Atopic Dermatitis

KYOTO, JAPAN — Atopic dermatitis is one of the most common skin diseases in Japanese adults, especially those in their 20s and 30s, according to a first-of-its-kind study.

The high prevalence rates found were quite similar to those earlier reported in an Australian study in which, as in the Japanese study, the diagnosis of adult atopic dermatitis was made by experienced dermatologists. Taken together, these two large studies suggest atopic dermatitis in adults is common and underappreciated, according to Dr. Hidehisa Saeki, a dermatologist at the University of Tokyo.

He reported on 2,943 staff members, aged 20–69, at two Japanese medical schools. When they reported for their required annual general health checkup, they were examined by dermatologists who diagnosed atopic dermatitis using Japanese Dermatological Association criteria, which are similar to Hanifin criteria.

This was the first study of adult atopic dermatitis in Japan in which the diagnosis was based upon clinical examination by dermatologists, Dr. Saeki reported at an international investigative dermatology meeting.

The prevalence of atopic dermatitis was 8% in 1,184 women and 5% in 1,759 men. The disease was classified as mild in 79% of cases, moderate in 17%, severe in 3%, and very severe—meaning greater than 30% skin area involvement during eruptions—in 1%.

The overall prevalence of atopic dermatitis was 9% among subjects in their 20s, 8% in the 30s, 5% in the 40s, and 3% in participants in their 50s and 60s.

Most affected adults had a history of atopic dermatitis in childhood, Dr. Saeki explained at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Worldwide, there have been few studies of atopic dermatitis in adults, and mostly they relied upon questionnaire surveys. One of the rare exceptions that employed total body examination and dermatologic diagnosis was conducted by investigators at the University of Melbourne, who reported a 7% prevalence of atopic dermatitis—quite close to the Japanese figure—in 1,457 residents of central Victoria aged 20–94 years (Int. J. Dermatol. 1999;38:901–8).

Dr. Saeki noted that the Australian and Japanese investigators found many shared trends in adult atopic dermatitis: the prevalence in both countries was higher in women, the prevalence declined with age, and roughly 80% of affected individuals had mild disease.

American dermatologists in the audience expressed amazement at the striking cultural difference between the United States and Japan as reflected in the greater than 95% attendance rate for routine annual health checkups in Dr. Saeki's study.

"In my country it seems like nobody comes in," commented an American physician.

As with an earlier Australian study, prevalence was higher in women and declinedwith age. DR. SAEKI

KYOTO, JAPAN — Atopic dermatitis is one of the most common skin diseases in Japanese adults, especially those in their 20s and 30s, according to a first-of-its-kind study.

The high prevalence rates found were quite similar to those earlier reported in an Australian study in which, as in the Japanese study, the diagnosis of adult atopic dermatitis was made by experienced dermatologists. Taken together, these two large studies suggest atopic dermatitis in adults is common and underappreciated, according to Dr. Hidehisa Saeki, a dermatologist at the University of Tokyo.

He reported on 2,943 staff members, aged 20–69, at two Japanese medical schools. When they reported for their required annual general health checkup, they were examined by dermatologists who diagnosed atopic dermatitis using Japanese Dermatological Association criteria, which are similar to Hanifin criteria.

This was the first study of adult atopic dermatitis in Japan in which the diagnosis was based upon clinical examination by dermatologists, Dr. Saeki reported at an international investigative dermatology meeting.

The prevalence of atopic dermatitis was 8% in 1,184 women and 5% in 1,759 men. The disease was classified as mild in 79% of cases, moderate in 17%, severe in 3%, and very severe—meaning greater than 30% skin area involvement during eruptions—in 1%.

The overall prevalence of atopic dermatitis was 9% among subjects in their 20s, 8% in the 30s, 5% in the 40s, and 3% in participants in their 50s and 60s.

Most affected adults had a history of atopic dermatitis in childhood, Dr. Saeki explained at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Worldwide, there have been few studies of atopic dermatitis in adults, and mostly they relied upon questionnaire surveys. One of the rare exceptions that employed total body examination and dermatologic diagnosis was conducted by investigators at the University of Melbourne, who reported a 7% prevalence of atopic dermatitis—quite close to the Japanese figure—in 1,457 residents of central Victoria aged 20–94 years (Int. J. Dermatol. 1999;38:901–8).

Dr. Saeki noted that the Australian and Japanese investigators found many shared trends in adult atopic dermatitis: the prevalence in both countries was higher in women, the prevalence declined with age, and roughly 80% of affected individuals had mild disease.

American dermatologists in the audience expressed amazement at the striking cultural difference between the United States and Japan as reflected in the greater than 95% attendance rate for routine annual health checkups in Dr. Saeki's study.

"In my country it seems like nobody comes in," commented an American physician.

As with an earlier Australian study, prevalence was higher in women and declinedwith age. DR. SAEKI

KYOTO, JAPAN — Atopic dermatitis is one of the most common skin diseases in Japanese adults, especially those in their 20s and 30s, according to a first-of-its-kind study.

The high prevalence rates found were quite similar to those earlier reported in an Australian study in which, as in the Japanese study, the diagnosis of adult atopic dermatitis was made by experienced dermatologists. Taken together, these two large studies suggest atopic dermatitis in adults is common and underappreciated, according to Dr. Hidehisa Saeki, a dermatologist at the University of Tokyo.

He reported on 2,943 staff members, aged 20–69, at two Japanese medical schools. When they reported for their required annual general health checkup, they were examined by dermatologists who diagnosed atopic dermatitis using Japanese Dermatological Association criteria, which are similar to Hanifin criteria.

This was the first study of adult atopic dermatitis in Japan in which the diagnosis was based upon clinical examination by dermatologists, Dr. Saeki reported at an international investigative dermatology meeting.

The prevalence of atopic dermatitis was 8% in 1,184 women and 5% in 1,759 men. The disease was classified as mild in 79% of cases, moderate in 17%, severe in 3%, and very severe—meaning greater than 30% skin area involvement during eruptions—in 1%.

The overall prevalence of atopic dermatitis was 9% among subjects in their 20s, 8% in the 30s, 5% in the 40s, and 3% in participants in their 50s and 60s.

Most affected adults had a history of atopic dermatitis in childhood, Dr. Saeki explained at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Worldwide, there have been few studies of atopic dermatitis in adults, and mostly they relied upon questionnaire surveys. One of the rare exceptions that employed total body examination and dermatologic diagnosis was conducted by investigators at the University of Melbourne, who reported a 7% prevalence of atopic dermatitis—quite close to the Japanese figure—in 1,457 residents of central Victoria aged 20–94 years (Int. J. Dermatol. 1999;38:901–8).

Dr. Saeki noted that the Australian and Japanese investigators found many shared trends in adult atopic dermatitis: the prevalence in both countries was higher in women, the prevalence declined with age, and roughly 80% of affected individuals had mild disease.

American dermatologists in the audience expressed amazement at the striking cultural difference between the United States and Japan as reflected in the greater than 95% attendance rate for routine annual health checkups in Dr. Saeki's study.

"In my country it seems like nobody comes in," commented an American physician.

