlled trials totaling 324 adults and children with eczema found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms.⁵

Continue to: How quality of life diminishes with AD

How quality of life diminishes with AD

AD substantially lessens quality of life. For children, the most distressing physical symptoms include itching that inhibits sleep and provokes scratching, pain, and bleeding. Emotional distress can cause irritability, crying, and uncooperativeness with treatments. Parents also report that they frequently restrict their children from activities, such as playing in the heat or swimming, that may lead to worsening of their eczema.⁶

The loss of sleep associated with AD is not completely understood but is likely multifactorial. Pruritus and scratching leading to sleeplessness is the most obvious culprit, but an altered circadian rhythm, immune system response, and changes in skin physiology are also likely factors.⁷ Whatever the cause, sleep disturbance is reported in as many as 60% of patients with AD, and the degree of sleep disturbance is proportional to increases in disease severity and worsening of quality-of-life scores.⁸ Lost sleep is not limited to patients; parents of children with AD also report significant loss of sleep and subsequent decreased work productivity and quality of life.⁹

Children with AD are often the target of bullying.¹⁰ A 2015 survey by the National Eczema Association indicates that 1 in 5 children reported being bullied due to their AD.¹¹

Associated conditions and comorbidities

AD increases patients’ risks for other illnesses, due either to their underlying atopy or to the effects of AD symptoms (TABLE^12-17).

Atopic march

Atopic march—the clinical succession of AD, allergic rhinitis, and asthma—is a well-­established clinical progression. The presence of all 3 conditions appears to be more common in children diagnosed with AD before 2 years of age.¹² Typically, allergic rhinitis manifests at around age 4, and asthma develops between ages 6 and 8. The severity of AD predicts progression. Compared with an 8% chance of asthma developing among the general population, children with mild AD have a 20% to 30% chance of developing asthma, and those with severe AD have about a 70% chance.¹²

Continue to: Food allergies

Patients with AD are at higher risk for food-induced anaphylaxis, with up to one-third of AD patients having an IgE-mediated food allergy.¹³ While it is theorized that the impaired skin barrier of an atopic child may allow for early sensitization and allergy development, a landmark 2015 study demonstrated that early allergen introduction (specifically, peanuts) may serve as a preventive strategy in those at high risk of food allergies.¹⁴ Current guidelines recommend that physicians be aware of the increased possibility of food allergies in those with AD, and consider evaluating a child for milk, egg, peanut, wheat, and soy allergy if the child is younger than 5 years and has eczema that does not resolve with treatment, or has eczema and a history of an allergic reaction to a specific food.¹⁵

Interestingly, despite the strong association between AD and food allergies, it is not clear that food allergies trigger atopic flares; as such, elimination diets are not universally recommended in those without a proven food allergy.

Psychiatric diagnoses

Children with AD have an increased prevalence of several psychiatric conditions, including ADHD, depression, anxiety, conduct disorder, and autism when compared with peers who do not have AD, and the probability correlates with the severity of AD.¹⁶ While there is a clear link—secondary to nocturnal pruritis—between AD and sleep deprivation, it is not clear whether the sleep deprivation leads to an increase in these psychiatric conditions or if AD is an independent risk factor.

Consider recommending bleach baths in cases of moderate-to-severe atopic dermatitis with frequent bacterial infections.

What we do know is that one of the strongest associations between AD and a psychiatric condition is with ADHD, with a recent pooled meta-analysis showing a 46% increase in risk.¹⁷ The incidence of depression among children with AD appears to correlate with the severity of AD symptoms: estimated at 5% with mild AD, 7% with moderate disease, and 14% with severe disease (compared with 3% without AD). Similar incremental increases are seen when correlating AD and anxiety.¹⁶

Nonpharmacologic care

Bathing

Bathing habits are critical to controlling AD. While bathing serves to both hydrate the skin and remove allergens, the water’s evaporation off the skin surface can lead to increased transepidermal water loss. Combining bathing and immediate application of a moisturizer improves skin hydration in patients with AD vs bathing alone.¹⁸ Thus, consensus guidelines recommend once-daily bathing (bath or shower) to remove scale and crust, followed by immediate application of a moisturizing emollient.¹⁹

Continue to: Emollients

Application of moisturizing emollients is the mainstay of nonpharmacologic care of AD, and there is strong evidence that their regimented use reduces disease burden and the need for prescription treatment.¹⁹ Emollient creams and ointments help retain moisture and improve the skin’s barrier. While ointments may provide a better barrier, patients tend to prefer creams as they are less greasy than ointments.

