Atopic Dermatitis

A long-term safety study of crisaborole showed few safety concerns, suggesting that the therapy has the potential to treat atopic dermatitis without the side effects of the current topical treatments, said Lawrence F. Eichenfield, MD, of Rady Children’s Hospital, San Diego, and his associates.

The multicenter, long-term, open-label safety study of 48 weeks assessed 517 patients with mild to moderate atopic dermatitis after they had finished a 28-day phase 3 study of 2% crisaborole ointment. The patients in the extension study were told to apply crisaborole twice daily for 28 days, with an off-treatment period initiated if their disease severity was clear or almost clear after the 28 days. They were told to stop the treatment if they had no improvement in their Investigator’s Static Global Assessment score after three consecutive treatment periods.

aniaostudio/Thinkstock

dermnews@frontlinemedcom.com

A long-term safety study of crisaborole showed few safety concerns, suggesting that the therapy has the potential to treat atopic dermatitis without the side effects of the current topical treatments, said Lawrence F. Eichenfield, MD, of Rady Children’s Hospital, San Diego, and his associates.

The multicenter, long-term, open-label safety study of 48 weeks assessed 517 patients with mild to moderate atopic dermatitis after they had finished a 28-day phase 3 study of 2% crisaborole ointment. The patients in the extension study were told to apply crisaborole twice daily for 28 days, with an off-treatment period initiated if their disease severity was clear or almost clear after the 28 days. They were told to stop the treatment if they had no improvement in their Investigator’s Static Global Assessment score after three consecutive treatment periods.

aniaostudio/Thinkstock

dermnews@frontlinemedcom.com

A long-term safety study of crisaborole showed few safety concerns, suggesting that the therapy has the potential to treat atopic dermatitis without the side effects of the current topical treatments, said Lawrence F. Eichenfield, MD, of Rady Children’s Hospital, San Diego, and his associates.

The multicenter, long-term, open-label safety study of 48 weeks assessed 517 patients with mild to moderate atopic dermatitis after they had finished a 28-day phase 3 study of 2% crisaborole ointment. The patients in the extension study were told to apply crisaborole twice daily for 28 days, with an off-treatment period initiated if their disease severity was clear or almost clear after the 28 days. They were told to stop the treatment if they had no improvement in their Investigator’s Static Global Assessment score after three consecutive treatment periods.

aniaostudio/Thinkstock

dermnews@frontlinemedcom.com

Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.

In these older AD patients, long-term treatment with systemic therapy frequently is used to prevent flare-ups and improve patient quality of life. Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
 

Older systemic medications

These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.

Newer drug options

One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.

The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.

The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.

The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.

Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.

Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.

In these older AD patients, long-term treatment with systemic therapy frequently is used to prevent flare-ups and improve patient quality of life. Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
 

Older systemic medications

These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.

Newer drug options

One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.

The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.

The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.

The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.

Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.

Atopic dermatitis (AD) that becomes chronic and persists into adulthood often becomes less responsive to topical treatment with mid- to high-potency corticosteroids and calcineurin inhibitors, necessitating a different approach.

In these older AD patients, long-term treatment with systemic therapy frequently is used to prevent flare-ups and improve patient quality of life. Joseph F. Fowler Jr., MD, discussed these treatment options at the annual Coastal Dermatology Symposium.
 

Older systemic medications

These include methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, and retinoids. Methotrexate is predictably effective, and dermatologists generally are comfortable with it. The drug requires monitoring for adverse effects along with other precautions, similar to its use in psoriasis.

Newer drug options

One is dupilumab (Dupixent), an antibody that blocks interleukin (IL)–4 and IL-13. It received Food and Drug Administration approval in March 2017 for moderate to severe atopic dermatitis that doesn’t respond to topical treatment. Most patients get at least some benefit from the injectable drug, and some get a strong benefit, according to Dr. Fowler, although he pointed out that it can take 12 weeks before it achieves maximum effect. The initial dose is 600 mg administered subcutaneously, followed by 300 mg every 2 weeks. At 16 weeks, it reduced Eczema Area and Severity Index (EASI) scores by about 75% in patients taking a 300 mg dose every other week, compared with about a 20% decline in placebo.

The IL12/23 inhibitor ustekinumab (Stelara), approved for psoriasis and psoriatic arthritis, was effective in a case series of three patients. It led to a greater than 50% reduction in EASI score at week 16, following doses with 45 mg at weeks 0, 4, and 12. Biopsies revealed reductions in Th22 cells and cytokine levels. But, as a caveat, Dr. Fowler reported personal communication with two eczema experts who said they had seen little or no effect with ustekinumab in 10 patients.

The Janus kinase inhibitor tofacitinib, approved for rheumatoid arthritis, also is under investigation for AD. A trial in six patients who had not achieved adequate control with methotrexate or azathioprine showed a 67% improvement in the SCORAD (Scoring Atopic Dermatitis) index at doses of 5 mg of tofacitinib twice per day in five patients and 5 mg every other day in one patient, he said.

The PDE-4 inhibitor apremilast, approved for psoriasis and psoriatic arthritis, has been reported to improve AD symptoms in individual patients. Celgene demonstrated some improvement in a clinical trial of apremilast at doses of 30 or 40 mg twice per day, but the company isn’t pursuing AD as an indication, he noted.

Dr. Fowler has consulted for Abbvie, IntraDerm, and SmartPractice. He is on the speaker’s bureaus of SmartPractice and Regeneron/Sanofi. He has been a research investigator for Abbvie, Allergan, Amgen, Bayer, Dow, Galderma, Genentech, InnovaDerm, Johnson & Johnson, Lilly, Merck, Novartis, Pfizer, Precision Dermatology, Regeneron, SmartPractice, Taro, and Valeant. This publication and the Global Academy for Medical Education are owned by Frontline Medical News.

NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.

That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.

“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.

Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.

The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.

Learning from the mighty mite

For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.

Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.

Eriklam/Thinkstock

Atopic dermatitis

Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.

In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.

In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.

A rash of itches

Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.

‘The perfect culture plate’

Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.

Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”

But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.

A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.

Monoclonal antibody targets IL-31

The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.

But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.

Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.

Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.

NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.

That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.

“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.

Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.

The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.

Learning from the mighty mite

For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.

Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.

Eriklam/Thinkstock

Atopic dermatitis

Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.

In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.

In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.

A rash of itches

Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.

‘The perfect culture plate’

Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.

Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”

But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.

A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.

Monoclonal antibody targets IL-31

The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.

But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.

Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.

Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.

NEW YORK – We share more than affection with our dogs and cats. We also share diseases – about which our four-legged furry friends can teach us plenty.

That was the conclusion of speakers at a session on “cases at the intersection of human and veterinary dermatology,” presented at the summer meeting of the American Academy of Dermatology.

“Human health is intimately connected to animal health,” said Jennifer Gardner, MD, of the division of dermatology, University of Washington, Seattle, and a collaborating member of the school’s Center for One Health Research. The One Health framework looks at factors involved in the human, environmental, and animal sectors from the molecular level to the individual level and even to the planetary level.

Dr. Gardner challenged her audience to think beyond their individual areas of expertise. “How does the work you’re doing with a patient or test tube connect up the line and make an impact to levels higher up?” she asked.

The One Health framework also challenges practitioners to look horizontally, at how work done in the human world connects to what’s going on in the veterinary world – that is, how treatments for dermatologic conditions in dogs may one day affect how dermatologists treat the same or similar disorders in humans.

Learning from the mighty mite

For example, the study of mites that live on the skin of animals could eventually shed light on how dermatologists treat mite-related conditions in humans.

Dirk M. Elston, MD, professor and chair of the department of dermatology at the Medical University of South Carolina, Charleston, noted that Demodex mites occur in humans and in pets.

Eriklam/Thinkstock

Atopic dermatitis

Atopic dermatitis (AD) tends to be similar in people and dogs, according to Charles W. Bradley, DVM, of the University of Pennsylvania School of Veterinary Medicine, Philadelphia. About 10%-30% of children and up to 10% of adults have the disorder, the prevalence of which has more than doubled in recent years, he said.

In dogs, the prevalence is 10%-20%, making it “an extraordinarily common disorder,” he said. Lesions tend to be located on the feet, face, pinnae, ventrum, and axilla/inguinum. Additional sites vary by breed, with Dalmatians tending to get AD on the lips, French Bulldogs on the eyelids, German Shepherds on the elbows, Shar-Peis on the thorax, and Boxers on the ears.

In humans, Staphylococcus aureus is the chief microorganism of concern, said Elizabeth Grice, PhD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who copresented the topic with Dr. Bradley.

A rash of itches

Among dermatology patients – man or beast – itch can outweigh rash as a key focus of concern, according to Brian Kim, MD, of the division of dermatology at Washington University in St. Louis, and codirector for the University’s Center for the Study of Itch. “The problem is my patients don’t complain about their rash; they complain about their itch,” he said. “But we don’t understand the basic question of itch.” In fact, the FDA has not approved any drugs for the treatment of chronic itch, he said.

‘The perfect culture plate’

Lessons can be learned from studying canine AD, which “is immunophysiologically homologous to human AD,” said Daniel O. Morris, DVM, MPH, professor of dermatology, at the University of Pennsylvania School of Veterinary Medicine, Philadelphia. “The main difference: My patients are covered in dense hair coats.” Because of that, systemic treatment is necessary, he said.

Canine AD primarily affects areas where hair is sparse or where the surface microclimate is moist, he said. A dog’s ear canal, which can be 10 times longer than a human’s, harbors plenty of moisture and heat, he said. “It’s the perfect culture plate.”

But, he added, the owners of his patients tend to resist using topical therapies “that could be potentially smeared on the babies and grandma’s diabetic foot ulcer.” So he has long relied on systemic treatments, initially steroids and cyclosporine. But they can have major side effects, and cyclosporine can take 60-90 days before it exerts maximum effect.

A faster-acting compound called oclacitinib has shown promise based on its high affinity for inhibiting JAK-1 enzyme-mediated activation of cytokine expression, including interleukin (IL)-31, he said. “Clinical trials demonstrate an antipruritic efficacy equivalent to both prednisolone and cyclosporine,” he noted. Contraindications include a history of neoplasia, the presence of severe infection, and age under 1 year.

Monoclonal antibody targets IL-31

The latest promising arrival is lokivetmab, a monoclonal antibody that targets canine IL-31, according to Dr. Morris. It acts rapidly (within 1 day for many dogs) and prevents binding of IL-31 to its neuronal receptor for at least a month, thereby interrupting neurotransmission of itch.

But side effects can be serious and common. Equal efficacy with a reduced side effect is the holy grail, he said.

Some doctors are not waiting. “People are throwing these two products at anything that itches,” he said. Unfortunately, they tend to “work miserably” for causes other than AD, he added.

Dr. Gardner, Dr. Elston, Dr. Rook, Dr. Bradley, and Dr. Morris reported no financial conflicts. Dr. Grice’s disclosures include having served as a speaker for GlaxoSmithKline and for L’Oreal France, and having received grants/research funding from Janssen Research & Development. Dr. Kim has served as a consultant to biotechnology and pharmaceutical companies.

GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com


 

GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com


 

GENEVA – The novel interleukin-4 and IL-13 signaling blocker dupilumab displayed consistently strong efficacy across all patient subgroups in a new analysis from the landmark 52-week CHRONOS trial, Andrew Blauvelt, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

“Dupilumab with concomitant topical corticosteroids improved signs and symptoms of atopic dermatitis, compared with placebo injections regardless of age, sex, BMI, or prior history of asthma, allergic rhinitis, or food allergies,” he said. Indeed, he quipped that the biologic proved to be “boring” in its broad effectiveness.

Bruce Jancin/Frontline Medical News

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com


 

Atopic dermatitis (AD) is a vexing multisystem disorder characterized by frequently recurrent, intrusive, and sometimes disabling itch and dermatitis. The itch may be present throughout the day but crescendos at bedtime or 1 to 2 hours after sleep initiation, resulting in disrupted sleep cycles, lack of rest, more hours scratching, daytime somnolence, poor work attendance and performance, and poor school attendance and performance.¹

Atopic dermatitis is a lifelong disease that only remits in approximately half of patients.² There is a need for a disease-specific systemic drug in AD. Phototherapy, cyclosporine, methotrexate, and azathioprine are nonspecific immunosuppressive agents that can be used off label for AD but may or may not be effective.³ Oral or intramuscular corticosteroids are associated with problematic side effects such as weight gain, osteoporosis, fractures, psychological problems, striae, buffalo hump, and steroid withdrawal symptoms and disease aggravation upon withdrawal (ie, flaring to a state worse than prior to steroid initiation).^3,4

A biologic medication for AD has been long overdue. Psoriatic biologic medications have been tried in AD with occasional benefit in case reports but no major response in larger trials. Belloni et al⁵ reviewed early data on off-label usage of biologics approved by the US Food and Drug Administration for psoriasis or other indications applied to AD patients. In their review of cases, they make the point that results are variable and anti-B-cell activity may hold the greatest promise.⁵ On the other hand, a recent series of 3 patients showed limited response to rituximab in chronic AD,⁶ while a combination of omalizumab, an anti-IgE medication, and rituximab was helpful in some patients.⁷ Ultimately, the issue is that nonspecific biologics may or may not address the underlying disease factors in AD. Therefore, there has been a true need for biologic intervention targeted directly at the pathogenic mechanism of AD. Furthermore, the desire for a biologic targeted at AD is paired with the true need to have a medication so targeted that the drug would have little effect on the rest of the immune system, resulting in targeted immunomodulation without secondary risk of infections.