As with an earlier Australian study, prevalence was higher in women and declinedwith age. DR. SAEKI

KYOTO, JAPAN — The predisposition to recurrent skin infections in atopic dermatitis might be explained by the recent discovery that interleukin-17 is relatively absent in lesional skin, said Dr. Emma Guttman-Yassky.

She and her coinvestigators demonstrated that interleukin-17 (IL-17) selectively induces epidermal keratinocytes to express innate defense proteins, including the antimicrobial peptides lipocalin 2, elafin, human beta-defensin-2, cathelicidin, and psoriasin.

When IL-17 is hypoexpressed in the skin barrier, as she and her colleagues have shown is the case in atopic dermatitis, it means having less of these antimicrobial peptides on-site—and that translates into diminished innate immune defense against microbial invasion, said Dr. Guttman-Yassky of Rockefeller University, New York, at an international investigative dermatology meeting.

"IL-17 is the master regulator of innate defense protein expression in keratinocytes," she said.

Dr. Guttman-Yassky reported on a study of biopsies obtained from lesional skin of 18 atopic dermatitis patients, both lesional and nonlesional skin of 15 psoriasis patients, and skin from 15 normal controls. Specimens were analyzed by gene microarray analysis, immunohistochemistry, and polymerase chain reaction.

According to Dr. Guttman-Yassky, the key findings included the following:

▸ Both IL-23 and the IL-23 receptor are highly activated in psoriatic lesions, compared with atopic dermatitis lesions, which in turn feature higher levels than in the nonlesional skin of psoriasis patients or normal skin of controls. IL-23 is known to activate IL-23 receptor-bearing Th17 T cells and induce them to produce IL-17 and IL-22.

▸ IL-17 is highly upregulated in psoriatic lesions, compared with atopic dermatitis lesions. This is probably in large part why psoriasis is not characterized by recurrent superinfections, she noted.

▸ Expression of lipocalin 2 and other antimicrobial peptides by epidermal keratinocytes is upregulated in psoriatic skin, compared with atopic dermatitis lesions or normal skin.

▸ Administration of IL-17 to keratinocytes in vitro results in strong upregulation of the innate defense peptides. Administration of interferon-gamma does not.

These observations led the investigators to several hypotheses regarding the nature of some of the key immunologic differences between atopic dermatitis and psoriasis, the two most common inflammatory skin diseases.

One hypothesis is that the IL-23/Th17 axis figures prominently in psoriasis but is largely absent in lesional skin of atopic dermatitis. This difference is due to major differences in the nature of the epidermal and dermal inflammatory dendritic cells involved in the two diseases, and the downstream cytokine environment these dendritic cells create.

The key dendritic cells in psoriasis upregulate tumor necrosis factor-α, IL-23, and IL-12, driving T cells toward the Th1 phenotype. In contrast, the inflammatory dendritic cells in atopic dermatitis are more heavily influenced by thymic stromal lymphopoietin, driving T cells toward the Th2 phenotype, Dr. Guttman-Yassky said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience member Dr. Jon M. Hanifin called the findings intriguing. He posed the question: What effect do the very high levels of IL-10 characteristically present in atopic dermatitis lesions have on the IL-23/Th17 axis? These elevated IL-10 levels constitute a key distinction between atopic dermatitis and psoriasis that has gone almost completely overlooked to date by researchers, said Dr. Hanifin, professor of dermatology at Oregon Health and Science University, Portland.

Dr. Guttman-Yassky replied that much work remains to be done in unravelling the immunologies of these two diseases, and conceded that she and her coworkers have not included measurement of IL-10.

'IL-17 is the master regulator of innate defense protein expression in keratinocytes.' DR. GUTTMAN-YASSKY

KYOTO, JAPAN — The predisposition to recurrent skin infections in atopic dermatitis might be explained by the recent discovery that interleukin-17 is relatively absent in lesional skin, said Dr. Emma Guttman-Yassky.

She and her coinvestigators demonstrated that interleukin-17 (IL-17) selectively induces epidermal keratinocytes to express innate defense proteins, including the antimicrobial peptides lipocalin 2, elafin, human beta-defensin-2, cathelicidin, and psoriasin.

When IL-17 is hypoexpressed in the skin barrier, as she and her colleagues have shown is the case in atopic dermatitis, it means having less of these antimicrobial peptides on-site—and that translates into diminished innate immune defense against microbial invasion, said Dr. Guttman-Yassky of Rockefeller University, New York, at an international investigative dermatology meeting.

"IL-17 is the master regulator of innate defense protein expression in keratinocytes," she said.

Dr. Guttman-Yassky reported on a study of biopsies obtained from lesional skin of 18 atopic dermatitis patients, both lesional and nonlesional skin of 15 psoriasis patients, and skin from 15 normal controls. Specimens were analyzed by gene microarray analysis, immunohistochemistry, and polymerase chain reaction.

According to Dr. Guttman-Yassky, the key findings included the following:

▸ Both IL-23 and the IL-23 receptor are highly activated in psoriatic lesions, compared with atopic dermatitis lesions, which in turn feature higher levels than in the nonlesional skin of psoriasis patients or normal skin of controls. IL-23 is known to activate IL-23 receptor-bearing Th17 T cells and induce them to produce IL-17 and IL-22.

▸ IL-17 is highly upregulated in psoriatic lesions, compared with atopic dermatitis lesions. This is probably in large part why psoriasis is not characterized by recurrent superinfections, she noted.

▸ Expression of lipocalin 2 and other antimicrobial peptides by epidermal keratinocytes is upregulated in psoriatic skin, compared with atopic dermatitis lesions or normal skin.

▸ Administration of IL-17 to keratinocytes in vitro results in strong upregulation of the innate defense peptides. Administration of interferon-gamma does not.

These observations led the investigators to several hypotheses regarding the nature of some of the key immunologic differences between atopic dermatitis and psoriasis, the two most common inflammatory skin diseases.

One hypothesis is that the IL-23/Th17 axis figures prominently in psoriasis but is largely absent in lesional skin of atopic dermatitis. This difference is due to major differences in the nature of the epidermal and dermal inflammatory dendritic cells involved in the two diseases, and the downstream cytokine environment these dendritic cells create.

The key dendritic cells in psoriasis upregulate tumor necrosis factor-α, IL-23, and IL-12, driving T cells toward the Th1 phenotype. In contrast, the inflammatory dendritic cells in atopic dermatitis are more heavily influenced by thymic stromal lymphopoietin, driving T cells toward the Th2 phenotype, Dr. Guttman-Yassky said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience member Dr. Jon M. Hanifin called the findings intriguing. He posed the question: What effect do the very high levels of IL-10 characteristically present in atopic dermatitis lesions have on the IL-23/Th17 axis? These elevated IL-10 levels constitute a key distinction between atopic dermatitis and psoriasis that has gone almost completely overlooked to date by researchers, said Dr. Hanifin, professor of dermatology at Oregon Health and Science University, Portland.

Dr. Guttman-Yassky replied that much work remains to be done in unravelling the immunologies of these two diseases, and conceded that she and her coworkers have not included measurement of IL-10.