Emollient therapy may also help prevent development of AD, especially in those infants thought to be at high risk with a family history of atopy. In a multinational randomized controlled trial, infants who received daily full-body application of emollient beginning at 3 weeks of life were significantly less likely than controls to develop AD by 6 months.²⁰ While the mechanism of action is not clearly understood, it is believed that early emollient use prevents skin dehydration and maintains the skin’s barrier integrity, thus decreasing allergen epidermal penetration and subsequent inflammation.

Bleach bath

A bleach bath, prepared by adding 1/2 cup of unconcentrated bleach (5.25% sodium hypochlorite) to a standard 40-gallon bathtub, produces a chlorine mixture equivalent to an average swimming pool. Soaking in a bleach bath for 10 minutes once or twice weekly is thought to reduce inflammation and bacteria on the skin, but studies of its efficacy in improving atopic symptoms are mixed.

In a pooled analysis of 5 studies evaluating bleach baths vs standard baths, there was no significant difference in disease severity at 4 weeks.²¹ Thus, while bleach baths were effective in decreasing disease severity, they appeared to be no more effective than a standard water bath.²¹ Bleach baths may be helpful, however, in cases of moderate-to-severe disease with frequent bacterial infections.¹⁹

Pharmacologic therapy

Steroids

For symptoms refractory to nonpharmacologic skin care, topical steroids are the initial pharmacologic treatment for AD.19 Choose steroid potency based on symptom severity and disease location. Low- to medium-potency is appropriate for mild disease, and medium- to high-potency is useful for ­moderate-to-severe symptoms. High-­potency steroids are generally avoided on the face and skin folds; however, they can be used for short periods in these areas to induce remission. They must then be quickly tapered and discontinued.

Continue to: Frequency

Frequency. Topical corticosteroids are typically applied twice daily, although recent studies indicate that once-daily application is just as efficacious.²² In addition to treatment of an acute flare, topical steroids are useful as maintenance therapy for patients with recurrent outbreaks in the same anatomical site. Guidelines suggest once- or twice-weekly application of a medium-potency steroid to prolong time between flares.¹⁹

For children, a practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.²³ Topical steroids are generally well tolerated and have a good safety profile. Adverse effects are proportional to the amount and duration of use and include purpura, telangiectasias, striae, and skin atrophy. The risk of skin atrophy increases with higher potency steroids, occlusion (covering affected area after steroid application), use on thin-skinned areas, and older patient age.²⁴

A Cochrane review found that efforts at dust mite mitigation (laundering of bed covers, increased vacuuming, spraying for mites) were not effective in reducing symptoms of atopic dermatitis.

Reassure patients/parents about the safety of topical steroids, as fears regarding the potential adverse effects can limit compliance. In one study of 200 patients with AD, 72.5% of respondents expressed fear of using steroids on their own skin or that of their child, and 24% admitted being noncompliant with therapy based on these concerns.²⁵

Treating flares. Oral steroids are sometimes needed to abort or control an AD flare in older children and adults. A tapering course of prednisone over 5 to 7 days, transitioning to medium- to high-dose topical steroids, may be needed to achieve symptom control.

Topical calcineurin inhibitors

Topical calcineurin inhibitors, including tacrolimus and pimecrolimus, are generally second-line therapy to topical corticosteroids. However, as nonsteroidal agents, topical calcineurin inhibitors do not cause skin atrophy and can be a first-line option in areas where atrophy is more common (face, eyelids, neck, and skin folds).²⁶

Continue to: A Cochrane review found...