Wait no longer, that era arrived a few months ago with the rapid US Food and Drug Administration approval of dupilumab, an injectable medication used every 2 weeks for the therapy of moderate to severe AD. This fully human monoclonal antibody against the IL-4Rα subunit blocks IL-4 and IL-13, key inflammatory agents in the triggering of production of IgE and eosinophil activation. Even better than the fact that it is targeted are the excellent outcomes in the therapy of moderate to severe AD in adults and the minimal side-effect profile resulting in no requirements for laboratory screening or ongoing monitoring.⁸

Dupilumab seems to perform well, both clinically and in improving the lives of AD patients. Meta-analysis of trials involving dupilumab has shown improved health-related quality of life outcomes.^9,10 Usage of dupilumab alone in clinical trials for 16 weeks (SOLO 1 and SOLO 2) has resulted in stunning reduction in disease severity with a limited side-effect profile, with patients most commonly reporting conjunctivitis.¹¹ In real-world models where dupilumab is added into a regimen of topical corticosteroid usage (LIBERTY AD CHRONOS trial), patients fared even better with the combination, highlighting that this medication may best be used adjunctively to our skin care guidance as dermatologists.¹²

A new era for AD patients has arrived and we as practitioners are now fortunate to be able to therapeutically reach the worst cases of AD. The new era has only begun with dozens of new agents addressing a variety of interleukin pathways including IL-17 and IL-22 still under development. Ultimately, we hope that ongoing pediatric trials will allow us to glean the role of early disease intervention at the root cause of AD and address our abilities to prevent comorbidities and disease persistence. Will we be able to avert years of disabling disease? The future holds immense hope.

Atopic dermatitis (AD) is a vexing multisystem disorder characterized by frequently recurrent, intrusive, and sometimes disabling itch and dermatitis. The itch may be present throughout the day but crescendos at bedtime or 1 to 2 hours after sleep initiation, resulting in disrupted sleep cycles, lack of rest, more hours scratching, daytime somnolence, poor work attendance and performance, and poor school attendance and performance.¹

Atopic dermatitis is a lifelong disease that only remits in approximately half of patients.² There is a need for a disease-specific systemic drug in AD. Phototherapy, cyclosporine, methotrexate, and azathioprine are nonspecific immunosuppressive agents that can be used off label for AD but may or may not be effective.³ Oral or intramuscular corticosteroids are associated with problematic side effects such as weight gain, osteoporosis, fractures, psychological problems, striae, buffalo hump, and steroid withdrawal symptoms and disease aggravation upon withdrawal (ie, flaring to a state worse than prior to steroid initiation).^3,4

A biologic medication for AD has been long overdue. Psoriatic biologic medications have been tried in AD with occasional benefit in case reports but no major response in larger trials. Belloni et al⁵ reviewed early data on off-label usage of biologics approved by the US Food and Drug Administration for psoriasis or other indications applied to AD patients. In their review of cases, they make the point that results are variable and anti-B-cell activity may hold the greatest promise.⁵ On the other hand, a recent series of 3 patients showed limited response to rituximab in chronic AD,⁶ while a combination of omalizumab, an anti-IgE medication, and rituximab was helpful in some patients.⁷ Ultimately, the issue is that nonspecific biologics may or may not address the underlying disease factors in AD. Therefore, there has been a true need for biologic intervention targeted directly at the pathogenic mechanism of AD. Furthermore, the desire for a biologic targeted at AD is paired with the true need to have a medication so targeted that the drug would have little effect on the rest of the immune system, resulting in targeted immunomodulation without secondary risk of infections.

Wait no longer, that era arrived a few months ago with the rapid US Food and Drug Administration approval of dupilumab, an injectable medication used every 2 weeks for the therapy of moderate to severe AD. This fully human monoclonal antibody against the IL-4Rα subunit blocks IL-4 and IL-13, key inflammatory agents in the triggering of production of IgE and eosinophil activation. Even better than the fact that it is targeted are the excellent outcomes in the therapy of moderate to severe AD in adults and the minimal side-effect profile resulting in no requirements for laboratory screening or ongoing monitoring.⁸

Dupilumab seems to perform well, both clinically and in improving the lives of AD patients. Meta-analysis of trials involving dupilumab has shown improved health-related quality of life outcomes.^9,10 Usage of dupilumab alone in clinical trials for 16 weeks (SOLO 1 and SOLO 2) has resulted in stunning reduction in disease severity with a limited side-effect profile, with patients most commonly reporting conjunctivitis.¹¹ In real-world models where dupilumab is added into a regimen of topical corticosteroid usage (LIBERTY AD CHRONOS trial), patients fared even better with the combination, highlighting that this medication may best be used adjunctively to our skin care guidance as dermatologists.¹²

A new era for AD patients has arrived and we as practitioners are now fortunate to be able to therapeutically reach the worst cases of AD. The new era has only begun with dozens of new agents addressing a variety of interleukin pathways including IL-17 and IL-22 still under development. Ultimately, we hope that ongoing pediatric trials will allow us to glean the role of early disease intervention at the root cause of AD and address our abilities to prevent comorbidities and disease persistence. Will we be able to avert years of disabling disease? The future holds immense hope.

Atopic dermatitis (AD) is a vexing multisystem disorder characterized by frequently recurrent, intrusive, and sometimes disabling itch and dermatitis. The itch may be present throughout the day but crescendos at bedtime or 1 to 2 hours after sleep initiation, resulting in disrupted sleep cycles, lack of rest, more hours scratching, daytime somnolence, poor work attendance and performance, and poor school attendance and performance.¹

Atopic dermatitis is a lifelong disease that only remits in approximately half of patients.² There is a need for a disease-specific systemic drug in AD. Phototherapy, cyclosporine, methotrexate, and azathioprine are nonspecific immunosuppressive agents that can be used off label for AD but may or may not be effective.³ Oral or intramuscular corticosteroids are associated with problematic side effects such as weight gain, osteoporosis, fractures, psychological problems, striae, buffalo hump, and steroid withdrawal symptoms and disease aggravation upon withdrawal (ie, flaring to a state worse than prior to steroid initiation).^3,4

A biologic medication for AD has been long overdue. Psoriatic biologic medications have been tried in AD with occasional benefit in case reports but no major response in larger trials. Belloni et al⁵ reviewed early data on off-label usage of biologics approved by the US Food and Drug Administration for psoriasis or other indications applied to AD patients. In their review of cases, they make the point that results are variable and anti-B-cell activity may hold the greatest promise.⁵ On the other hand, a recent series of 3 patients showed limited response to rituximab in chronic AD,⁶ while a combination of omalizumab, an anti-IgE medication, and rituximab was helpful in some patients.⁷ Ultimately, the issue is that nonspecific biologics may or may not address the underlying disease factors in AD. Therefore, there has been a true need for biologic intervention targeted directly at the pathogenic mechanism of AD. Furthermore, the desire for a biologic targeted at AD is paired with the true need to have a medication so targeted that the drug would have little effect on the rest of the immune system, resulting in targeted immunomodulation without secondary risk of infections.

Wait no longer, that era arrived a few months ago with the rapid US Food and Drug Administration approval of dupilumab, an injectable medication used every 2 weeks for the therapy of moderate to severe AD. This fully human monoclonal antibody against the IL-4Rα subunit blocks IL-4 and IL-13, key inflammatory agents in the triggering of production of IgE and eosinophil activation. Even better than the fact that it is targeted are the excellent outcomes in the therapy of moderate to severe AD in adults and the minimal side-effect profile resulting in no requirements for laboratory screening or ongoing monitoring.⁸

Dupilumab seems to perform well, both clinically and in improving the lives of AD patients. Meta-analysis of trials involving dupilumab has shown improved health-related quality of life outcomes.^9,10 Usage of dupilumab alone in clinical trials for 16 weeks (SOLO 1 and SOLO 2) has resulted in stunning reduction in disease severity with a limited side-effect profile, with patients most commonly reporting conjunctivitis.¹¹ In real-world models where dupilumab is added into a regimen of topical corticosteroid usage (LIBERTY AD CHRONOS trial), patients fared even better with the combination, highlighting that this medication may best be used adjunctively to our skin care guidance as dermatologists.¹²

A new era for AD patients has arrived and we as practitioners are now fortunate to be able to therapeutically reach the worst cases of AD. The new era has only begun with dozens of new agents addressing a variety of interleukin pathways including IL-17 and IL-22 still under development. Ultimately, we hope that ongoing pediatric trials will allow us to glean the role of early disease intervention at the root cause of AD and address our abilities to prevent comorbidities and disease persistence. Will we be able to avert years of disabling disease? The future holds immense hope.

What advice do you give your patients today?

There is more scientific data supporting educational intervention with an eczema action plan as the core of prevention and therapy. Early institution of emollient therapy is preventive of approximately half of atopic dermatitis (AD) cases. Application of emollients immediately after bathing is best for improvement of skin hydration. The art of medicine is deciding how to pick emollients with patients. It is important to avoid patient's allergens, but ultimately the choice comes down to cold weather petrolatum and warm weather thick lotions or creams.

Therapy must still be individually tailored. Head and neck disease is best treated with nonsteroidal agents including low-strength topical corticosteroids and calcineurin inhibitors that have a black box warning, both of which have a track record of efficacy in the care of AD. A newer option is crisaborole, a topical phosphodiesterase inhibitor, which is an alternative for childhood and adult AD. For the body, any of these agents can be used comfortably, but often a mixture of topical corticosteroids of various strengths is chosen to address different sites of disease. When topical corticosteroids fail, the usage of systemic agents or phototherapy may be appropriate. The new prescription injectable dupilumab is approved for adults with AD and therapies such as these will hopefully soon be available for children with severe disease who need intervention to improve their quality of life. 

How have you integrated new medications? How do you deal with side effects?

For all the therapies that truly work for AD, there are still many patients with limited to poor response on standard regimens and I offer them newer options and I also review their old regimens. Many patients believe they will be cured in 1 to 2 weeks and stop ongoing care. Counseling on the recurrent and relapsing nature of AD is important. On the other hand, I have AD patients who believe they had or truly have steroid sensitivity including allergy or withdrawal syndromes. I have seen topical steroid atrophy in this setting due to lack of intermittent discontinuation. Other situations in which topical steroid side effects are common in my practice are in the application sites of the thigh and calf in teenaged girls and the chest in teenaged boys, sites where striae are not uncommon naturally during adolescence. In these settings, confirmation of allergy via patch testing may be helpful and offering nonsteroidal agents can allow for remission of disease. Side effects with nonsteroidal agents are common but usually mild including pruritus, burning, and stinging. It is common for these symptoms to dissipate with time; therefore, preemptive education is vital (ie, stopping and restarting a day later) as well as avoidance of application to recently washed skin and limited application initially. Steroid pretreatment sometimes aids in acceptance of a nonsteroidal agent.

What information do patients want to hear?

Patients and guardians believe there has to be a cure for AD and that it will be dietary in nature. They hope I will provide an avoidance diet that will rapidly clear the disease, which I wish was true. In reality, the nature of current research is such that long-term remissions and possible cure do lie on the horizon but today are not readily available. No one can bypass good skin care and the current treatment paradigm. Withdrawal diets may cause malnourishment in children and should not be undertaken without proof of allergy.

How do you deal with steroid phobia?

Steroid phobia has become a hot topic but has existed since the advent of topical agents. Steroid phobia can cause nonadherence and poor outcomes. In reality, many topical steroidal agents have good testing and approvals in younger children. Fear is a powerful motivator and hard to break. Therefore, parents/guardians may reasonably opt for nonsteroidal care, which is a fine option when it works. Although little data on real-world combination usage of nonsteroidal and steroidal agents exist, combinations in my practice often enhance clearance. 

What patient resources do you recommend? 

Quoting study data may be beneficial. One of my favorite studies is historic comparative data of hydrocortisone cream 1% and mometasone furoate cream 0.1% in 48 children with moderate to severe AD (Vernon et al). At completion of the study, mometasone performed better in clearance and the only patient who developed hypothalamic-pituitary-adrenal axis suppression was in the hydrocortisone arm. I use this study to explain to parents why a prescription-strength agent may produce better results with fewer side effects.

Online snake oils abound in AD and the sources for solid information I choose are the websites of the National Eczema Association as well as academic organizations such as the American Academy of Dermatology and the Society for Pediatric Dermatology. Membership in support groups and participation can help parents/guardians and children alike and allow access to early clinical trial data. I sometimes ask parents/guardians to review manufacturer websites to specifically look for quoted clinical trial data. Although all clinical trials are not equivalent, many better eczema care manufacturers have numerous clinical trials in support of their agents, which should give a parent some enhanced comfort level.  

Suggested Readings

• Chiang C, Eichenfield LF. Quantitative assessment of combination bathing and moisturizing regimens on skin hydration in atopic dermatitis. Pediatr Dermatol. 2009;26:273-278.  
• Juha'sz MLW, Curley RA, Rasmussen A, et al. Systematic review of the topical steroid addiction and steroid withdrawal phenomenon in children diagnosed with atopic dermatitis and treated with topical corticosteroids. J Dermatol Nurses Assoc. In press.
• Mueller SM, Itin P, Vogt DR, et al. Assessment of "corticophobia" as an indicator of non-adherence to topical corticosteroids: a pilot study. J Dermatolog Treat. 2017;28:104-111.  
• Shirley M. Dupilumab: first global approval. Drugs. 2017;77:1115-1121.
• Silverberg NB, Durán-McKinster C. Special considerations for therapy of pediatric atopic dermatitis. Dermatol Clin. 2017;35:351-363.
• Simpson EL, Chalmers JR, Hanifin JM, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134:818-823.
• Vernon HJ, Lane AT, Weston W. Comparison of mometasone furoate 0.1% cream and hydrocortisone 1.0% cream in the treatment of childhood atopic dermatitis. J Am Acad Dermatol. 1991;24:603-607.

What advice do you give your patients today?

There is more scientific data supporting educational intervention with an eczema action plan as the core of prevention and therapy. Early institution of emollient therapy is preventive of approximately half of atopic dermatitis (AD) cases. Application of emollients immediately after bathing is best for improvement of skin hydration. The art of medicine is deciding how to pick emollients with patients. It is important to avoid patient's allergens, but ultimately the choice comes down to cold weather petrolatum and warm weather thick lotions or creams.

Therapy must still be individually tailored. Head and neck disease is best treated with nonsteroidal agents including low-strength topical corticosteroids and calcineurin inhibitors that have a black box warning, both of which have a track record of efficacy in the care of AD. A newer option is crisaborole, a topical phosphodiesterase inhibitor, which is an alternative for childhood and adult AD. For the body, any of these agents can be used comfortably, but often a mixture of topical corticosteroids of various strengths is chosen to address different sites of disease. When topical corticosteroids fail, the usage of systemic agents or phototherapy may be appropriate. The new prescription injectable dupilumab is approved for adults with AD and therapies such as these will hopefully soon be available for children with severe disease who need intervention to improve their quality of life. 