'IL-17 is the master regulator of innate defense protein expression in keratinocytes.' DR. GUTTMAN-YASSKY

KYOTO, JAPAN — The predisposition to recurrent skin infections in atopic dermatitis might be explained by the recent discovery that interleukin-17 is relatively absent in lesional skin, said Dr. Emma Guttman-Yassky.

She and her coinvestigators demonstrated that interleukin-17 (IL-17) selectively induces epidermal keratinocytes to express innate defense proteins, including the antimicrobial peptides lipocalin 2, elafin, human beta-defensin-2, cathelicidin, and psoriasin.

When IL-17 is hypoexpressed in the skin barrier, as she and her colleagues have shown is the case in atopic dermatitis, it means having less of these antimicrobial peptides on-site—and that translates into diminished innate immune defense against microbial invasion, said Dr. Guttman-Yassky of Rockefeller University, New York, at an international investigative dermatology meeting.

"IL-17 is the master regulator of innate defense protein expression in keratinocytes," she said.

Dr. Guttman-Yassky reported on a study of biopsies obtained from lesional skin of 18 atopic dermatitis patients, both lesional and nonlesional skin of 15 psoriasis patients, and skin from 15 normal controls. Specimens were analyzed by gene microarray analysis, immunohistochemistry, and polymerase chain reaction.

According to Dr. Guttman-Yassky, the key findings included the following:

▸ Both IL-23 and the IL-23 receptor are highly activated in psoriatic lesions, compared with atopic dermatitis lesions, which in turn feature higher levels than in the nonlesional skin of psoriasis patients or normal skin of controls. IL-23 is known to activate IL-23 receptor-bearing Th17 T cells and induce them to produce IL-17 and IL-22.

▸ IL-17 is highly upregulated in psoriatic lesions, compared with atopic dermatitis lesions. This is probably in large part why psoriasis is not characterized by recurrent superinfections, she noted.

▸ Expression of lipocalin 2 and other antimicrobial peptides by epidermal keratinocytes is upregulated in psoriatic skin, compared with atopic dermatitis lesions or normal skin.

▸ Administration of IL-17 to keratinocytes in vitro results in strong upregulation of the innate defense peptides. Administration of interferon-gamma does not.

These observations led the investigators to several hypotheses regarding the nature of some of the key immunologic differences between atopic dermatitis and psoriasis, the two most common inflammatory skin diseases.

One hypothesis is that the IL-23/Th17 axis figures prominently in psoriasis but is largely absent in lesional skin of atopic dermatitis. This difference is due to major differences in the nature of the epidermal and dermal inflammatory dendritic cells involved in the two diseases, and the downstream cytokine environment these dendritic cells create.

The key dendritic cells in psoriasis upregulate tumor necrosis factor-α, IL-23, and IL-12, driving T cells toward the Th1 phenotype. In contrast, the inflammatory dendritic cells in atopic dermatitis are more heavily influenced by thymic stromal lymphopoietin, driving T cells toward the Th2 phenotype, Dr. Guttman-Yassky said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Audience member Dr. Jon M. Hanifin called the findings intriguing. He posed the question: What effect do the very high levels of IL-10 characteristically present in atopic dermatitis lesions have on the IL-23/Th17 axis? These elevated IL-10 levels constitute a key distinction between atopic dermatitis and psoriasis that has gone almost completely overlooked to date by researchers, said Dr. Hanifin, professor of dermatology at Oregon Health and Science University, Portland.

Dr. Guttman-Yassky replied that much work remains to be done in unravelling the immunologies of these two diseases, and conceded that she and her coworkers have not included measurement of IL-10.

'IL-17 is the master regulator of innate defense protein expression in keratinocytes.' DR. GUTTMAN-YASSKY

KYOTO, JAPAN — Fexofenadine is the sole truly nonsedating antihistamine—and the only one that does not cause objectively measurable cognitive and psychomotor impairment at doses that are commonly used in clinical practice, said Dr. Kazuhiko Yanai.

Fexofenadine (Allegra) is the only antihistamine that doesn't permeate the blood-brain barrier and therefore cannot bind to CNS histamine1 (H1) receptors, explained Dr. Yanai, professor of pharmacology at Tohoku University, Sendai (Japan), at an international investigative dermatology meeting.

He is credited as a pioneer in utilizing PET scanning to measure brain H1 occupancy by antihistamines and in demonstrating that this measurement correlates with the degree of cognitive and psychomotor impairment.

Dr. Yanai categorizes antihistamines into three classes: fexofenadine, which does not cross the blood-brain barrier even at supratherapeutic doses; the "less sedating" antihistamines, which occupy roughly 20% or less of available cortical H1 receptors and are associated with little cognitive impairment at their approved doses; and "more sedating" antihistamines, which bind to 50% or more of brain H1 receptors at recommended doses.

The first-generation antihistamines belong in the more sedating category. The prototype is ketotifen, which Dr. Yanai called "the most sedating antihistamine ever made." He has shown that a 1-mg oral dose of ketotifen results in a 72% brain H1 occupancy rate (Br. J. Clin. Pharmacol. 2006;61:16–26).

Second-generation antihistamines, with the exception of fexofenadine, fall into the less sedating category, he continued.

Another speaker at the Sanofi-Aventis-sponsored symposium, Dr. Ian Hindmarch, took a harder-line stance. He argued that from a safety standpoint there is no such thing as mild cognitive/psychomotor impairment.

The often-cited distinction between first- and second-generation antihistamines is mostly marketing hype. Antihistamines ought properly to be categorized as either not binding to brain H1 receptors—a category to date occupied solely by fexofenadine—and everything else, according to Dr. Hindmarch, professor emeritus of psychopharmacology at the University of Surrey (England).

"I like to make the analogy to pregnancy. Women are either pregnant or not pregnant. There is no such thing as being a little bit pregnant. Just the same, there's no such thing as being a little bit impaired. … Even a slight degree of impairment can cause an accident if the circumstances are present. All impairment is impairment, and it is only the circumstances—the child who runs into the street—that determine whether that impairment is going to damage you," he asserted.

It is well established that a person can experience quantifiable antihistamine-induced impairment of memory, attention, reaction time, decisiveness, and psychomotor coordination without feeling sleepy or drowsy, according to Dr. Hindmarch. And while such impairment may be less evident with many of the second-generation antihistamines when prescribed at the doses approved for seasonal allergic rhinitis, these agents are often used at far higher, even heroic, doses in treating a variety of pruritic dermatologic diseases.

For example, the standard dosing of cetirizine (Zyrtec) or loratidine (Claritin) for allergic rhinitis is 10 mg/day. But a dosage of 40–50 mg/day is often required to achieve clinical efficacy in patients with idiopathic urticaria or atopic dermatitis. And brain H1 receptor occupancy as well as impairment of superior cognitive functions are antihistamine dose dependent, Dr. Hindmarch stressed at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Yanai and Dr. Hindmarch are both on the speakers bureau for Sanofi-Aventis, the manufacturer of Allegra.

Fexofenadineis the only antihistamine that doesn't permeate the blood-brain barrier. DR. YANAI

KYOTO, JAPAN — Fexofenadine is the sole truly nonsedating antihistamine—and the only one that does not cause objectively measurable cognitive and psychomotor impairment at doses that are commonly used in clinical practice, said Dr. Kazuhiko Yanai.