Interestingly, despite the strong association between atopic dermatitis and food allergies, it is not clear that food allergies trigger atopic flares.

A Cochrane review found tacrolimus 0.1% to be better than low‐potency topical corticosteroids on the face and neck areas, while results were equivocal when compared with moderate‐potency topical corticosteroids on the trunk and extremities (no difference based on physician assessment, but marginal benefit favoring tacrolimus based on participant scoring).²⁷ When compared head-to-head, tacrolimus was more effective than pimecrolimus, although tacrolimus has a higher rate of local irritation. The most common adverse effects are stinging and burning at the application site, although these adverse effects generally improve with repeated application.

There have been long-term safety concerns with topical calcineurin inhibitors—chiefly a 2006 Food and Drug Administration (FDA) black box warning regarding a possible link between topical calcineurin inhibitors and cancer. However, while there may be a slight increased risk of lymphoma in AD patients, a recent meta-analysis did not find an association between topical calcineurin inhibitors use and lymphoma.²⁸ Given the initial concern—and pending additional data—the FDA currently recommends reserving topical calcineurin inhibitors for second-line therapy and only for the minimum amount of time to induce improvement. It also recommends avoiding their use in patients younger than 2 years and in those with compromised immune systems.

Cisaborole

Cisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor, received FDA approval in 2016 for mild-to-moderate AD. By inhibiting PDE4, the drug limits inflammation. In a multicenter randomized trial, patients applying cisaborole 2% twice a day noted reductions in pruritus, inflammation, excoriation, and lichenification.²⁹ Adverse effects are minimal and limited to application site irritation.

Systemic treatments

While beyond the care of a family physician, symptoms refractory to conservative, nonpharmacologic measures and combinations of topical pharmaceuticals can be treated with systemic immunomodulators such as cyclosporine, azathioprine, and methotrexate. Phototherapy is also effective in patients with more widespread skin involvement. Dupilumab, an injectable monoclonal antibody that binds to interleukin-4 receptor and inhibits inflammation, is approved to treat moderate-to-severe AD in adults.³⁰

Ineffective therapies: Oral montelukast and probiotics

While oral antihistamines are frequently prescribed and used, there are no studies evaluating the use of antihistamines (H1) as monotherapy for AD.³¹ Nonetheless, while not altering the disease process, the sedative effect of antihistamines may palliate the nocturnal pruritus frequently associated with AD. Although nonsedating antihistamines may still have a role for atopic patients with concurrent seasonal and environmental allergies, there is no evidence to support their use in the treatment of AD.

Continue to: Data are limited...

Data are limited on the effectiveness of leukotriene receptor antagonists for AD, and all studies meeting inclusion for a Cochrane review assessed oral montelukast. The review found no benefit with the use of montelukast 10 mg in terms of severity of disease, pruritus, or need for topical steroids.³²

A practical guide is for caregivers to apply the amount of steroid covering 1 adult fingertip to an area of the child’s skin equal to that of 2 adult palms.

A systematic review investigating the benefit of probiotics for the treatment of AD found no improvement in patient-rated eczema scores for quality of life.³³ Additionally, a review of 11 randomized controlled trials including 596 participants found no evidence to suggest efficacy of fish oil, zinc, selenium, vitamin D, vitamin E, pyridoxine, sea buckthorn oil, hempseed oil, or sunflower oil in the treatment of AD.³⁴

Education can reduce AD severity

Family physicians can be a source of education and support for patients and families of patients with AD. Support programs for adults with AD—including education, relaxation techniques, and cognitive behavioral therapy—have been shown to decrease disease severity.³⁵ Comparable improvement in disease severity has been demonstrated in children with AD when similar education is provided to them and their families.

CORRESPONDENCE
Franklin Berkey, DO, Penn State Health, 1850 East Park Avenue, Suite 207, State College, PA 16803; fberkey@ pennstatehealth.psu.edu.