How have you integrated new medications? How do you deal with side effects?

For all the therapies that truly work for AD, there are still many patients with limited to poor response on standard regimens and I offer them newer options and I also review their old regimens. Many patients believe they will be cured in 1 to 2 weeks and stop ongoing care. Counseling on the recurrent and relapsing nature of AD is important. On the other hand, I have AD patients who believe they had or truly have steroid sensitivity including allergy or withdrawal syndromes. I have seen topical steroid atrophy in this setting due to lack of intermittent discontinuation. Other situations in which topical steroid side effects are common in my practice are in the application sites of the thigh and calf in teenaged girls and the chest in teenaged boys, sites where striae are not uncommon naturally during adolescence. In these settings, confirmation of allergy via patch testing may be helpful and offering nonsteroidal agents can allow for remission of disease. Side effects with nonsteroidal agents are common but usually mild including pruritus, burning, and stinging. It is common for these symptoms to dissipate with time; therefore, preemptive education is vital (ie, stopping and restarting a day later) as well as avoidance of application to recently washed skin and limited application initially. Steroid pretreatment sometimes aids in acceptance of a nonsteroidal agent.

What information do patients want to hear?

Patients and guardians believe there has to be a cure for AD and that it will be dietary in nature. They hope I will provide an avoidance diet that will rapidly clear the disease, which I wish was true. In reality, the nature of current research is such that long-term remissions and possible cure do lie on the horizon but today are not readily available. No one can bypass good skin care and the current treatment paradigm. Withdrawal diets may cause malnourishment in children and should not be undertaken without proof of allergy.

How do you deal with steroid phobia?

Steroid phobia has become a hot topic but has existed since the advent of topical agents. Steroid phobia can cause nonadherence and poor outcomes. In reality, many topical steroidal agents have good testing and approvals in younger children. Fear is a powerful motivator and hard to break. Therefore, parents/guardians may reasonably opt for nonsteroidal care, which is a fine option when it works. Although little data on real-world combination usage of nonsteroidal and steroidal agents exist, combinations in my practice often enhance clearance. 

What patient resources do you recommend? 

Quoting study data may be beneficial. One of my favorite studies is historic comparative data of hydrocortisone cream 1% and mometasone furoate cream 0.1% in 48 children with moderate to severe AD (Vernon et al). At completion of the study, mometasone performed better in clearance and the only patient who developed hypothalamic-pituitary-adrenal axis suppression was in the hydrocortisone arm. I use this study to explain to parents why a prescription-strength agent may produce better results with fewer side effects.

Online snake oils abound in AD and the sources for solid information I choose are the websites of the National Eczema Association as well as academic organizations such as the American Academy of Dermatology and the Society for Pediatric Dermatology. Membership in support groups and participation can help parents/guardians and children alike and allow access to early clinical trial data. I sometimes ask parents/guardians to review manufacturer websites to specifically look for quoted clinical trial data. Although all clinical trials are not equivalent, many better eczema care manufacturers have numerous clinical trials in support of their agents, which should give a parent some enhanced comfort level.  

Suggested Readings

• Chiang C, Eichenfield LF. Quantitative assessment of combination bathing and moisturizing regimens on skin hydration in atopic dermatitis. Pediatr Dermatol. 2009;26:273-278.  
• Juha'sz MLW, Curley RA, Rasmussen A, et al. Systematic review of the topical steroid addiction and steroid withdrawal phenomenon in children diagnosed with atopic dermatitis and treated with topical corticosteroids. J Dermatol Nurses Assoc. In press.
• Mueller SM, Itin P, Vogt DR, et al. Assessment of "corticophobia" as an indicator of non-adherence to topical corticosteroids: a pilot study. J Dermatolog Treat. 2017;28:104-111.  
• Shirley M. Dupilumab: first global approval. Drugs. 2017;77:1115-1121.
• Silverberg NB, Durán-McKinster C. Special considerations for therapy of pediatric atopic dermatitis. Dermatol Clin. 2017;35:351-363.
• Simpson EL, Chalmers JR, Hanifin JM, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134:818-823.
• Vernon HJ, Lane AT, Weston W. Comparison of mometasone furoate 0.1% cream and hydrocortisone 1.0% cream in the treatment of childhood atopic dermatitis. J Am Acad Dermatol. 1991;24:603-607.

What advice do you give your patients today?

There is more scientific data supporting educational intervention with an eczema action plan as the core of prevention and therapy. Early institution of emollient therapy is preventive of approximately half of atopic dermatitis (AD) cases. Application of emollients immediately after bathing is best for improvement of skin hydration. The art of medicine is deciding how to pick emollients with patients. It is important to avoid patient's allergens, but ultimately the choice comes down to cold weather petrolatum and warm weather thick lotions or creams.

Therapy must still be individually tailored. Head and neck disease is best treated with nonsteroidal agents including low-strength topical corticosteroids and calcineurin inhibitors that have a black box warning, both of which have a track record of efficacy in the care of AD. A newer option is crisaborole, a topical phosphodiesterase inhibitor, which is an alternative for childhood and adult AD. For the body, any of these agents can be used comfortably, but often a mixture of topical corticosteroids of various strengths is chosen to address different sites of disease. When topical corticosteroids fail, the usage of systemic agents or phototherapy may be appropriate. The new prescription injectable dupilumab is approved for adults with AD and therapies such as these will hopefully soon be available for children with severe disease who need intervention to improve their quality of life. 

How have you integrated new medications? How do you deal with side effects?

For all the therapies that truly work for AD, there are still many patients with limited to poor response on standard regimens and I offer them newer options and I also review their old regimens. Many patients believe they will be cured in 1 to 2 weeks and stop ongoing care. Counseling on the recurrent and relapsing nature of AD is important. On the other hand, I have AD patients who believe they had or truly have steroid sensitivity including allergy or withdrawal syndromes. I have seen topical steroid atrophy in this setting due to lack of intermittent discontinuation. Other situations in which topical steroid side effects are common in my practice are in the application sites of the thigh and calf in teenaged girls and the chest in teenaged boys, sites where striae are not uncommon naturally during adolescence. In these settings, confirmation of allergy via patch testing may be helpful and offering nonsteroidal agents can allow for remission of disease. Side effects with nonsteroidal agents are common but usually mild including pruritus, burning, and stinging. It is common for these symptoms to dissipate with time; therefore, preemptive education is vital (ie, stopping and restarting a day later) as well as avoidance of application to recently washed skin and limited application initially. Steroid pretreatment sometimes aids in acceptance of a nonsteroidal agent.

What information do patients want to hear?

Patients and guardians believe there has to be a cure for AD and that it will be dietary in nature. They hope I will provide an avoidance diet that will rapidly clear the disease, which I wish was true. In reality, the nature of current research is such that long-term remissions and possible cure do lie on the horizon but today are not readily available. No one can bypass good skin care and the current treatment paradigm. Withdrawal diets may cause malnourishment in children and should not be undertaken without proof of allergy.

How do you deal with steroid phobia?

Steroid phobia has become a hot topic but has existed since the advent of topical agents. Steroid phobia can cause nonadherence and poor outcomes. In reality, many topical steroidal agents have good testing and approvals in younger children. Fear is a powerful motivator and hard to break. Therefore, parents/guardians may reasonably opt for nonsteroidal care, which is a fine option when it works. Although little data on real-world combination usage of nonsteroidal and steroidal agents exist, combinations in my practice often enhance clearance. 

What patient resources do you recommend? 

Quoting study data may be beneficial. One of my favorite studies is historic comparative data of hydrocortisone cream 1% and mometasone furoate cream 0.1% in 48 children with moderate to severe AD (Vernon et al). At completion of the study, mometasone performed better in clearance and the only patient who developed hypothalamic-pituitary-adrenal axis suppression was in the hydrocortisone arm. I use this study to explain to parents why a prescription-strength agent may produce better results with fewer side effects.

Online snake oils abound in AD and the sources for solid information I choose are the websites of the National Eczema Association as well as academic organizations such as the American Academy of Dermatology and the Society for Pediatric Dermatology. Membership in support groups and participation can help parents/guardians and children alike and allow access to early clinical trial data. I sometimes ask parents/guardians to review manufacturer websites to specifically look for quoted clinical trial data. Although all clinical trials are not equivalent, many better eczema care manufacturers have numerous clinical trials in support of their agents, which should give a parent some enhanced comfort level.  

Suggested Readings

• Chiang C, Eichenfield LF. Quantitative assessment of combination bathing and moisturizing regimens on skin hydration in atopic dermatitis. Pediatr Dermatol. 2009;26:273-278.  
• Juha'sz MLW, Curley RA, Rasmussen A, et al. Systematic review of the topical steroid addiction and steroid withdrawal phenomenon in children diagnosed with atopic dermatitis and treated with topical corticosteroids. J Dermatol Nurses Assoc. In press.
• Mueller SM, Itin P, Vogt DR, et al. Assessment of "corticophobia" as an indicator of non-adherence to topical corticosteroids: a pilot study. J Dermatolog Treat. 2017;28:104-111.  
• Shirley M. Dupilumab: first global approval. Drugs. 2017;77:1115-1121.
• Silverberg NB, Durán-McKinster C. Special considerations for therapy of pediatric atopic dermatitis. Dermatol Clin. 2017;35:351-363.
• Simpson EL, Chalmers JR, Hanifin JM, et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J Allergy Clin Immunol. 2014;134:818-823.
• Vernon HJ, Lane AT, Weston W. Comparison of mometasone furoate 0.1% cream and hydrocortisone 1.0% cream in the treatment of childhood atopic dermatitis. J Am Acad Dermatol. 1991;24:603-607.

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Atopic dermatitis (AD) is a disease that finally is coming of age in dermatology research. New topical agents and systemic biologic agents offer patients with AD other options for medical management. This article provides a practical review of prevention strategies and treatment guidelines for AD.

PREVENTION

Prevention strategies for AD have been largely unsuccessful in the past, which may relate to factors such as prenatal triggers.¹ However, some newer interventional studies have shown some promise in AD prevention in specific settings. For example, a randomized trial of infants in the United States and United Kingdom at high risk for AD (ie, family history of atopy) reported that the AD risk was reduced by 50% when patients were treated with at least once-daily application of full-body emollients for 6 months (beginning by 3 weeks of life).² The strategy of daily application of emollients for avoidance of AD in infants with a family history of AD is reasonable but may not offer lifetime prevention, and the benefit in children not from AD families is unknown.

Other trials to prevent AD have included usage of dust avoidance and dust covers for mattresses. This strategy showed modest benefit in reducing the incidence of atopic diatheses in the first year³ but did not gain endorsement by the most recent guidelines of the American Academy of Dermatology (AAD).⁴

Prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus has shown promise in prevention.⁵ The exact regimen likely makes an impact on efficacy. An early study showed the usage of probiotics (eg, Lactobacillus reuteri) prenatally in pregnant women and postnatally in infants resulted in no reduction in occurrence of AD and possible reduction in IgE-associated AD.⁶ Kalliomäki et al⁷ demonstrated that L rhamnosus GG alone reduced AD by half in at-risk infants in a double-blind, placebo-controlled trial. On the other hand, Taylor et al⁸ performed a study of probiotic supplementation in which patients at high risk for AD developed higher rates of allergen sensitization. The most successful recent trial involved the randomization of 415 pregnant women to receive interventions from 36 weeks’ gestation until 3 months postpartum.⁹ The intervention was a randomized comparison of milk without probiotics versus a blend of probiotic milk containing L rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis subsp lactis Bb-12. At 6 years of age, 81 babies who consumed probiotic milk and 82 babies who consumed milk without probiotics were available for testing. The strategy caused a statistically significant reduction in AD in the complete case analysis (odds ratio, 0.48; 95% confidence interval, 0.25-0.92; P=.027; number needed to treat, 6). Sadly, other allergic diseases were not prevented in this study.⁹

MANAGEMENT OF AD

There currently is no cure or perfected prevention technique for AD. As a result, therapy focuses on avoiding triggers and alleviating symptoms.¹⁰ Recent guidelines from the AAD state that“[t]he ultimate judgment regarding the propriety of any specific therapy must be made by the physician and the patient in light of all the circumstances presented by the individual patient, and the known variability and biologic behavior of the disease.”¹¹ Skin-directed therapies are the first line of treatment including emollients, gentle skin care, and topical medicaments. In AD, therapies are needed to reduce disease activity and flare severity, clear flares, and provide relief.

Parental education and written eczema action plans are recommended to help patients and parents/guardians follow recommended regimens¹²; Tollefson and Bruckner¹³ for the American Academy of Pediatrics provide an action plan to guide the care of children with atopic dermatitis that is simple, but many others exist online. The eczema action plan usually provides information on how to bathe and what to do when the skin is actively inflamed.

In 2014, a 4-part series of guidelines of care for the management of AD was published by the AAD, replacing prior guidelines.^4,11,14,15 The following sections review some of the important parameters of care highlighted in these management guidelines.

Psychological Support

Appropriate psychological support for AD patients can be sought through counselors, therapists, psychiatrists, and support groups such as the National Eczema Association (https://nationaleczema.org/).