Fexofenadine (Allegra) is the only antihistamine that doesn't permeate the blood-brain barrier and therefore cannot bind to CNS histamine1 (H1) receptors, explained Dr. Yanai, professor of pharmacology at Tohoku University, Sendai (Japan), at an international investigative dermatology meeting.

He is credited as a pioneer in utilizing PET scanning to measure brain H1 occupancy by antihistamines and in demonstrating that this measurement correlates with the degree of cognitive and psychomotor impairment.

Dr. Yanai categorizes antihistamines into three classes: fexofenadine, which does not cross the blood-brain barrier even at supratherapeutic doses; the "less sedating" antihistamines, which occupy roughly 20% or less of available cortical H1 receptors and are associated with little cognitive impairment at their approved doses; and "more sedating" antihistamines, which bind to 50% or more of brain H1 receptors at recommended doses.

The first-generation antihistamines belong in the more sedating category. The prototype is ketotifen, which Dr. Yanai called "the most sedating antihistamine ever made." He has shown that a 1-mg oral dose of ketotifen results in a 72% brain H1 occupancy rate (Br. J. Clin. Pharmacol. 2006;61:16–26).

Second-generation antihistamines, with the exception of fexofenadine, fall into the less sedating category, he continued.

Another speaker at the Sanofi-Aventis-sponsored symposium, Dr. Ian Hindmarch, took a harder-line stance. He argued that from a safety standpoint there is no such thing as mild cognitive/psychomotor impairment.

The often-cited distinction between first- and second-generation antihistamines is mostly marketing hype. Antihistamines ought properly to be categorized as either not binding to brain H1 receptors—a category to date occupied solely by fexofenadine—and everything else, according to Dr. Hindmarch, professor emeritus of psychopharmacology at the University of Surrey (England).

"I like to make the analogy to pregnancy. Women are either pregnant or not pregnant. There is no such thing as being a little bit pregnant. Just the same, there's no such thing as being a little bit impaired. … Even a slight degree of impairment can cause an accident if the circumstances are present. All impairment is impairment, and it is only the circumstances—the child who runs into the street—that determine whether that impairment is going to damage you," he asserted.

It is well established that a person can experience quantifiable antihistamine-induced impairment of memory, attention, reaction time, decisiveness, and psychomotor coordination without feeling sleepy or drowsy, according to Dr. Hindmarch. And while such impairment may be less evident with many of the second-generation antihistamines when prescribed at the doses approved for seasonal allergic rhinitis, these agents are often used at far higher, even heroic, doses in treating a variety of pruritic dermatologic diseases.

For example, the standard dosing of cetirizine (Zyrtec) or loratidine (Claritin) for allergic rhinitis is 10 mg/day. But a dosage of 40–50 mg/day is often required to achieve clinical efficacy in patients with idiopathic urticaria or atopic dermatitis. And brain H1 receptor occupancy as well as impairment of superior cognitive functions are antihistamine dose dependent, Dr. Hindmarch stressed at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Yanai and Dr. Hindmarch are both on the speakers bureau for Sanofi-Aventis, the manufacturer of Allegra.

Fexofenadineis the only antihistamine that doesn't permeate the blood-brain barrier. DR. YANAI

KYOTO, JAPAN — Fexofenadine is the sole truly nonsedating antihistamine—and the only one that does not cause objectively measurable cognitive and psychomotor impairment at doses that are commonly used in clinical practice, said Dr. Kazuhiko Yanai.

Fexofenadine (Allegra) is the only antihistamine that doesn't permeate the blood-brain barrier and therefore cannot bind to CNS histamine1 (H1) receptors, explained Dr. Yanai, professor of pharmacology at Tohoku University, Sendai (Japan), at an international investigative dermatology meeting.

He is credited as a pioneer in utilizing PET scanning to measure brain H1 occupancy by antihistamines and in demonstrating that this measurement correlates with the degree of cognitive and psychomotor impairment.

Dr. Yanai categorizes antihistamines into three classes: fexofenadine, which does not cross the blood-brain barrier even at supratherapeutic doses; the "less sedating" antihistamines, which occupy roughly 20% or less of available cortical H1 receptors and are associated with little cognitive impairment at their approved doses; and "more sedating" antihistamines, which bind to 50% or more of brain H1 receptors at recommended doses.

The first-generation antihistamines belong in the more sedating category. The prototype is ketotifen, which Dr. Yanai called "the most sedating antihistamine ever made." He has shown that a 1-mg oral dose of ketotifen results in a 72% brain H1 occupancy rate (Br. J. Clin. Pharmacol. 2006;61:16–26).

Second-generation antihistamines, with the exception of fexofenadine, fall into the less sedating category, he continued.

Another speaker at the Sanofi-Aventis-sponsored symposium, Dr. Ian Hindmarch, took a harder-line stance. He argued that from a safety standpoint there is no such thing as mild cognitive/psychomotor impairment.

The often-cited distinction between first- and second-generation antihistamines is mostly marketing hype. Antihistamines ought properly to be categorized as either not binding to brain H1 receptors—a category to date occupied solely by fexofenadine—and everything else, according to Dr. Hindmarch, professor emeritus of psychopharmacology at the University of Surrey (England).

"I like to make the analogy to pregnancy. Women are either pregnant or not pregnant. There is no such thing as being a little bit pregnant. Just the same, there's no such thing as being a little bit impaired. … Even a slight degree of impairment can cause an accident if the circumstances are present. All impairment is impairment, and it is only the circumstances—the child who runs into the street—that determine whether that impairment is going to damage you," he asserted.

It is well established that a person can experience quantifiable antihistamine-induced impairment of memory, attention, reaction time, decisiveness, and psychomotor coordination without feeling sleepy or drowsy, according to Dr. Hindmarch. And while such impairment may be less evident with many of the second-generation antihistamines when prescribed at the doses approved for seasonal allergic rhinitis, these agents are often used at far higher, even heroic, doses in treating a variety of pruritic dermatologic diseases.

For example, the standard dosing of cetirizine (Zyrtec) or loratidine (Claritin) for allergic rhinitis is 10 mg/day. But a dosage of 40–50 mg/day is often required to achieve clinical efficacy in patients with idiopathic urticaria or atopic dermatitis. And brain H1 receptor occupancy as well as impairment of superior cognitive functions are antihistamine dose dependent, Dr. Hindmarch stressed at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Dr. Yanai and Dr. Hindmarch are both on the speakers bureau for Sanofi-Aventis, the manufacturer of Allegra.

Fexofenadineis the only antihistamine that doesn't permeate the blood-brain barrier. DR. YANAI

SAN DIEGO — Patients with atopic dermatitis are highly colonized with Staphylococcus aureus but do not appear to be preferentially infected with community-acquired methicillin-resistant S. aureus.

Up to 79% of patients with atopic dermatitis have S. aureus in their anterior nares, 64%–75% have it on their normal skin, and more than 90% have it on their lesional skin.

In contrast, up to 30% of atopic-free adults have S. aureus in their nasal carriage and 10% have it on their skin, Dr. Sheila Fallon Friedlander said at a conference sponsored by Rady Children's Hospital, San Diego.

A reason why patients with atopic dermatitis may have trouble with S. aureus is that they appear to lack an adequate number of cathelicidins, said Dr. Friedlander, director of pediatric dermatology at the University of California, San Francisco.

"The end result clinically is that they don't have as much antimicrobial peptide helping to ward off infection. Atopics also have an impaired skin barrier, sometimes as a result of abnormal or decreased filaggrin. With increasing dryness and lack of appropriate adhesion, there is also increased skin surface area for the S. aureus to adhere to," she said.

In addition, she said S. aureus can elaborate superantigens, "which have the ability to stimulate the production of alternative glucocorticoid receptors. These receptors are more resistant to the effects of steroids. So often when S. aureus is present in the skin, there is elaboration of a receptor [that] makes it more difficult for the patient to respond to topical corticosteroid treatment."

A recent study estimated that 40%–66% of patients with atopic dermatitis develop S. aureus skin infections (Pediatr. Derm. 2000;17:111–4). Another concluded that the condition is a risk factor for invasive S. aureus infection in this patient population, including bacteremia, osteomyelitis, and endocarditis (Am. J. Med. 2005;118:1048–51).

However, Dr. Friedlander described the link between atopic dermatitis and invasive disease as "a controversial issue" with data that remain unclear.

"In some papers, it appears that there are lower levels of invasive disease in patients with atopic dermatitis," she said. "Invasive disease does occur, but atopics don't seem to be at higher risk for invasive disease. Further studies are required to clarify this issue."

The good news is that patients with atopic dermatitis do not seem to be preferentially affected with community-acquired methicillin-resistant S. aureus (CA-MRSA). An estimated 6%–19% of children with atopic dermatitis were found to have the condition (Arch. Dermatol. 2002;138:939–41).

Another group of researchers concluded that the "observed incidence of cutaneous CA-MRSA lesions in patients with atopic dermatitis or other non-intact skin barrier is less than reported in other at-risk groups" (J. Clin. Dermatol. 2007;8:259–70).

Dr. Friedlander explained that, compared with the hospital-acquired form of MRSA, the community-acquired form is clonal, has many drug options, and has a predilection for skin disease. "It preferentially infects the skin; skin and soft tissue infections are what we see," she said. "But you must remember that you can have invasive disease from this organism."

Clinically, CA-MRSA presents as furuncles or folliculitis 65%–95% of the time. "Parents will say, 'my child keeps getting a spider bite,'" Dr. Friedlander said. Most patients look well, but 40%–50% will have fever.

Most often, CA-MRSA organisms possess Panton-Valentine leukocidin, a virulence factor that is a bicomponent cytotoxin. This virulent toxin "destroys our leukocytes by punching holes in the membrane," she said. "This leads to capillary dilation and significant necrosis."

CA-MRSA also may possess an aberrant fibronectin-binding protein gene, which enables the S. aureus "to adhere better to our tissue and therefore enhances invasion."

Incision and drainage alone appears to suffice in CA-MRSA skin and soft tissue lesions smaller than 5 cm. "If a lesion is bigger than that, you need to be aggressive," she said. "Please culture these lesions. In the old days, people used to drain these and throw the exudate away. Do not throw it away because the antibiotic susceptibility patterns differ from the hospital-acquired form, and you may need this information to determine the best therapy for your patient."

Dr. Friedlander often starts patients on clindamycin. However, some organisms may be resistant, and therefore you need to check for inducible resistance in these patients. "Sometimes you need to use trimethoprim/sulfamethoxazole," she said.

"In older children, you can use minocycline or doxycycline, but remember, these drugs can damage the teeth of young children, and I will not use tetracyclines in children less than 8 years of age."

Attempts to eradicate MRSA with various combinations of antibiotics have had mixed results, but recent studies have found the use of bleach baths in combination with nasal mupirocin to be useful.

Dr. Friedlander recommends adding one-quarter of a cup of Clorox to a regular bath and repeating this treatment two times a week. In addition, some experts apply mupirocin ointment twice a day to the nares for 1 week each month.

"If you don't repeat the mupirocin treatment for a week each month, the patient appears more likely to colonize," she said. "There is no absolutely clear superior, evidence-based regimen, but studies are ongoing and we may have some more information in the future."

Control of atopic dermatitis "is the first goal in preventing infection," she pointed out. "If you control the itching and maintain the skin barrier, you are less likely to have the patient self-inoculate with staph or any other organism."

Dr. Friedlander disclosed that she has received grant and research support, honoraria, and/or consulting fees from Barrier Therapeutics Inc., Medicis Pharmaceutical Corp., Sanofi-Aventis, and Stiefel Laboratories Inc.

This patient's family mistook an MRSA infection for multiple spider bites. Courtesy Dr. Sheila Fallon Friedlander

SAN DIEGO — Patients with atopic dermatitis are highly colonized with Staphylococcus aureus but do not appear to be preferentially infected with community-acquired methicillin-resistant S. aureus.

Up to 79% of patients with atopic dermatitis have S. aureus in their anterior nares, 64%–75% have it on their normal skin, and more than 90% have it on their lesional skin.

In contrast, up to 30% of atopic-free adults have S. aureus in their nasal carriage and 10% have it on their skin, Dr. Sheila Fallon Friedlander said at a conference sponsored by Rady Children's Hospital, San Diego.

A reason why patients with atopic dermatitis may have trouble with S. aureus is that they appear to lack an adequate number of cathelicidins, said Dr. Friedlander, director of pediatric dermatology at the University of California, San Francisco.

"The end result clinically is that they don't have as much antimicrobial peptide helping to ward off infection. Atopics also have an impaired skin barrier, sometimes as a result of abnormal or decreased filaggrin. With increasing dryness and lack of appropriate adhesion, there is also increased skin surface area for the S. aureus to adhere to," she said.

In addition, she said S. aureus can elaborate superantigens, "which have the ability to stimulate the production of alternative glucocorticoid receptors. These receptors are more resistant to the effects of steroids. So often when S. aureus is present in the skin, there is elaboration of a receptor [that] makes it more difficult for the patient to respond to topical corticosteroid treatment."

A recent study estimated that 40%–66% of patients with atopic dermatitis develop S. aureus skin infections (Pediatr. Derm. 2000;17:111–4). Another concluded that the condition is a risk factor for invasive S. aureus infection in this patient population, including bacteremia, osteomyelitis, and endocarditis (Am. J. Med. 2005;118:1048–51).

However, Dr. Friedlander described the link between atopic dermatitis and invasive disease as "a controversial issue" with data that remain unclear.

"In some papers, it appears that there are lower levels of invasive disease in patients with atopic dermatitis," she said. "Invasive disease does occur, but atopics don't seem to be at higher risk for invasive disease. Further studies are required to clarify this issue."

The good news is that patients with atopic dermatitis do not seem to be preferentially affected with community-acquired methicillin-resistant S. aureus (CA-MRSA). An estimated 6%–19% of children with atopic dermatitis were found to have the condition (Arch. Dermatol. 2002;138:939–41).