Education

Education is the leading form of medical therapy in patients with AD. Eczema schools are popular in Europe and are just beginning to form in the United States (http://tuh.templehealth.org/content/eczema_school.htm), which can be helpful to educate caregivers and patients with AD. Patient resources online and through support groups with an online presence, in-person meetings, and patient/family conventions can be helpful to AD patients. Often, an initial office visit with a dermatologist involves a review of avoidance of triggers, usage of gentle skin care including bland emollients, and therapeutic regimens for disease activity. This form of verbal education is to be paired with an eczema action plan, a written document that allows individuals to reference recommendations and share information with other caregivers.^12,13,16

Emollients and Gentle Skin Care

Gentle skin care regimens, which includes the usage of synthetic cleansers with a low pH to help maintain the acidity (acid mantle) of the skin, seek to reduce irritation and have been rated as level IA (highest level) in recent AAD guidelines.¹⁴ Although bathing frequency has been emphasized in the guidelines, AD severity as reflected by SCORAD (SCORing Atopic Dermatitis) was not different for daily bathing versus twice weekly.¹⁷ The American Academy of Pediatrics recommended a skin care regimen of bathing every 2 to 3 days in lukewarm water for 10 to 15 minutes, followed by application of emollients that are fragrance free and have few preservatives.¹³ Topical emollients with additives such as colloidal oatmeal, avenanthramides, or ceramides can be used to enhance the skin barrier and are well tolerated in all age groups.^18,19 Despite enhanced emollients, the therapy of AD still requires usage of prescription or over-the-counter TCs and/or topical calcineurin inhibitors (TCIs) in many cases.²⁰

Topical Medication

Children have a relatively higher body surface area–to-weight ratio, allowing for greater potential absorption of topical medicaments and potential side effects from absorption. Types of vehicle, cost, site of application, and availability may impact patient and physician preference in choice of therapeutic topical agent.¹⁴

Topical Corticosteroids
Topical corticosteroids (TCs) are the mainstay of treatment for AD and have been used for more than 60 years^.14,20 Topical corticosteroids provide anti-inflammatory effects on T cells, monocytes, and macrophages, producing altered cytokine activity locally. Topical corticosteroids inhibit collagen synthesis, potentially causing skin atrophy. They also inhibit IL-1, IL-2, IL-6, IFN-α, and tumor necrosis factor α.²¹ Topical corticosteroids are classified as class I (ultra-high potency) to class VII (low potency). In children, low-potency TCs generally are applied to the face, intertriginous areas, groin, and genitalia, and mid-potency corticosteroids are applied to the body, arms, and legs. An even higher-strength agent can be prescribed as a rescue medication in severe cases. After clearance with once- or twice-daily therapy, twice-weekly usage can benefit disease activity.²² Topical corticosteroids reduce inflammation as well as Staphylococcus aureus load through inhibition of cytokines that inhibit antimicrobial peptides. Topical corticosteroids have been endorsed as level IA evidence therapy by the AAD guidelines.¹⁴

Topical corticosteroids, particularly prolonged usage of mid- to high-potency products, have been associated with side effects such as skin atrophy, striae, telangiectases, hypopigmentation, rosacea, acneiform eruptions, focal hypertrichosis, perioral dermatitis, and acne²³; potential systemic side effects include hypothalamic-pituitary-adrenal axis suppression, cataracts, glaucoma (with periocular application), Cushing syndrome, hyperglycemia, hypertension,²³ and growth retardation.¹⁴ Long-term corticosteroid therapy is associated with tachyphylaxis and potential rebound of disease with discontinuation.²⁴ Based on the potential risk of side effects with TCs, the least potent product for the shortest time needed is recommended, with special care for thin skin. Discontinuation when clearance occurs is advised. Allergy to TCs and/or vehicle ingredients such as propylene glycol should be suspected in severe unremitting cases.¹⁴ A recent registry review of children screened for contact dermatitis demonstrated that children with AD had higher sensitization to the steroid tixocortol pivalate.²⁵

Topical Calcineurin Inhibitors
Topical calcineurin inhibitors include pimecrolimus cream 1%, which is approved for mild to moderate AD in adults and children 2 years and older, and tacrolimus ointment 0.03% and 0.1%, which are approved for moderate to severe AD in adults and children aged 2 to 15 years (0.03% formulation only). Topical calcineurin inhibitors can be used as second-line agents in AD in patients who have inadequate response to TCs or who may not be able to use TCs due to the disease site.^10,13,14 Guidelines from the AAD also have endorsed TCIs as level IA evidence for steroid-sparing agents.

Concerns about the reporting of cancers and lymphomas prompted the US Food and Drug Administration to issue a black box warning on TCIs more than 10 years ago. Pimecrolimus, which has little absorption and no notable immunosuppressive effects, has been used without detrimental effect on vaccination and delayed-type hypersensitivities, but many decades of data are lacking.^{10,13,14,17,26-29} Topical calcineurin inhibitors can be used as steroid-sparing agents in lieu of corticosteroids in specific locations such as the face and eyelids and for long-term suppressive therapy twice weekly.³⁰ Intermittent usage and cycling with corticosteroids is advisable,²⁸ but usage intermittently beyond 1 year has not been evaluated.

Topical calcineurin inhibitors are recommended as effective for acute and chronic AD. Their use as maintenance therapy in adults and children, for AD recalcitrant to steroids, for AD in sensitive areas, for steroid-induced atrophy, and for long-term uninterrupted topical steroid usage carries a level IA evidence recommendation. Furthermore, the AAD guidelines have recommended TCIs as steroid-sparing agents with level IA evidence and off-label use of TCIs in children younger than 2 years with level IA evidence. Pretreatment with TCs to reduce stinging has level IIB evidence. Usage for flare prevention is level IA evidence. Routine blood monitoring of TCI-treated patients was not recommended; in fact, the AAD guidelines provided this recommendation as level IA evidence against routine laboratory monitoring of TCI-treated patients.¹⁴

Topical Antibiotics
Topical antibiotics are indicated for the therapy of impetigo and can be used in the setting of impetiginized AD in conjunction with TCs. Recent AAD guidelines suggested against routine usage of topical antistaphylococcal agents as level IA evidence.¹⁴ There is one study supporting usage of topical mupirocin in addition to TCs to heal children with eczema area and severity index scores more than 7 more rapidly in the first week of AD therapy, but in the same study, additive benefit was not demonstrated in AD beyond the first week.³¹ There also are data supporting usage of intranasal mupirocin adjunctively with bleach baths in patients with moderate to severe AD, which was rated as level IIB evidence in the AAD guidelines.^14,32 There are limited data on the long-term utility of topical anti-infectives in AD. The risks of long-term usage could include resistance formation to agents such as mupirocin, contact dermatitis, and lack of efficacy.

Additional Therapeutics

Wet Wraps
Penetration through the stratum corneum is needed for drug activity in AD. Penetration can be enhanced using wet wrap therapy or using ointments, which produce higher relative potency.¹³ Wet wraps overlying a dilute topical medicament have been described as effective in AD and are recommended in AAD guidelines as level IIB evidence.¹⁴ Different wet wrap techniques can be used, including wet pajamas covered by dry pajamas or saline-soaked gauze wrapped around the affected areas and then dry gauze applied over the wet gauze. The methodology used should be tailored to the patient as well as to whether the individual is an inpatient or outpatient.

Bleach Baths
Dilute sodium hypochlorite solution 0.005% (one-quarter cup bleach in 20 gallons of water) has been demonstrated to be beneficial in reduction of disease activity in AD patients with recurrent bacterial infections.³² This simple technique in addition to intranasal mupirocin can reduce AD severity and improve quality of life and is the only ongoing S aureus therapeutic management endorsed by the AAD guidelines for the management of AD.^14,32

Topical and Oral Delivery

Antihistamines
Topical antihistamines are ineffective in AD. Oral antihistamines can be used to reduce pruritus and are most effective when given as sedating agents for sleep enhancement but may be given as nonsedating agents for patients with concomitant allergic disorders such as allergic rhinoconjunctivitis. Paradoxical hyperreactivity with sedating antihistamines is not uncommon in small children, and sedating antihistamine usage should be discontinued in these instances.¹³ Parents of children with AD have reported giving the child antihistamines to sleep was helpful, as well as putting on creams, using special clothes (eg, all cotton), and keeping the room cool.³³ There is level IIIC evidence against use of systemic antihistamines and level IIA evidence for sedating and nonsedating, according to the AAD guidelines.¹⁴

Systemic Therapeutics

Oral therapeutics range from oral antihistamines to oral antibiotics and immunosuppressive medications. Oral antibiotics (level IIB evidence) are reserved for superinfected AD, which is not easily defined for the following reasons: there is no consensus definition of superinfected AD; the majority of active AD lesions when cultured will demonstrate S aureus growth; and most AD lesions ooze, thereby creating the appearance of superinfection. In real-world practice, superinfection can be diagnosed based on the presence of pustules; furuncles; or signs of infection such as tracking erythema, tenderness, severe erosions, or maceration. Clinical judgment is always required.

The immunosuppressive medications used in AD include leukotriene inhibitors, which rarely are effective for AD.³⁴ More effective systemic agents for AD include cyclosporine (level I to IIB evidence), azathioprine (level IIB evidence), mycophenolate mofetil (level IIIC evidence), and methotrexate (level IIB evidence). These agents are indicated for pediatric or adult patients when topical agents and/or phototherapy have failed.¹⁵ Monitoring these agents for side effects includes ongoing evaluation for renal and liver toxicity. Short courses (ie, 6 months) are preferred to minimize side effects.³⁵

Dupilumab, an injectable AD therapy, is approved in the United States. This agent is injected every 2 weeks and binds to the IL-4Rα shared by IL-4 and IL-13. In 4 weeks of monotherapy, 85% of adult patients treated had 50% or greater clearance.³⁶ Recently published consensus opinion from the International Eczema Council recommends assessment of a variety of factors before initiating systemic therapy including comorbid illnesses such as contact allergy, trigger avoidance, superinfection, and impact on quality of life.³⁷

Oral Corticosteroids
Systemic corticosteroids clear patients quickly but provide no sustained improvement; in fact, many patients rebound or have tachyphylaxis. Although short-term corticosteroid usage can break the itch-scratch cycle, long-term usage is associated with osteoporosis, Cushing syndrome, and aseptic necrosis of the femoral head. Decreased linear growth will occur during therapy in children; therefore, systemic steroids are not recommended in children with AD, except for additional or comorbid conditions (eg, asthma or contact dermatitis).⁴

Phototherapy
Phototherapy has been recommended in the AAD guidelines as a second-line treatment after failure of first-line agents (ie, TCIs and TCs) for clearance and or maintenance and should be tailored to the patient’s skin tone by an experienced physician. Narrowband UVB phototherapy may act through the suppression of T-cell activity in the skin and possibly via suppression of staphylococcal superantigens; however, many phototherapy types have been described for AD.^38,39 Usage can be effective in school-aged children and teenagers but may be limited due to school attendance. Phototherapy was graded as level IIB evidence in the AAD guidelines.¹⁵ Side effects include aggravation of AD by exposure to heat and UV light, actinic damage, tenderness, erythema, pruritus, burning, and stinging. Lentigines; skin cancers (melanoma and nonmelanoma); folliculitis; and ocular toxicity, especially cataracts, can occur.¹⁵ Children younger than 6 years will find it difficult to stand in a phototherapy booth and may be poor candidates.^15,38,39

Complementary and Alternative Medicine

Complementary and alternative medicine (CAM) also has been used for AD in the United States. In a review of the 2007 National Health Interview Survey of 9417 children aged 0 to 17 years, CAM was used for AD by 0.99% of children. Some CAM techniques were associated with worsening severity of AD, including herbal therapy, vitamins, homeopathic agents, diet, and movement techniques.⁴⁰ Usage of Chinese herbal medications for AD can be associated with liver toxicity.⁴¹ Only one CAM therapy—massage therapy—has some mild supportive data.⁴²

Allergen Avoidance and Diet
Bronsnick et al⁴³ discussed the possible benefit of prenatal and postnatal probiotics for prevention of AD, which were not supported in the AAD guidelines for management of AD⁴; postnatal prebiotic supplementation; and exclusive breastfeeding and/or supplementation with hydrolyzed formula in at-risk children. Elimination diets for children and mothers were not recommended. The authors found no beneficial role of supplements including vitamin D, selenium, fish oil, borage oil, and zinc sulfate.⁴³

A National Institute of Allergy and Infectious Diseases consensus group recommended avoidance of proven but not random elimination of food allergens in AD, asthma, and/or eosinophilic esophagitis.⁴⁴ Restricted maternal diet was not recommended, and breastfeeding exclusively for the first 4 to 6 months was recommended. Hydrolyzed formulas were suggested as a possible preventive strategy in at-risk infants as a breastfeeding alternative, with cost of these formulas being a problem.⁴⁴

In children younger than 5 years, food allergy screening for the most common allergens (eg, milk, eggs, peanuts, wheat, soy) should be considered in children with persistent unremitting dermatitis and/or known food challenge–induced reactions.⁴ Conservative measures to avoid house dust mite exposure in known sensitized individuals including dust covers for pillows and mattresses may be beneficial.^4,45

Emerging Therapies

Recently approved therapies include better-targeted agents that appear to have a reasonable safety profile and may fulfill unmet needs in AD care. Of these agents, crisaborole, a topical boron-based phosphodiesterase 4 inhibitor, was approved in December 2016 for mild to moderate AD in patients 2 years and older.Topically, this agent seems to be efficacious in the absence of notable carcinogenicity.⁴⁶

The systemic (injectable) biologic agent dupilumab was approved in March 2017 for moderate to severe AD. Phase 3 studies in adults with AD showed excellent success in adults with moderate to severe AD.³⁷ This agent is a monoclonal antibody targeted at blockade of the crucial atopic inflammatory triggering pathway via blockade of the IL-4A receptor site, targeting IL-4 and IL-13 activity.^36,47 There are many medications in the pipeline, which Renert-Yuval and Guttman-Yassky⁴⁸ review. However, an overview of the landscape demonstrates that Janus kinase (JAK) inhibitors⁴⁹ and biologic medications in addition to dupilumab affecting targeted inflammatory cascades in AD are in development. In particular, the JAK inhibitors appear promising due to availability both as oral and topical agents.⁴⁹

Need for Ongoing Care and Monitoring

Atopic dermatitis is a chronic inflammatory skin disorder with a genetic basis. Once initiated, the process of AD may persist throughout the patient’s life and become a systemic disorder with comorbidities including sleep disturbance, reduced quality of life, and cardiovascular disease.⁵⁰ Ongoing management of AD includes topical reduction in irritants and triggers, topical medicaments, and management of pruritus and infections. At this time, emollients and irritant avoidance paired with judicious topical medicaments including TCs and second-line or site-specific (eg, eyelids) usage of TCIs or phosphodiesterase 4 inhibitors remain the backbone of therapy. Ongoing review of therapeutics for associated morbidities is underway, which may guide future therapeutic interventions into AD. The future of prevention and therapy look bright, but time will tell.

Atopic dermatitis (AD) is the most common inflammatory skin condition, affecting approximately 15% to 20% of the global population.^1,2 Atopic dermatitis is characterized by a chronic relapsing dermatitis with pruritus, often beginning in infancy or childhood. Atopic dermatitis is caused by a defect in epidermal barrier function, which results in increased transepidermal water loss.¹ The criteria for AD include a pruritic skin condition plus 3 or more of the following: history of involvement of the skin creases, history of asthma or hay fever, history of AD in a first-degree relative (in children), 1-year history of generally dry skin, visible flexural eczema, and an age of onset of less than 2 years. Adults with AD frequently present with hand or facial dermatitis.¹

UV light therapies including narrowband UVB (NB-UVB), UVA1, and psoralen plus UVA (PUVA) have all been used as effective treatments of AD.^3,4 UV light is beneficial for AD patients due to its immunomodulatory effects, thickening of the stratum corneum, and the reduction of Staphylococcus aureus in the skin.² Most patients with AD improve with light therapy; however, it is estimated that 1% to 3% of patients with AD will experience a paradoxical worsening of their AD after exposure to UV light.^2,5 This condition is referred to as photosensitive AD and is characterized by a photodistributed rash in patients who fulfill the criteria of AD. Photosensitive AD has a female predominance and generally affects patients with late-onset disease with development of AD after puberty.^2,5 The pathogenesis for the development of photosensitivity in patients with AD who previously tolerated exposure to sunlight is unknown.⁵ We describe a case of photosensitive AD exacerbated by UVB exposure.

Case Report

A 55-year-old Asian woman presented for evaluation of a rash on the head, neck, and arms. She reported that she had developed a pruritic rash with edema after sun exposure at 16 years of age. Since then, the rash has been intermittent and completely resolved at times with periods of decreased sun exposure; however, the rash recently had been persistent and worsening despite practicing strict sun protection with daily sunscreen application, protective clothing, and sun avoidance. She was not taking systemic medications or supplements at the time but was applying high-potency topical corticosteroids and calcineurin inhibitors with minimal improvement under the care of a dermatologist.

On physical examination the patient had thin, well-demarcated, erythematous papules and plaques with scaling, primarily on sun-exposed skin on the forehead (Figure 1A), cheeks (Figure 1B), eyelids, upper lip, neck (Figures 1B and 1C), upper chest (Figure 1C), and dorsal aspect of the hands, with excoriated pink papules on the forearms, shoulders, and back. A punch biopsy of the right neck showed spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate (Figure 2). Further workup was pursued including complete blood cell count, comprehensive metabolic profile, liver function panel, Sjögren syndrome antigen A/Sjögren syndrome antigen B test, antinuclear antibody test, human immunodeficiency virus 1/2 antigen/antibody test, hepatitis panel, and mycobacterium tuberculosis test, which were all within reference range. Photodermatosis was suspected and she underwent phototesting including UVA, NB-UVB, and visible light. Phototesting confirmed she had a UVB photosensitivity with a markedly decreased minimal erythema dose (MED) to NB-UVB. The MED to NB-UVB was positive at 24 hours to all tested sites, the lowest of which was 0.135 J/cm². Eczematous changes began to develop at day 6 at doses of 0.945 and 1.080 J/cm². The patient also underwent visible light testing, which was negative. The patient was patch tested for multiple standardized agents as well as personal products, all of which were negative. Subsequent photopatch testing revealed a slightly positive reaction to benzophenone 4, a common ingredient in sunscreens.

The patient was then started on mycophenolate mofetil and prednisone. Repeat MED testing to NB-UVB was performed. Her repeat MED to NB-UVB was determined to be 0.405 J/cm², and hardening commenced at 3 times per week at 70% of the MED (0.2835 J/cm²). She began to flare and develop an eczematous reaction, thus the dose was decreased to 50% of the MED (0.2025 J/cm²), which she tolerated.

Comment

Classification and Clinical Presentation
The literature on photosensitive AD is scant, and this disease entity is rare. Alternative names include photoaggravated AD, photosensitive eczema, and light-exacerbated eczema.⁵ Two main studies have been conducted in recent years that were intended to characterize photosensitive AD. ten Berge et al⁵ conducted a retrospective study of 145 patients with AD that were phototested in 2009. They found that 3% of their total AD patient population had photosensitive AD.⁵ In 2016, Ellenbogen et al² performed a similar single-center retrospective analysis of 17 patients with long-standing AD who suddenly developed photosensitivity.

Patients with photosensitive AD typically present with lesions on sun-exposed skin with coexisting eczematous lesions in sites with a predilection for AD.² In the study conducted by ten Berge et al,⁵ 2 main reaction patterns were observed: erythematous papules with pruritus and an eczematous reaction. The authors suggested one subset of patients demonstrated polymorphous light eruption (PMLE), a common photoinduced eruption thought to represent a delayed-type hypersensitivity, coexisting with AD while the other subset had true photosensitive AD.^5,6 Ellenbogen et al² also found 2 reaction patterns, which they labeled papular (PMLE type) and eczematous (photosensitive AD type). The authors contested the theory of coexisting PMLE in AD because PMLE gets better in the summer with UV radiation hardening.² On the contrary, photosensitive AD worsens with uncontrolled exposure to sunlight. Only with controlled exposure to small doses of UV radiation at a time does this condition improve. Ellenbogen et al² believe both reaction patterns are consistent with photosensitive AD and the PMLE type should be termed papular photosensitive AD type.

Histopathology
The histopathologic findings of photosensitive AD are nonspecific but are characterized by spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate.²

Diagnosis With Phototesting
Phototesting of patients with AD should be considered if there is a suspicion for photosensitivity based on persistent disease despite use of photoprotection and local treatment.^5-7 Patients may not notice a correlation of skin exacerbations with UV exposure, especially if they are only sensitive to UVA, as it is still present on cloudy days and can penetrate glass windows.⁸ Phototesting evaluates the degree of sensitivity to UV light and the specific wavelength eliciting the cutaneous response. Phototesting consists of determining the MED to UVA and UVB, the minimal phototoxic dose for PUVA, and visible light exposure. Further evaluation may include photoprovocation testing or photopatch testing, as these patients can have coexisting photocontact allergies.

The MED is defined as the minimal dose of UV light needed to induce perceptible erythema in exposed skin.⁵ It is dependent on the light source and patient’s skin type, and individual units may vary. To determine the MED to UVA or UVB, 2×2-cm skin fields are irradiated with increasing cumulative UVA/UVB. The dose varies by skin type and it is then read at 24 hours. The majority of patients with photosensitive AD are reported to have a normal MED; however, some studies have reported the MED to be decreased.^5,7-9 ten Berge et al⁵ found 7% of their study participants exhibited a lower MED, as seen in our patient.

The minimal phototoxic dose for PUVA is defined as the least exposure dose of UVA 1 hour after ingestion of 0.4 mg/kg of methoxsalen that produces pink erythema with 4 distinct borders at 48, 72, or 96 hours after ingestion.¹⁰ Visible light exposure is tested using a slide projector as the light source to an approximately 10×5-cm area of skin for 45 minutes. Any immediate or delayed reaction is abnormal and considered positive.¹⁰

Photoprovocation testing has been performed in several studies.^2,5 It consists of exposing an 8-cm area of skin to 80 J/cm² UVA and 10 mJ/cm² UVB, which is read at 24, 48, or 72 hours. A papular or eczematous reaction is considered positive.^2,11

The results of phototesting have varied between studies. ten Berge et al⁵ phototested 107 patients with AD and photosensitivity and 17% were found to be solely sensitive to UVA whereas 67% were found to be sensitive to UVA and UVB. In contrast, Ellenbogen et al² only tested 17 patients with AD and photosensitivity and they found that 56% (9/16) were sensitive to UVA alone while only 44% (7/16) were sensitive to UVA and UVB.

Photopatch testing can help to rule out photosensitivity due to a substance in the presence of UV light. In studies of patients with photosensitive AD (N=125), photocontact reactions occurred in 23% and were predominantly associated with sunscreens, skin care products, and fragrances.^5,12 Photopatch testing is done by placing duplicate sets of patches on nonlesional skin using the Finn Chamber technique. A published list of allergens, which were agreed upon by the European Society of Contact Dermatitis and the European Society for Photodermatology in 2000 are seen in Table 1.¹³ The list contains mainly UV filters and drugs. The patients’ own products also should be tested in addition to the published list of allergens, but a maximum of 30 patches should be placed at one time. The patches are removed at either 24 or 48 hours; some researchers have found greater sensitivity with the 48-hour time period, while others have not found a significant difference.¹⁰ One set of skin fields then is covered with an impermeable occlusive dressing as a control while the other is irradiated with 5 J/cm² of a broad-spectrum UVA light source. UVA fluorescent lamps are the light source of choice because of their widespread availability, reproducible broad spectrum, and beam uniformity.¹⁰ In the study conducted by ten Berge et al,⁵ photopatch testing was performed on 125 patients, and 29 patients were found to be positive to one or more substances. Ellenbogen et al² photopatch tested 5 patients with photosensitive AD and a clinical suspicion of photoallergy; however, all 5 were negative. Our patient underwent traditional patch testing due to clinical suspicion of a coexisting contact allergy, which was negative.

Conclusion

Photosensitive AD is a rare entity characterized by a photodistributed rash and involvement of non–sun-exposed skin. Patients will either have a history of AD or fulfill the criteria of AD. They have positive photoprovocation testing and generally have a normal MED. They may have positive photopatch testing with coexisting photoallergies. Histopathology is nonspecific but shows spongiotic dermatitis with perivascular lymphohistiocytic infiltrate. Diagnosis is essential, as this disease can be life altering and affect quality of life. Effective treatment options are available, and the therapeutic ladder is based on severity of disease.^2,5

Atopic dermatitis (AD) is the most common inflammatory skin condition, affecting approximately 15% to 20% of the global population.^1,2 Atopic dermatitis is characterized by a chronic relapsing dermatitis with pruritus, often beginning in infancy or childhood. Atopic dermatitis is caused by a defect in epidermal barrier function, which results in increased transepidermal water loss.¹ The criteria for AD include a pruritic skin condition plus 3 or more of the following: history of involvement of the skin creases, history of asthma or hay fever, history of AD in a first-degree relative (in children), 1-year history of generally dry skin, visible flexural eczema, and an age of onset of less than 2 years. Adults with AD frequently present with hand or facial dermatitis.¹

UV light therapies including narrowband UVB (NB-UVB), UVA1, and psoralen plus UVA (PUVA) have all been used as effective treatments of AD.^3,4 UV light is beneficial for AD patients due to its immunomodulatory effects, thickening of the stratum corneum, and the reduction of Staphylococcus aureus in the skin.² Most patients with AD improve with light therapy; however, it is estimated that 1% to 3% of patients with AD will experience a paradoxical worsening of their AD after exposure to UV light.^2,5 This condition is referred to as photosensitive AD and is characterized by a photodistributed rash in patients who fulfill the criteria of AD. Photosensitive AD has a female predominance and generally affects patients with late-onset disease with development of AD after puberty.^2,5 The pathogenesis for the development of photosensitivity in patients with AD who previously tolerated exposure to sunlight is unknown.⁵ We describe a case of photosensitive AD exacerbated by UVB exposure.

Case Report

A 55-year-old Asian woman presented for evaluation of a rash on the head, neck, and arms. She reported that she had developed a pruritic rash with edema after sun exposure at 16 years of age. Since then, the rash has been intermittent and completely resolved at times with periods of decreased sun exposure; however, the rash recently had been persistent and worsening despite practicing strict sun protection with daily sunscreen application, protective clothing, and sun avoidance. She was not taking systemic medications or supplements at the time but was applying high-potency topical corticosteroids and calcineurin inhibitors with minimal improvement under the care of a dermatologist.

On physical examination the patient had thin, well-demarcated, erythematous papules and plaques with scaling, primarily on sun-exposed skin on the forehead (Figure 1A), cheeks (Figure 1B), eyelids, upper lip, neck (Figures 1B and 1C), upper chest (Figure 1C), and dorsal aspect of the hands, with excoriated pink papules on the forearms, shoulders, and back. A punch biopsy of the right neck showed spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate (Figure 2). Further workup was pursued including complete blood cell count, comprehensive metabolic profile, liver function panel, Sjögren syndrome antigen A/Sjögren syndrome antigen B test, antinuclear antibody test, human immunodeficiency virus 1/2 antigen/antibody test, hepatitis panel, and mycobacterium tuberculosis test, which were all within reference range. Photodermatosis was suspected and she underwent phototesting including UVA, NB-UVB, and visible light. Phototesting confirmed she had a UVB photosensitivity with a markedly decreased minimal erythema dose (MED) to NB-UVB. The MED to NB-UVB was positive at 24 hours to all tested sites, the lowest of which was 0.135 J/cm². Eczematous changes began to develop at day 6 at doses of 0.945 and 1.080 J/cm². The patient also underwent visible light testing, which was negative. The patient was patch tested for multiple standardized agents as well as personal products, all of which were negative. Subsequent photopatch testing revealed a slightly positive reaction to benzophenone 4, a common ingredient in sunscreens.

The patient was then started on mycophenolate mofetil and prednisone. Repeat MED testing to NB-UVB was performed. Her repeat MED to NB-UVB was determined to be 0.405 J/cm², and hardening commenced at 3 times per week at 70% of the MED (0.2835 J/cm²). She began to flare and develop an eczematous reaction, thus the dose was decreased to 50% of the MED (0.2025 J/cm²), which she tolerated.

Comment

Classification and Clinical Presentation
The literature on photosensitive AD is scant, and this disease entity is rare. Alternative names include photoaggravated AD, photosensitive eczema, and light-exacerbated eczema.⁵ Two main studies have been conducted in recent years that were intended to characterize photosensitive AD. ten Berge et al⁵ conducted a retrospective study of 145 patients with AD that were phototested in 2009. They found that 3% of their total AD patient population had photosensitive AD.⁵ In 2016, Ellenbogen et al² performed a similar single-center retrospective analysis of 17 patients with long-standing AD who suddenly developed photosensitivity.