Another group of researchers concluded that the "observed incidence of cutaneous CA-MRSA lesions in patients with atopic dermatitis or other non-intact skin barrier is less than reported in other at-risk groups" (J. Clin. Dermatol. 2007;8:259–70).

Dr. Friedlander explained that, compared with the hospital-acquired form of MRSA, the community-acquired form is clonal, has many drug options, and has a predilection for skin disease. "It preferentially infects the skin; skin and soft tissue infections are what we see," she said. "But you must remember that you can have invasive disease from this organism."

Clinically, CA-MRSA presents as furuncles or folliculitis 65%–95% of the time. "Parents will say, 'my child keeps getting a spider bite,'" Dr. Friedlander said. Most patients look well, but 40%–50% will have fever.

Most often, CA-MRSA organisms possess Panton-Valentine leukocidin, a virulence factor that is a bicomponent cytotoxin. This virulent toxin "destroys our leukocytes by punching holes in the membrane," she said. "This leads to capillary dilation and significant necrosis."

CA-MRSA also may possess an aberrant fibronectin-binding protein gene, which enables the S. aureus "to adhere better to our tissue and therefore enhances invasion."

Incision and drainage alone appears to suffice in CA-MRSA skin and soft tissue lesions smaller than 5 cm. "If a lesion is bigger than that, you need to be aggressive," she said. "Please culture these lesions. In the old days, people used to drain these and throw the exudate away. Do not throw it away because the antibiotic susceptibility patterns differ from the hospital-acquired form, and you may need this information to determine the best therapy for your patient."

Dr. Friedlander often starts patients on clindamycin. However, some organisms may be resistant, and therefore you need to check for inducible resistance in these patients. "Sometimes you need to use trimethoprim/sulfamethoxazole," she said.

"In older children, you can use minocycline or doxycycline, but remember, these drugs can damage the teeth of young children, and I will not use tetracyclines in children less than 8 years of age."

Attempts to eradicate MRSA with various combinations of antibiotics have had mixed results, but recent studies have found the use of bleach baths in combination with nasal mupirocin to be useful.

Dr. Friedlander recommends adding one-quarter of a cup of Clorox to a regular bath and repeating this treatment two times a week. In addition, some experts apply mupirocin ointment twice a day to the nares for 1 week each month.

"If you don't repeat the mupirocin treatment for a week each month, the patient appears more likely to colonize," she said. "There is no absolutely clear superior, evidence-based regimen, but studies are ongoing and we may have some more information in the future."

Control of atopic dermatitis "is the first goal in preventing infection," she pointed out. "If you control the itching and maintain the skin barrier, you are less likely to have the patient self-inoculate with staph or any other organism."

Dr. Friedlander disclosed that she has received grant and research support, honoraria, and/or consulting fees from Barrier Therapeutics Inc., Medicis Pharmaceutical Corp., Sanofi-Aventis, and Stiefel Laboratories Inc.

This patient's family mistook an MRSA infection for multiple spider bites. Courtesy Dr. Sheila Fallon Friedlander

SAN DIEGO — Patients with atopic dermatitis are highly colonized with Staphylococcus aureus but do not appear to be preferentially infected with community-acquired methicillin-resistant S. aureus.

Up to 79% of patients with atopic dermatitis have S. aureus in their anterior nares, 64%–75% have it on their normal skin, and more than 90% have it on their lesional skin.

In contrast, up to 30% of atopic-free adults have S. aureus in their nasal carriage and 10% have it on their skin, Dr. Sheila Fallon Friedlander said at a conference sponsored by Rady Children's Hospital, San Diego.

A reason why patients with atopic dermatitis may have trouble with S. aureus is that they appear to lack an adequate number of cathelicidins, said Dr. Friedlander, director of pediatric dermatology at the University of California, San Francisco.

"The end result clinically is that they don't have as much antimicrobial peptide helping to ward off infection. Atopics also have an impaired skin barrier, sometimes as a result of abnormal or decreased filaggrin. With increasing dryness and lack of appropriate adhesion, there is also increased skin surface area for the S. aureus to adhere to," she said.

In addition, she said S. aureus can elaborate superantigens, "which have the ability to stimulate the production of alternative glucocorticoid receptors. These receptors are more resistant to the effects of steroids. So often when S. aureus is present in the skin, there is elaboration of a receptor [that] makes it more difficult for the patient to respond to topical corticosteroid treatment."

A recent study estimated that 40%–66% of patients with atopic dermatitis develop S. aureus skin infections (Pediatr. Derm. 2000;17:111–4). Another concluded that the condition is a risk factor for invasive S. aureus infection in this patient population, including bacteremia, osteomyelitis, and endocarditis (Am. J. Med. 2005;118:1048–51).

However, Dr. Friedlander described the link between atopic dermatitis and invasive disease as "a controversial issue" with data that remain unclear.

"In some papers, it appears that there are lower levels of invasive disease in patients with atopic dermatitis," she said. "Invasive disease does occur, but atopics don't seem to be at higher risk for invasive disease. Further studies are required to clarify this issue."

The good news is that patients with atopic dermatitis do not seem to be preferentially affected with community-acquired methicillin-resistant S. aureus (CA-MRSA). An estimated 6%–19% of children with atopic dermatitis were found to have the condition (Arch. Dermatol. 2002;138:939–41).

Another group of researchers concluded that the "observed incidence of cutaneous CA-MRSA lesions in patients with atopic dermatitis or other non-intact skin barrier is less than reported in other at-risk groups" (J. Clin. Dermatol. 2007;8:259–70).

Dr. Friedlander explained that, compared with the hospital-acquired form of MRSA, the community-acquired form is clonal, has many drug options, and has a predilection for skin disease. "It preferentially infects the skin; skin and soft tissue infections are what we see," she said. "But you must remember that you can have invasive disease from this organism."

Clinically, CA-MRSA presents as furuncles or folliculitis 65%–95% of the time. "Parents will say, 'my child keeps getting a spider bite,'" Dr. Friedlander said. Most patients look well, but 40%–50% will have fever.

Most often, CA-MRSA organisms possess Panton-Valentine leukocidin, a virulence factor that is a bicomponent cytotoxin. This virulent toxin "destroys our leukocytes by punching holes in the membrane," she said. "This leads to capillary dilation and significant necrosis."

CA-MRSA also may possess an aberrant fibronectin-binding protein gene, which enables the S. aureus "to adhere better to our tissue and therefore enhances invasion."

Incision and drainage alone appears to suffice in CA-MRSA skin and soft tissue lesions smaller than 5 cm. "If a lesion is bigger than that, you need to be aggressive," she said. "Please culture these lesions. In the old days, people used to drain these and throw the exudate away. Do not throw it away because the antibiotic susceptibility patterns differ from the hospital-acquired form, and you may need this information to determine the best therapy for your patient."

Dr. Friedlander often starts patients on clindamycin. However, some organisms may be resistant, and therefore you need to check for inducible resistance in these patients. "Sometimes you need to use trimethoprim/sulfamethoxazole," she said.

"In older children, you can use minocycline or doxycycline, but remember, these drugs can damage the teeth of young children, and I will not use tetracyclines in children less than 8 years of age."