Patients with photosensitive AD typically present with lesions on sun-exposed skin with coexisting eczematous lesions in sites with a predilection for AD.² In the study conducted by ten Berge et al,⁵ 2 main reaction patterns were observed: erythematous papules with pruritus and an eczematous reaction. The authors suggested one subset of patients demonstrated polymorphous light eruption (PMLE), a common photoinduced eruption thought to represent a delayed-type hypersensitivity, coexisting with AD while the other subset had true photosensitive AD.^5,6 Ellenbogen et al² also found 2 reaction patterns, which they labeled papular (PMLE type) and eczematous (photosensitive AD type). The authors contested the theory of coexisting PMLE in AD because PMLE gets better in the summer with UV radiation hardening.² On the contrary, photosensitive AD worsens with uncontrolled exposure to sunlight. Only with controlled exposure to small doses of UV radiation at a time does this condition improve. Ellenbogen et al² believe both reaction patterns are consistent with photosensitive AD and the PMLE type should be termed papular photosensitive AD type.

Histopathology
The histopathologic findings of photosensitive AD are nonspecific but are characterized by spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate.²

Diagnosis With Phototesting
Phototesting of patients with AD should be considered if there is a suspicion for photosensitivity based on persistent disease despite use of photoprotection and local treatment.^5-7 Patients may not notice a correlation of skin exacerbations with UV exposure, especially if they are only sensitive to UVA, as it is still present on cloudy days and can penetrate glass windows.⁸ Phototesting evaluates the degree of sensitivity to UV light and the specific wavelength eliciting the cutaneous response. Phototesting consists of determining the MED to UVA and UVB, the minimal phototoxic dose for PUVA, and visible light exposure. Further evaluation may include photoprovocation testing or photopatch testing, as these patients can have coexisting photocontact allergies.

The MED is defined as the minimal dose of UV light needed to induce perceptible erythema in exposed skin.⁵ It is dependent on the light source and patient’s skin type, and individual units may vary. To determine the MED to UVA or UVB, 2×2-cm skin fields are irradiated with increasing cumulative UVA/UVB. The dose varies by skin type and it is then read at 24 hours. The majority of patients with photosensitive AD are reported to have a normal MED; however, some studies have reported the MED to be decreased.^5,7-9 ten Berge et al⁵ found 7% of their study participants exhibited a lower MED, as seen in our patient.

The minimal phototoxic dose for PUVA is defined as the least exposure dose of UVA 1 hour after ingestion of 0.4 mg/kg of methoxsalen that produces pink erythema with 4 distinct borders at 48, 72, or 96 hours after ingestion.¹⁰ Visible light exposure is tested using a slide projector as the light source to an approximately 10×5-cm area of skin for 45 minutes. Any immediate or delayed reaction is abnormal and considered positive.¹⁰

Photoprovocation testing has been performed in several studies.^2,5 It consists of exposing an 8-cm area of skin to 80 J/cm² UVA and 10 mJ/cm² UVB, which is read at 24, 48, or 72 hours. A papular or eczematous reaction is considered positive.^2,11

The results of phototesting have varied between studies. ten Berge et al⁵ phototested 107 patients with AD and photosensitivity and 17% were found to be solely sensitive to UVA whereas 67% were found to be sensitive to UVA and UVB. In contrast, Ellenbogen et al² only tested 17 patients with AD and photosensitivity and they found that 56% (9/16) were sensitive to UVA alone while only 44% (7/16) were sensitive to UVA and UVB.

Photopatch testing can help to rule out photosensitivity due to a substance in the presence of UV light. In studies of patients with photosensitive AD (N=125), photocontact reactions occurred in 23% and were predominantly associated with sunscreens, skin care products, and fragrances.^5,12 Photopatch testing is done by placing duplicate sets of patches on nonlesional skin using the Finn Chamber technique. A published list of allergens, which were agreed upon by the European Society of Contact Dermatitis and the European Society for Photodermatology in 2000 are seen in Table 1.¹³ The list contains mainly UV filters and drugs. The patients’ own products also should be tested in addition to the published list of allergens, but a maximum of 30 patches should be placed at one time. The patches are removed at either 24 or 48 hours; some researchers have found greater sensitivity with the 48-hour time period, while others have not found a significant difference.¹⁰ One set of skin fields then is covered with an impermeable occlusive dressing as a control while the other is irradiated with 5 J/cm² of a broad-spectrum UVA light source. UVA fluorescent lamps are the light source of choice because of their widespread availability, reproducible broad spectrum, and beam uniformity.¹⁰ In the study conducted by ten Berge et al,⁵ photopatch testing was performed on 125 patients, and 29 patients were found to be positive to one or more substances. Ellenbogen et al² photopatch tested 5 patients with photosensitive AD and a clinical suspicion of photoallergy; however, all 5 were negative. Our patient underwent traditional patch testing due to clinical suspicion of a coexisting contact allergy, which was negative.

Conclusion

Photosensitive AD is a rare entity characterized by a photodistributed rash and involvement of non–sun-exposed skin. Patients will either have a history of AD or fulfill the criteria of AD. They have positive photoprovocation testing and generally have a normal MED. They may have positive photopatch testing with coexisting photoallergies. Histopathology is nonspecific but shows spongiotic dermatitis with perivascular lymphohistiocytic infiltrate. Diagnosis is essential, as this disease can be life altering and affect quality of life. Effective treatment options are available, and the therapeutic ladder is based on severity of disease.^2,5

Atopic dermatitis (AD) is the most common inflammatory skin condition, affecting approximately 15% to 20% of the global population.^1,2 Atopic dermatitis is characterized by a chronic relapsing dermatitis with pruritus, often beginning in infancy or childhood. Atopic dermatitis is caused by a defect in epidermal barrier function, which results in increased transepidermal water loss.¹ The criteria for AD include a pruritic skin condition plus 3 or more of the following: history of involvement of the skin creases, history of asthma or hay fever, history of AD in a first-degree relative (in children), 1-year history of generally dry skin, visible flexural eczema, and an age of onset of less than 2 years. Adults with AD frequently present with hand or facial dermatitis.¹

UV light therapies including narrowband UVB (NB-UVB), UVA1, and psoralen plus UVA (PUVA) have all been used as effective treatments of AD.^3,4 UV light is beneficial for AD patients due to its immunomodulatory effects, thickening of the stratum corneum, and the reduction of Staphylococcus aureus in the skin.² Most patients with AD improve with light therapy; however, it is estimated that 1% to 3% of patients with AD will experience a paradoxical worsening of their AD after exposure to UV light.^2,5 This condition is referred to as photosensitive AD and is characterized by a photodistributed rash in patients who fulfill the criteria of AD. Photosensitive AD has a female predominance and generally affects patients with late-onset disease with development of AD after puberty.^2,5 The pathogenesis for the development of photosensitivity in patients with AD who previously tolerated exposure to sunlight is unknown.⁵ We describe a case of photosensitive AD exacerbated by UVB exposure.

Case Report

A 55-year-old Asian woman presented for evaluation of a rash on the head, neck, and arms. She reported that she had developed a pruritic rash with edema after sun exposure at 16 years of age. Since then, the rash has been intermittent and completely resolved at times with periods of decreased sun exposure; however, the rash recently had been persistent and worsening despite practicing strict sun protection with daily sunscreen application, protective clothing, and sun avoidance. She was not taking systemic medications or supplements at the time but was applying high-potency topical corticosteroids and calcineurin inhibitors with minimal improvement under the care of a dermatologist.

On physical examination the patient had thin, well-demarcated, erythematous papules and plaques with scaling, primarily on sun-exposed skin on the forehead (Figure 1A), cheeks (Figure 1B), eyelids, upper lip, neck (Figures 1B and 1C), upper chest (Figure 1C), and dorsal aspect of the hands, with excoriated pink papules on the forearms, shoulders, and back. A punch biopsy of the right neck showed spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate (Figure 2). Further workup was pursued including complete blood cell count, comprehensive metabolic profile, liver function panel, Sjögren syndrome antigen A/Sjögren syndrome antigen B test, antinuclear antibody test, human immunodeficiency virus 1/2 antigen/antibody test, hepatitis panel, and mycobacterium tuberculosis test, which were all within reference range. Photodermatosis was suspected and she underwent phototesting including UVA, NB-UVB, and visible light. Phototesting confirmed she had a UVB photosensitivity with a markedly decreased minimal erythema dose (MED) to NB-UVB. The MED to NB-UVB was positive at 24 hours to all tested sites, the lowest of which was 0.135 J/cm². Eczematous changes began to develop at day 6 at doses of 0.945 and 1.080 J/cm². The patient also underwent visible light testing, which was negative. The patient was patch tested for multiple standardized agents as well as personal products, all of which were negative. Subsequent photopatch testing revealed a slightly positive reaction to benzophenone 4, a common ingredient in sunscreens.

The patient was then started on mycophenolate mofetil and prednisone. Repeat MED testing to NB-UVB was performed. Her repeat MED to NB-UVB was determined to be 0.405 J/cm², and hardening commenced at 3 times per week at 70% of the MED (0.2835 J/cm²). She began to flare and develop an eczematous reaction, thus the dose was decreased to 50% of the MED (0.2025 J/cm²), which she tolerated.

Comment

Classification and Clinical Presentation
The literature on photosensitive AD is scant, and this disease entity is rare. Alternative names include photoaggravated AD, photosensitive eczema, and light-exacerbated eczema.⁵ Two main studies have been conducted in recent years that were intended to characterize photosensitive AD. ten Berge et al⁵ conducted a retrospective study of 145 patients with AD that were phototested in 2009. They found that 3% of their total AD patient population had photosensitive AD.⁵ In 2016, Ellenbogen et al² performed a similar single-center retrospective analysis of 17 patients with long-standing AD who suddenly developed photosensitivity.

Patients with photosensitive AD typically present with lesions on sun-exposed skin with coexisting eczematous lesions in sites with a predilection for AD.² In the study conducted by ten Berge et al,⁵ 2 main reaction patterns were observed: erythematous papules with pruritus and an eczematous reaction. The authors suggested one subset of patients demonstrated polymorphous light eruption (PMLE), a common photoinduced eruption thought to represent a delayed-type hypersensitivity, coexisting with AD while the other subset had true photosensitive AD.^5,6 Ellenbogen et al² also found 2 reaction patterns, which they labeled papular (PMLE type) and eczematous (photosensitive AD type). The authors contested the theory of coexisting PMLE in AD because PMLE gets better in the summer with UV radiation hardening.² On the contrary, photosensitive AD worsens with uncontrolled exposure to sunlight. Only with controlled exposure to small doses of UV radiation at a time does this condition improve. Ellenbogen et al² believe both reaction patterns are consistent with photosensitive AD and the PMLE type should be termed papular photosensitive AD type.

Histopathology
The histopathologic findings of photosensitive AD are nonspecific but are characterized by spongiotic dermatitis with a perivascular lymphohistiocytic infiltrate.²

Diagnosis With Phototesting
Phototesting of patients with AD should be considered if there is a suspicion for photosensitivity based on persistent disease despite use of photoprotection and local treatment.^5-7 Patients may not notice a correlation of skin exacerbations with UV exposure, especially if they are only sensitive to UVA, as it is still present on cloudy days and can penetrate glass windows.⁸ Phototesting evaluates the degree of sensitivity to UV light and the specific wavelength eliciting the cutaneous response. Phototesting consists of determining the MED to UVA and UVB, the minimal phototoxic dose for PUVA, and visible light exposure. Further evaluation may include photoprovocation testing or photopatch testing, as these patients can have coexisting photocontact allergies.

The MED is defined as the minimal dose of UV light needed to induce perceptible erythema in exposed skin.⁵ It is dependent on the light source and patient’s skin type, and individual units may vary. To determine the MED to UVA or UVB, 2×2-cm skin fields are irradiated with increasing cumulative UVA/UVB. The dose varies by skin type and it is then read at 24 hours. The majority of patients with photosensitive AD are reported to have a normal MED; however, some studies have reported the MED to be decreased.^5,7-9 ten Berge et al⁵ found 7% of their study participants exhibited a lower MED, as seen in our patient.

The minimal phototoxic dose for PUVA is defined as the least exposure dose of UVA 1 hour after ingestion of 0.4 mg/kg of methoxsalen that produces pink erythema with 4 distinct borders at 48, 72, or 96 hours after ingestion.¹⁰ Visible light exposure is tested using a slide projector as the light source to an approximately 10×5-cm area of skin for 45 minutes. Any immediate or delayed reaction is abnormal and considered positive.¹⁰

Photoprovocation testing has been performed in several studies.^2,5 It consists of exposing an 8-cm area of skin to 80 J/cm² UVA and 10 mJ/cm² UVB, which is read at 24, 48, or 72 hours. A papular or eczematous reaction is considered positive.^2,11

The results of phototesting have varied between studies. ten Berge et al⁵ phototested 107 patients with AD and photosensitivity and 17% were found to be solely sensitive to UVA whereas 67% were found to be sensitive to UVA and UVB. In contrast, Ellenbogen et al² only tested 17 patients with AD and photosensitivity and they found that 56% (9/16) were sensitive to UVA alone while only 44% (7/16) were sensitive to UVA and UVB.

Photopatch testing can help to rule out photosensitivity due to a substance in the presence of UV light. In studies of patients with photosensitive AD (N=125), photocontact reactions occurred in 23% and were predominantly associated with sunscreens, skin care products, and fragrances.^5,12 Photopatch testing is done by placing duplicate sets of patches on nonlesional skin using the Finn Chamber technique. A published list of allergens, which were agreed upon by the European Society of Contact Dermatitis and the European Society for Photodermatology in 2000 are seen in Table 1.¹³ The list contains mainly UV filters and drugs. The patients’ own products also should be tested in addition to the published list of allergens, but a maximum of 30 patches should be placed at one time. The patches are removed at either 24 or 48 hours; some researchers have found greater sensitivity with the 48-hour time period, while others have not found a significant difference.¹⁰ One set of skin fields then is covered with an impermeable occlusive dressing as a control while the other is irradiated with 5 J/cm² of a broad-spectrum UVA light source. UVA fluorescent lamps are the light source of choice because of their widespread availability, reproducible broad spectrum, and beam uniformity.¹⁰ In the study conducted by ten Berge et al,⁵ photopatch testing was performed on 125 patients, and 29 patients were found to be positive to one or more substances. Ellenbogen et al² photopatch tested 5 patients with photosensitive AD and a clinical suspicion of photoallergy; however, all 5 were negative. Our patient underwent traditional patch testing due to clinical suspicion of a coexisting contact allergy, which was negative.

Conclusion

Photosensitive AD is a rare entity characterized by a photodistributed rash and involvement of non–sun-exposed skin. Patients will either have a history of AD or fulfill the criteria of AD. They have positive photoprovocation testing and generally have a normal MED. They may have positive photopatch testing with coexisting photoallergies. Histopathology is nonspecific but shows spongiotic dermatitis with perivascular lymphohistiocytic infiltrate. Diagnosis is essential, as this disease can be life altering and affect quality of life. Effective treatment options are available, and the therapeutic ladder is based on severity of disease.^2,5

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

The world in pediatric dermatology has changed in incredible ways since 1967. In fact, pediatric dermatology was not an organized specialty until years later! This article will look back at some of the history of pediatric dermatology, exploring how different the field was 50 years ago, and how it has evolved into the vibrant field that it is. By looking at some disease states, and differences in practice in relation to the care of dermatologic conditions in children both by pediatricians and dermatologists, we can see the tremendous evolution in our understanding and management of pediatric skin conditions, and perhaps gain insight into the future.

Pediatric dermatology was fairly “neonatal” 50 years ago, with only a few practitioners in the field. Recognizing that up to 30% of pediatric primary care visits include a skin-related problem, and that there was limited training about skin diseases among primary care practitioners and inconsistent training amongst dermatologists, there was a clinical need for establishing the subspecialty of pediatric dermatology. The first international symposium was held in Mexico City in October 1972, and with this meeting the International Society of Pediatric Dermatology was founded. The Society for Pediatric Dermatology (SPD) began in 1973, with Alvin Jacobs, MD, Samuel Weinberg, MD, Nancy Esterly, MD, Sidney Hurwitz, MD, William Weston, MD, and Coleman Jacobson, MD, as some of the initial “founding mothers and fathers.” The journal Pediatric Dermatology released its first issue in 1982 (35 years ago), and the American Academy of Pediatrics did not have a section of dermatology until 1986.

Lori Farmer/Frontline Medical News

Pediatrics and dermatology: The interface

Many of the first generation of pediatric dermatologists trained as pediatricians prior to pursuing their dermatology work, with some being “assigned” dermatology as pediatric experts, while others did formal residencies in dermatology. This history is important, as pediatric dermatology was, and remains, integrated with pediatrics, even while training in dermatology residencies became standard practice. An important part of the development of the field has been the education of pediatricians and dermatologists by pediatric dermatologists, with a strong sensibility that improved training for both generalists and specialists about pediatric skin disease would yield better care for patients and families.

Initially, there were very few pediatric or dermatology programs in the United States that had pediatric dermatologists. Over the succeeding decades, this is now less common, although even now there are still dermatology and pediatric residency programs that do not have a pediatric dermatologist for either training or to serve their patients. The founding leaders of the SPD set a tone of collaboration nationally and internationally, reaching out to pediatric colleagues and dermatology associates from around the world, and establishing superb educational programs for the exchange of ideas, presentation of challenging cases, and promoting state of the art knowledge of the field. Through annual meetings of the SPD, conferences immediately preceding the American Academy of Dermatology annual meetings, the World Congress of Pediatric Dermatology, and other regional and international meetings, the field developed as the number of practitioners grew, and as the specialized published literature reflected new knowledge in diagnosis and therapy.

LucaLorenzelli/Thinkstock

Examples of changing perspectives: hemangiomas

A good way to look at evolution of the field is take a look at some of the similarities and differences in clinical practice in relation to common and uncommon disease states.

A great example is hemangiomas. Some of the first natural history studies on hemangiomas were done in the early 1960s, establishing that many lesions had a typical clinical course of fairly rapid growth, plateau, and involution over time. Of course, the identification of hemangiomas of infancy (or “HOI” in the trade), was confused with vascular malformations, and no one had recognized variant tumors that were distinct, such as rapidly involuting and noninvoluting congenital hemangiomas (RICHs or NICHs), tufted angiomas, and hemangioendotheliomas. PHACE syndrome (posterior fossa brain malformations) had yet to be described (that was done in 1996 by Ilona Frieden and her colleagues). For a time period, hemangiomas were treated with X-rays, before the negative impact of such radiation was acknowledged. For many years after that, even deforming and functionally significant lesions were “followed clinically” for natural involution, presumably a backlash from the radiation therapy interventions.

Courtesy of RegionalDerm.com

Procedural pediatric dermatology: Tremendous revolution in surgery and laser

The first generation of pediatric dermatologists were considered medical dermatologist specialists. And how important this specialty work was! Acne, atopic dermatitis, psoriasis, diaper and seborrheic dermatitis, and rare genetic syndromes, these conditions were a major part of the work of early pediatric dermatologists (and remain so now). What was not common was for pediatric dermatologists to have procedural or surgical practices, while this now is routinely part of the work of specialists in the field. How did this shift occur?

The fundamental shift began to occur with the introduction of the pulsed dye laser in 1989 and the publication of a seminal article in the New England Journal of Medicine (1989 Feb 16;320[7]:416-21) on its utility in treating port-wine stains in children with minimal scarring. Vascular lesions including port-wine stains were common, and pediatric dermatologists managed these patients for both diagnosis and medical management. Also, dermatology residencies at this time offered training in cutaneous surgery, excisions (including Mohs surgery) and repairs, and trainees in pediatric dermatology were “trained up” to high levels of expertise. As lasers were incorporated into dermatology residency work and practices, pediatric dermatologists had the exposure and skill to do this work. An added advantage was having the pediatric knowledge of how to handle children and adolescents in an age appropriate manner, and consideration of methods to minimize the pain and anxiety of procedures. Within a few years, pediatric dermatologists were at the forefront of the use of topical anesthetics (EMLA and liposomal lidocaine) and had general anesthesia privileges for laser and excisional surgery.

So while pediatric dermatologists still do “small procedures” every hour in most practices (cryotherapy for warts, cantharidin for molluscum, shave and punch biopsies), a subset now have extensive procedural practices, which in recent years has extended to pigment lesion lasers (to treat nevus of Ota), hair lasers (to treat perineal areas to prevent pilonidal cyst recurrence or to treat hirsutism), and combinations of lasers to treat hypertrophic, constrictive, and/or deforming scars).

Inflammatory skin disorders: Bread and butter ... and peanut butter?

The care of pediatric inflammatory skin disorders has evolved, but more slowly for some diseases than others. Acne vulgaris now is recognized as much more common under age 12 years than previously, presumably reflecting earlier pubertal changes in our preteens. Over the past 30 years, therapy has evolved with the use of topical retinoids (still underused by pediatricians, considered a “practice gap”), hormonal therapy with combined oral contraceptives, and oral isotretinoin, a powerful but highly effective systemic agent for severe and refractory acne. Specific pediatric guidelines came much later. Pediatric acne expert recommendations were formulated by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013 (Pediatrics. 2013;131:S163-86). Over the past few years, there is a push by experts for more judicious use of antibiotics for acne (oral and topical) to minimize the emergence of bacterial resistance.

Psoriasis has been a condition that has been “behind the revolution,” in that no biologic agent was approved for pediatric psoriasis in the United States until several months ago, lagging behind Europe and elsewhere in the world by almost a decade. Adult psoriasis has been recognized to be associated with a broad set of comorbidities, including obesity and early heart disease, and there is now research on how children are at risk as well, and new recommendations on how to screen children with psoriasis. Moderate to severe psoriasis in adults is now tremendously controllable with biologic agents targeting TNF-alpha, IL 12/23, and IL-17. Etanercept has been approved for children with psoriasis aged 4 years and older, and other biologic agents are under study.

Atopic dermatitis now is ready for its revolution! AD has increased in prevalence from around 5% of the pediatric population 30-plus years ago to 10%-15%. Treatment of most individuals has remained the same over the decades: Good skin care, frequent moisturizers, topical corticosteroids for flares, management of infection if noted. The topical calcineurin inhibitors (TCIs) broadened the therapeutic approach when introduced in 2000 and 2001, but the boxed warning resulted in some practitioners minimizing their utilization of these useful agents.

The future

Where will pediatric skin disease, or more importantly, skin health over a lifetime be in 50 years? Can we cure or prevent the consequences of our lethal and life altering genetic diseases such as epidermolysis bullosa or our neurocutaneous disorders? Will our new insights into birthmarks (they are mostly somatic mutations) allow us to form specific, personalized therapies to minimize their impact? Will we be using computers equipped with imaging devices and algorithms to assess our patients’ moles, papules, and nodules? Will our vaccines have wiped out warts, molluscum, and perhaps, acne? Will we have cured our inflammatory skin disorders, or perhaps prevented them by interventions in the neonatal period? No predictions will be offered here, other than that we can look forward to incredible changes for our future generations of health care practitioners, patients, and families.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego and professor of dermatology and pediatrics at the University of California, San Diego. Dr. Eichenfield has served as a consultant for Anacor/Pfizer and Regeneron/Sanofi. Email him at pdnews@frontlinemedcom.com.

This article exhibits key pediatric dermatology pearls garnered at the 2017 Annual Meeting of the American Academy of Dermatology (AAD) in Orlando, Florida (March 3–7, 2017). Highlights from both the Society for Pediatric Dermatology pre-AAD meeting (March 2, 2017) and the AAD general meeting sessions are included. This discussion is intended to help maximize care of our pediatric patients in dermatology and present high-yield take-home points from the AAD that can be readily transferred to our patient care.

“New Tools for Your Therapeutic Toolbox” by Erin Mathes, MD (University of California, San Francisco)

During this lecture at the Society for Pediatric Dermatology meeting, Dr. Mathes discussed a randomized controlled trial that took place in 2014 in both the United States and the United Kingdom to assess skin barrier enhancement to reduce the incidence of atopic dermatitis (AD) in 124 high-risk infants.¹ The high-risk infants had either a parent or sibling with physician-diagnosed AD, asthma, or rhinitis, or a first-degree relative with an aforementioned condition. Full-body emollient therapy was applied at least once daily within 3 weeks of birth for 6 months, while the control arm did not use emollient. Parents were allowed to choose from the following emollients: sunflower seed oil, moisturizing cream, or ointment. The primary outcome was the incidence of AD at 6 months. The authors found a 43% incidence of AD in the control group compared to 22% in the emollient group, amounting to a relative risk reduction of approximately 50%.¹

Emollients in AD are hypothesized to help through the enhanced barrier function and decreased penetration of irritant substances and allergens. This study is vital given the ease of use of emollients and the foreseeable substantial impact on reduced health care costs associated with the decreased incidence of AD.

Take-Home Point
Full-body emollient therapy within 3 weeks of birth may reduce the incidence of AD in high-risk infants.

Dr. Mathes also discussed the novel topical phosphodiesterase 4 inhibitor crisaborole and its emerging role in AD. She reviewed the results of a large phase 3 trial of crisaborole therapy for patients aged 2 years or older with mild to moderate AD.² Crisaborole ointment was applied twice daily for 28 days. The primary outcome measured was an investigator static global assessment score of clear or almost clear, which is a score for AD based on the degree of erythema, presence of oozing and crusting, and presence of induration or papulation. Overall, 32.8% of patients treated with crisaborole achieved success compared to 25.4% of vehicle-treated patients. The control patients were still given a vehicle to apply, which can function as therapy to help repair the barrier of AD and thus theoretically reduced the percentage gap between patients who met success with and without crisaborole therapy. Furthermore, only 4% of patients reported adverse effects such as burning and stinging with application of crisaborole in contrast to topical calcineurin inhibitors, which can elicit symptoms up to 50% of the time.² In summary, this lecture reviewed the first new topical treatment for AD in 15 years.

Take-Home Point
Crisaborole ointment is a novel topical phosphodiesterase 4 inhibitor approved for mild to moderate AD in patients 2 years of age and older.

“The Truth About Pediatric Contact Dermatitis” by Sharon Jacob, MD (Loma Linda University, California)

In this session, Dr. Jacob discussed how she approaches pediatric patients with suspected contact dermatitis and elaborated on the common allergens unique to this patient population. Furthermore, she explained the substantial role of nickel in pediatric contact dermatitis, citing a study performed in Denmark and the United States, which tested 212 toys for nickel using the dimethylglyoxime test and found that 34.4% of toys did in fact release nickel.³ Additional studies have shown that nickel released from children’s toys is deposited on the skin, even with short contact times such as 30 minutes on one or more occasions within 2 weeks.^3,4 She is currently evaluating the presence of nickel in locales frequented by children such as schools, libraries, and supermarkets. Interestingly, she anecdotally found that a pediatric eczematous eruption in a spiralized distribution of the legs can be attributed to the presence of nickel in school chairs, and the morphology is secondary to children wrapping their legs around the chairs. In conclusion, she reiterated that nickel continues to be the top allergen among pediatric patients, and states that additional allergens for patch testing in this population are unique to their adult counterparts.

Take-Home Point
Nickel is an ubiquitous allergen for pediatric contact dermatitis; additionally, the list of allergens for patch testing should be tailored to this patient population.

“When to Image, When to Sedate” by Annette Wagner, MD (Northwestern Medicine, Chicago, Illinois)

This lecture was a 3-part discussion on the safety of general anesthesia in children, when to image children, and when sedation may be worth the risk. Dr. Wagner shared her pearls for when children younger than 3 years may benefit from dermatologic procedures that involve general anesthesia. Large congenital lesions of the scalp or face that require tissue expansion or multiple stages may be best performed at a younger age due to the flexibility of the infant scalp, providing the best outcome. Additional considerations include a questionable malignant diagnosis in which a punch biopsy is not enough, rapidly growing facial lesions, Spitz nevi of the face, congenital lesions with no available therapy, and nonhealing refractory lesions causing severe pain. The general rule proposed was intervention for single procedures lasting less than 1 hour that otherwise would result in a worse outcome if postponed. Finally, she concluded to always advocate for your patient, to wait if the outcome will be the same regardless of timing, and to be frank about not knowing the risks of general anesthesia in this population. The resource, SmartTots (http://smarttots.org) provides current consensus statements and ongoing research on the use and safety of general anesthesia in children.

Take-Home Point
General sedation may be considered for short pediatric procedures that will result in a worse outcome if postponed.