Attempts to eradicate MRSA with various combinations of antibiotics have had mixed results, but recent studies have found the use of bleach baths in combination with nasal mupirocin to be useful.

Dr. Friedlander recommends adding one-quarter of a cup of Clorox to a regular bath and repeating this treatment two times a week. In addition, some experts apply mupirocin ointment twice a day to the nares for 1 week each month.

"If you don't repeat the mupirocin treatment for a week each month, the patient appears more likely to colonize," she said. "There is no absolutely clear superior, evidence-based regimen, but studies are ongoing and we may have some more information in the future."

Control of atopic dermatitis "is the first goal in preventing infection," she pointed out. "If you control the itching and maintain the skin barrier, you are less likely to have the patient self-inoculate with staph or any other organism."

Dr. Friedlander disclosed that she has received grant and research support, honoraria, and/or consulting fees from Barrier Therapeutics Inc., Medicis Pharmaceutical Corp., Sanofi-Aventis, and Stiefel Laboratories Inc.

This patient's family mistook an MRSA infection for multiple spider bites. Courtesy Dr. Sheila Fallon Friedlander

KYOTO, JAPAN — Topical EpiCeram is an effective stand-alone therapy for moderate to severe pediatric atopic dermatitis, according to results of a clinical trial.

This physiologic skin barrier repair cream proved itself the equal of fluticasone proprionate cream (Cutivate) in a 113-patient multicenter randomized head-to-head comparison, Dr. Jeffrey L. Sugarman reported at an international investigative dermatology meeting.

The observed improvement with EpiCeram in clinical disease severity scores was not as fast as with the midstrength topical steroid. However, by the conclusion of the 4-week, investigator-blinded trial the two groups showed statistically and clinically similar gains in the Scoring Atopic Dermatitis (SCORAD) index, itching scores, and sleep habits, said Dr. Sugarman, a dermatologist in private practice in Santa Rosa, Calif., and at the University of California, San Francisco.

"I think EpiCeram is an important advance in the management of atopic dermatitis," he said in an interview at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

"It's a well thought-out barrier cream that utilizes our current understanding of the skin barrier in atopic dermatitis in its design and formulation," he added.

Indeed, EpiCeram is emblematic of a new paradigm in atopic dermatitis therapy that is based upon targeted, disease-specific lipid replacement, with a resultant marked reduction in the need for topical steroids or immunomodulators. The aim is to repair defective skin barrier function. This is in line with current thinking regarding the pathogenesis of atopic dermatitis, which holds that defective barrier function is the driver of disease activity rather than a consequence of an underlying immunologic defect, Dr. Sugarman continued.

The 113 participants in the clinical trial ranged in age from 6 months to 18 years. From a mean baseline SCORAD of 36, the EpiCeram-treated group showed a 47% improvement after 2 weeks and a 57% improvement after 4 weeks. The 4-week gain was statistically similar to the mean 69% improvement after 4 weeks of fluticasone, although the mean 61% improvement in SCORAD after 2 weeks of fluticasone was significantly better than with EpiCeram at that time point.

After 2 weeks of twice-daily therapy, only 4% of patients in the EpiCeram group showed a greater than 75% improvement in SCORAD scores, compared with 20% on fluticasone. By 4 weeks, 21% of EpiCeram-treated patients had exceeded this threshold, similar to the 26% rate in the fluticasone group.

Pruritis scores improved from a mean baseline of 6.1 on a 10-point scale to 3.5 with EpiCeram and 3.7 with fluticasone after 4 weeks. Sleep habits also improved significantly from a mean baseline of 3.5 on a 10-point scale to 2.6 with EpiCeram and 2.8 with fluticasone.

The study was sponsored by Ceregenix Corp., which has received Food and Drug Administration marketing approval for EpiCeram. Dr. Sugarman indicated he has no financial relationship with the company.

Ceregenix has granted exclusive EpiCeram distribution and marketing rights in the United States to Dr. Reddy's Laboratories Ltd., which plans to launch the prescription cream this fall.

KYOTO, JAPAN — Topical EpiCeram is an effective stand-alone therapy for moderate to severe pediatric atopic dermatitis, according to results of a clinical trial.

This physiologic skin barrier repair cream proved itself the equal of fluticasone proprionate cream (Cutivate) in a 113-patient multicenter randomized head-to-head comparison, Dr. Jeffrey L. Sugarman reported at an international investigative dermatology meeting.

The observed improvement with EpiCeram in clinical disease severity scores was not as fast as with the midstrength topical steroid. However, by the conclusion of the 4-week, investigator-blinded trial the two groups showed statistically and clinically similar gains in the Scoring Atopic Dermatitis (SCORAD) index, itching scores, and sleep habits, said Dr. Sugarman, a dermatologist in private practice in Santa Rosa, Calif., and at the University of California, San Francisco.

"I think EpiCeram is an important advance in the management of atopic dermatitis," he said in an interview at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

"It's a well thought-out barrier cream that utilizes our current understanding of the skin barrier in atopic dermatitis in its design and formulation," he added.

Indeed, EpiCeram is emblematic of a new paradigm in atopic dermatitis therapy that is based upon targeted, disease-specific lipid replacement, with a resultant marked reduction in the need for topical steroids or immunomodulators. The aim is to repair defective skin barrier function. This is in line with current thinking regarding the pathogenesis of atopic dermatitis, which holds that defective barrier function is the driver of disease activity rather than a consequence of an underlying immunologic defect, Dr. Sugarman continued.

The 113 participants in the clinical trial ranged in age from 6 months to 18 years. From a mean baseline SCORAD of 36, the EpiCeram-treated group showed a 47% improvement after 2 weeks and a 57% improvement after 4 weeks. The 4-week gain was statistically similar to the mean 69% improvement after 4 weeks of fluticasone, although the mean 61% improvement in SCORAD after 2 weeks of fluticasone was significantly better than with EpiCeram at that time point.

After 2 weeks of twice-daily therapy, only 4% of patients in the EpiCeram group showed a greater than 75% improvement in SCORAD scores, compared with 20% on fluticasone. By 4 weeks, 21% of EpiCeram-treated patients had exceeded this threshold, similar to the 26% rate in the fluticasone group.

Pruritis scores improved from a mean baseline of 6.1 on a 10-point scale to 3.5 with EpiCeram and 3.7 with fluticasone after 4 weeks. Sleep habits also improved significantly from a mean baseline of 3.5 on a 10-point scale to 2.6 with EpiCeram and 2.8 with fluticasone.

The study was sponsored by Ceregenix Corp., which has received Food and Drug Administration marketing approval for EpiCeram. Dr. Sugarman indicated he has no financial relationship with the company.

Ceregenix has granted exclusive EpiCeram distribution and marketing rights in the United States to Dr. Reddy's Laboratories Ltd., which plans to launch the prescription cream this fall.

KYOTO, JAPAN — Topical EpiCeram is an effective stand-alone therapy for moderate to severe pediatric atopic dermatitis, according to results of a clinical trial.

This physiologic skin barrier repair cream proved itself the equal of fluticasone proprionate cream (Cutivate) in a 113-patient multicenter randomized head-to-head comparison, Dr. Jeffrey L. Sugarman reported at an international investigative dermatology meeting.