“Highlights From the Pediatric Literature” by Katherine Marks, DO (Geisinger, Danville and Wilkes-Barre, Pennsylvania)

Dr. Marks discussed numerous emerging pediatric dermatology articles. One article looked at 40 infants with proliferating infantile hemangiomas (IHs) who had timolol gel 0.5% applied twice daily.⁵ The primary outcomes were the urinary excretion and serum levels of timolol as well as the clinical response to therapy measured by a visual analog scale at monthly visits. A urinalysis collected 3 to 4 hours after timolol application was found to be positive in 83% (20/24) of the tested patients; the first 3 positive infants were then sent to have their serum timolol levels drawn and also were found to be positive, though substantially small levels (median, 0.16 ng/mL). The 3 patients tested had small IHs on the face with no ulceration. None of these patients experienced adverse effects and all of the IHs significantly (P<.001) improved with therapy. The authors stated that even though the absorption was minimal, it is wise to be cognizant about the use of timolol in certain patient demographics such as preterm or young infants with large ulcerating IHs.⁵

Take-Home Point
Systemic absorption with topical timolol occurs, albeit substantially small; be judicious about giving this medication in select patient populations with ulcerated hemangiomas.

Acknowledgment
The author thanks the presenters for their review and contributions to this article.

This article exhibits key pediatric dermatology pearls garnered at the 2017 Annual Meeting of the American Academy of Dermatology (AAD) in Orlando, Florida (March 3–7, 2017). Highlights from both the Society for Pediatric Dermatology pre-AAD meeting (March 2, 2017) and the AAD general meeting sessions are included. This discussion is intended to help maximize care of our pediatric patients in dermatology and present high-yield take-home points from the AAD that can be readily transferred to our patient care.

“New Tools for Your Therapeutic Toolbox” by Erin Mathes, MD (University of California, San Francisco)

During this lecture at the Society for Pediatric Dermatology meeting, Dr. Mathes discussed a randomized controlled trial that took place in 2014 in both the United States and the United Kingdom to assess skin barrier enhancement to reduce the incidence of atopic dermatitis (AD) in 124 high-risk infants.¹ The high-risk infants had either a parent or sibling with physician-diagnosed AD, asthma, or rhinitis, or a first-degree relative with an aforementioned condition. Full-body emollient therapy was applied at least once daily within 3 weeks of birth for 6 months, while the control arm did not use emollient. Parents were allowed to choose from the following emollients: sunflower seed oil, moisturizing cream, or ointment. The primary outcome was the incidence of AD at 6 months. The authors found a 43% incidence of AD in the control group compared to 22% in the emollient group, amounting to a relative risk reduction of approximately 50%.¹

Emollients in AD are hypothesized to help through the enhanced barrier function and decreased penetration of irritant substances and allergens. This study is vital given the ease of use of emollients and the foreseeable substantial impact on reduced health care costs associated with the decreased incidence of AD.

Take-Home Point
Full-body emollient therapy within 3 weeks of birth may reduce the incidence of AD in high-risk infants.

Dr. Mathes also discussed the novel topical phosphodiesterase 4 inhibitor crisaborole and its emerging role in AD. She reviewed the results of a large phase 3 trial of crisaborole therapy for patients aged 2 years or older with mild to moderate AD.² Crisaborole ointment was applied twice daily for 28 days. The primary outcome measured was an investigator static global assessment score of clear or almost clear, which is a score for AD based on the degree of erythema, presence of oozing and crusting, and presence of induration or papulation. Overall, 32.8% of patients treated with crisaborole achieved success compared to 25.4% of vehicle-treated patients. The control patients were still given a vehicle to apply, which can function as therapy to help repair the barrier of AD and thus theoretically reduced the percentage gap between patients who met success with and without crisaborole therapy. Furthermore, only 4% of patients reported adverse effects such as burning and stinging with application of crisaborole in contrast to topical calcineurin inhibitors, which can elicit symptoms up to 50% of the time.² In summary, this lecture reviewed the first new topical treatment for AD in 15 years.

Take-Home Point
Crisaborole ointment is a novel topical phosphodiesterase 4 inhibitor approved for mild to moderate AD in patients 2 years of age and older.

“The Truth About Pediatric Contact Dermatitis” by Sharon Jacob, MD (Loma Linda University, California)

In this session, Dr. Jacob discussed how she approaches pediatric patients with suspected contact dermatitis and elaborated on the common allergens unique to this patient population. Furthermore, she explained the substantial role of nickel in pediatric contact dermatitis, citing a study performed in Denmark and the United States, which tested 212 toys for nickel using the dimethylglyoxime test and found that 34.4% of toys did in fact release nickel.³ Additional studies have shown that nickel released from children’s toys is deposited on the skin, even with short contact times such as 30 minutes on one or more occasions within 2 weeks.^3,4 She is currently evaluating the presence of nickel in locales frequented by children such as schools, libraries, and supermarkets. Interestingly, she anecdotally found that a pediatric eczematous eruption in a spiralized distribution of the legs can be attributed to the presence of nickel in school chairs, and the morphology is secondary to children wrapping their legs around the chairs. In conclusion, she reiterated that nickel continues to be the top allergen among pediatric patients, and states that additional allergens for patch testing in this population are unique to their adult counterparts.

Take-Home Point
Nickel is an ubiquitous allergen for pediatric contact dermatitis; additionally, the list of allergens for patch testing should be tailored to this patient population.

“When to Image, When to Sedate” by Annette Wagner, MD (Northwestern Medicine, Chicago, Illinois)

This lecture was a 3-part discussion on the safety of general anesthesia in children, when to image children, and when sedation may be worth the risk. Dr. Wagner shared her pearls for when children younger than 3 years may benefit from dermatologic procedures that involve general anesthesia. Large congenital lesions of the scalp or face that require tissue expansion or multiple stages may be best performed at a younger age due to the flexibility of the infant scalp, providing the best outcome. Additional considerations include a questionable malignant diagnosis in which a punch biopsy is not enough, rapidly growing facial lesions, Spitz nevi of the face, congenital lesions with no available therapy, and nonhealing refractory lesions causing severe pain. The general rule proposed was intervention for single procedures lasting less than 1 hour that otherwise would result in a worse outcome if postponed. Finally, she concluded to always advocate for your patient, to wait if the outcome will be the same regardless of timing, and to be frank about not knowing the risks of general anesthesia in this population. The resource, SmartTots (http://smarttots.org) provides current consensus statements and ongoing research on the use and safety of general anesthesia in children.

Take-Home Point
General sedation may be considered for short pediatric procedures that will result in a worse outcome if postponed.

“Highlights From the Pediatric Literature” by Katherine Marks, DO (Geisinger, Danville and Wilkes-Barre, Pennsylvania)

Dr. Marks discussed numerous emerging pediatric dermatology articles. One article looked at 40 infants with proliferating infantile hemangiomas (IHs) who had timolol gel 0.5% applied twice daily.⁵ The primary outcomes were the urinary excretion and serum levels of timolol as well as the clinical response to therapy measured by a visual analog scale at monthly visits. A urinalysis collected 3 to 4 hours after timolol application was found to be positive in 83% (20/24) of the tested patients; the first 3 positive infants were then sent to have their serum timolol levels drawn and also were found to be positive, though substantially small levels (median, 0.16 ng/mL). The 3 patients tested had small IHs on the face with no ulceration. None of these patients experienced adverse effects and all of the IHs significantly (P<.001) improved with therapy. The authors stated that even though the absorption was minimal, it is wise to be cognizant about the use of timolol in certain patient demographics such as preterm or young infants with large ulcerating IHs.⁵

Take-Home Point
Systemic absorption with topical timolol occurs, albeit substantially small; be judicious about giving this medication in select patient populations with ulcerated hemangiomas.

Acknowledgment
The author thanks the presenters for their review and contributions to this article.

This article exhibits key pediatric dermatology pearls garnered at the 2017 Annual Meeting of the American Academy of Dermatology (AAD) in Orlando, Florida (March 3–7, 2017). Highlights from both the Society for Pediatric Dermatology pre-AAD meeting (March 2, 2017) and the AAD general meeting sessions are included. This discussion is intended to help maximize care of our pediatric patients in dermatology and present high-yield take-home points from the AAD that can be readily transferred to our patient care.

“New Tools for Your Therapeutic Toolbox” by Erin Mathes, MD (University of California, San Francisco)

During this lecture at the Society for Pediatric Dermatology meeting, Dr. Mathes discussed a randomized controlled trial that took place in 2014 in both the United States and the United Kingdom to assess skin barrier enhancement to reduce the incidence of atopic dermatitis (AD) in 124 high-risk infants.¹ The high-risk infants had either a parent or sibling with physician-diagnosed AD, asthma, or rhinitis, or a first-degree relative with an aforementioned condition. Full-body emollient therapy was applied at least once daily within 3 weeks of birth for 6 months, while the control arm did not use emollient. Parents were allowed to choose from the following emollients: sunflower seed oil, moisturizing cream, or ointment. The primary outcome was the incidence of AD at 6 months. The authors found a 43% incidence of AD in the control group compared to 22% in the emollient group, amounting to a relative risk reduction of approximately 50%.¹

Emollients in AD are hypothesized to help through the enhanced barrier function and decreased penetration of irritant substances and allergens. This study is vital given the ease of use of emollients and the foreseeable substantial impact on reduced health care costs associated with the decreased incidence of AD.

Take-Home Point
Full-body emollient therapy within 3 weeks of birth may reduce the incidence of AD in high-risk infants.

Dr. Mathes also discussed the novel topical phosphodiesterase 4 inhibitor crisaborole and its emerging role in AD. She reviewed the results of a large phase 3 trial of crisaborole therapy for patients aged 2 years or older with mild to moderate AD.² Crisaborole ointment was applied twice daily for 28 days. The primary outcome measured was an investigator static global assessment score of clear or almost clear, which is a score for AD based on the degree of erythema, presence of oozing and crusting, and presence of induration or papulation. Overall, 32.8% of patients treated with crisaborole achieved success compared to 25.4% of vehicle-treated patients. The control patients were still given a vehicle to apply, which can function as therapy to help repair the barrier of AD and thus theoretically reduced the percentage gap between patients who met success with and without crisaborole therapy. Furthermore, only 4% of patients reported adverse effects such as burning and stinging with application of crisaborole in contrast to topical calcineurin inhibitors, which can elicit symptoms up to 50% of the time.² In summary, this lecture reviewed the first new topical treatment for AD in 15 years.

Take-Home Point
Crisaborole ointment is a novel topical phosphodiesterase 4 inhibitor approved for mild to moderate AD in patients 2 years of age and older.

“The Truth About Pediatric Contact Dermatitis” by Sharon Jacob, MD (Loma Linda University, California)

In this session, Dr. Jacob discussed how she approaches pediatric patients with suspected contact dermatitis and elaborated on the common allergens unique to this patient population. Furthermore, she explained the substantial role of nickel in pediatric contact dermatitis, citing a study performed in Denmark and the United States, which tested 212 toys for nickel using the dimethylglyoxime test and found that 34.4% of toys did in fact release nickel.³ Additional studies have shown that nickel released from children’s toys is deposited on the skin, even with short contact times such as 30 minutes on one or more occasions within 2 weeks.^3,4 She is currently evaluating the presence of nickel in locales frequented by children such as schools, libraries, and supermarkets. Interestingly, she anecdotally found that a pediatric eczematous eruption in a spiralized distribution of the legs can be attributed to the presence of nickel in school chairs, and the morphology is secondary to children wrapping their legs around the chairs. In conclusion, she reiterated that nickel continues to be the top allergen among pediatric patients, and states that additional allergens for patch testing in this population are unique to their adult counterparts.

Take-Home Point
Nickel is an ubiquitous allergen for pediatric contact dermatitis; additionally, the list of allergens for patch testing should be tailored to this patient population.

“When to Image, When to Sedate” by Annette Wagner, MD (Northwestern Medicine, Chicago, Illinois)

This lecture was a 3-part discussion on the safety of general anesthesia in children, when to image children, and when sedation may be worth the risk. Dr. Wagner shared her pearls for when children younger than 3 years may benefit from dermatologic procedures that involve general anesthesia. Large congenital lesions of the scalp or face that require tissue expansion or multiple stages may be best performed at a younger age due to the flexibility of the infant scalp, providing the best outcome. Additional considerations include a questionable malignant diagnosis in which a punch biopsy is not enough, rapidly growing facial lesions, Spitz nevi of the face, congenital lesions with no available therapy, and nonhealing refractory lesions causing severe pain. The general rule proposed was intervention for single procedures lasting less than 1 hour that otherwise would result in a worse outcome if postponed. Finally, she concluded to always advocate for your patient, to wait if the outcome will be the same regardless of timing, and to be frank about not knowing the risks of general anesthesia in this population. The resource, SmartTots (http://smarttots.org) provides current consensus statements and ongoing research on the use and safety of general anesthesia in children.

Take-Home Point
General sedation may be considered for short pediatric procedures that will result in a worse outcome if postponed.

“Highlights From the Pediatric Literature” by Katherine Marks, DO (Geisinger, Danville and Wilkes-Barre, Pennsylvania)

Dr. Marks discussed numerous emerging pediatric dermatology articles. One article looked at 40 infants with proliferating infantile hemangiomas (IHs) who had timolol gel 0.5% applied twice daily.⁵ The primary outcomes were the urinary excretion and serum levels of timolol as well as the clinical response to therapy measured by a visual analog scale at monthly visits. A urinalysis collected 3 to 4 hours after timolol application was found to be positive in 83% (20/24) of the tested patients; the first 3 positive infants were then sent to have their serum timolol levels drawn and also were found to be positive, though substantially small levels (median, 0.16 ng/mL). The 3 patients tested had small IHs on the face with no ulceration. None of these patients experienced adverse effects and all of the IHs significantly (P<.001) improved with therapy. The authors stated that even though the absorption was minimal, it is wise to be cognizant about the use of timolol in certain patient demographics such as preterm or young infants with large ulcerating IHs.⁵

Take-Home Point
Systemic absorption with topical timolol occurs, albeit substantially small; be judicious about giving this medication in select patient populations with ulcerated hemangiomas.

Acknowledgment
The author thanks the presenters for their review and contributions to this article.