The observed improvement with EpiCeram in clinical disease severity scores was not as fast as with the midstrength topical steroid. However, by the conclusion of the 4-week, investigator-blinded trial the two groups showed statistically and clinically similar gains in the Scoring Atopic Dermatitis (SCORAD) index, itching scores, and sleep habits, said Dr. Sugarman, a dermatologist in private practice in Santa Rosa, Calif., and at the University of California, San Francisco.

"I think EpiCeram is an important advance in the management of atopic dermatitis," he said in an interview at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

"It's a well thought-out barrier cream that utilizes our current understanding of the skin barrier in atopic dermatitis in its design and formulation," he added.

Indeed, EpiCeram is emblematic of a new paradigm in atopic dermatitis therapy that is based upon targeted, disease-specific lipid replacement, with a resultant marked reduction in the need for topical steroids or immunomodulators. The aim is to repair defective skin barrier function. This is in line with current thinking regarding the pathogenesis of atopic dermatitis, which holds that defective barrier function is the driver of disease activity rather than a consequence of an underlying immunologic defect, Dr. Sugarman continued.

The 113 participants in the clinical trial ranged in age from 6 months to 18 years. From a mean baseline SCORAD of 36, the EpiCeram-treated group showed a 47% improvement after 2 weeks and a 57% improvement after 4 weeks. The 4-week gain was statistically similar to the mean 69% improvement after 4 weeks of fluticasone, although the mean 61% improvement in SCORAD after 2 weeks of fluticasone was significantly better than with EpiCeram at that time point.

After 2 weeks of twice-daily therapy, only 4% of patients in the EpiCeram group showed a greater than 75% improvement in SCORAD scores, compared with 20% on fluticasone. By 4 weeks, 21% of EpiCeram-treated patients had exceeded this threshold, similar to the 26% rate in the fluticasone group.

Pruritis scores improved from a mean baseline of 6.1 on a 10-point scale to 3.5 with EpiCeram and 3.7 with fluticasone after 4 weeks. Sleep habits also improved significantly from a mean baseline of 3.5 on a 10-point scale to 2.6 with EpiCeram and 2.8 with fluticasone.

The study was sponsored by Ceregenix Corp., which has received Food and Drug Administration marketing approval for EpiCeram. Dr. Sugarman indicated he has no financial relationship with the company.

Ceregenix has granted exclusive EpiCeram distribution and marketing rights in the United States to Dr. Reddy's Laboratories Ltd., which plans to launch the prescription cream this fall.

SAN DIEGO — Barrier products may play a role as adjuvant therapy for patients with atopic dermatitis, but better studies are needed to demonstrate their efficacy.

That's the conclusion Dr. Andrew C. Krakowski made about three barrier products he discussed at a meeting on skin disorders sponsored by Rady Children's Hospital: palmitamide monoethanolamine (PEA) nonsteroidal cream (MimyX), hydrolipidic cream MAS063DP (Atopiclair), and ceramide-based emulsion (EpiCeram).

These products are 510(k) medical devices that have been cleared for marketing by the Food and Drug Administration. The manufacturers claim that they contain ingredients that might help to replace normal epidermal lipids, improve skin hydration, decrease skin barrier dysfunction, and relieve the atopic dermatitis symptoms of stinging, burning, and pruritus.

Such features are important, Dr. Krakowski said, because "we know that barrier dysfunction correlates with atopic dermatitis severity and we think there is a possible increased allergy absorption that happens through the skin of our atopic dermatitis patients. We also know that atopic dermatitis skin is a great setup for microbial colonization, and that puts you at increased risk of secondary infection. We also have good data that a disrepaired skin barrier leads to increased transepidermal water loss."

There are several barrier products currently on the market, but he limited his discussion to the three that have been studied recently:

▸ EpiCeram. Licensed by the University of California and manufactured by Ceragenix Pharmaceuticals Inc., EpiCeram is a combination of ceramides, cholesterols, and fatty acids that is expected to hit the U.S. market this fall, said Dr. Krakowski. The current cost is not known.

In a multicenter, randomized study sponsored by Ceragenix and presented as a poster at the 2008 annual meeting of the Society of Pediatric Dermatology, investigators compared 4 weeks of twice-daily ceramide-based emulsion to fluticasone propionate in children with moderate to severe atopic dermatitis. (See related story below.)

On day 14, subjects in the fluticasone group had significantly better Scoring Atopic Dermatitis (SCORAD) scores, compared with those in the ceramide-based emulsion group. By day 28, there were no significant differences in SCORAD scores between the two groups.

In a second multicenter, randomized study that included patients from Rady Children's Hospital, investigators compared 4 weeks of twice-daily ceramide-based emulsion to pimecrolimus in 38 pediatric subjects with mild to moderate atopic dermatitis. No intention-to-treat analysis was performed.

Subjects in both groups demonstrated significant improvement in Investigator Global Assessment (IGA) scores at days 14 and 28. "There was also no significant difference in pruritus between the two groups, but it wasn't clear if there was any improvement," said Dr. Krakowski, a first-year dermatology resident at the University of California, San Diego.

Subjects in the ceramide-based emulsion group had no significant improvement from baseline in Eczema Area and Severity Index (EASI) scores. By day 14, subjects in the pimecrolimus group had significantly better EASI scores, compared with their counterparts in the ceramide emulsion group. By day 28, there were no differences in median score reductions between the groups.

▸ MimyX. Manufactured by Stiefel Laboratories Inc., this water-based product is described as a fragrance-, dye-, and preservative-free emulsion to be used three times a day or as needed. According to the manufacturer's Web site, it comes as a 140-g tube, with a cost of $101, or about $22 per ounce.

The main ingredient is PEA, which is found naturally in the stratum granulosum and is thought to downregulate inflammatory response. "It's a cannabinoid agonist that is believed to modulate mast cells and immune cells, theoretically reducing histamines, cytokines, and IL-4, −6, and −8," Dr. Krakowski added. "It's also thought to bind CB2 receptors on cutaneous nerves and decrease the transmission of pruritus."

In an international open-label study, investigators assessed the effects of the PEA nonsteroidal cream applied at least twice daily for 38 days in 2,456 patients with mild to moderate atopic dermatitis (J. Eur. Acad. Dermatol. Venereol. 2008;22:73–82). Of the 2,456 patients, 923 were 12 years of age or younger.

By the end of the study, physician assessment scores demonstrated that pruritus improved by 56%, erythema by 54%, dryness by 57%, lichenification by 55%, and excoriations by 63%.

The investigators also found that by the end of the treatment period, 63% of children reduced their use of topical corticosteroids, compared with 53% of adults. In addition, 34% of subjects were able to stop using their topical corticosteroid altogether and 12% were able to switch to a lower-potency steroid.

▸ Atopiclair. Manufactured by Graceway Pharmaceuticals LLC, this product contains hyaluronic acid, Vitis vinifera (grape leaf extract), telmesteine, glycyrrhetinic acid (licorice extract), and shea butter, a derivative of shea nut oil. The product is described as dye- and fragrance-free and is used 2–3 times per day or as needed. It comes in a 100-g tube and costs about $34 per ounce.

In a multicenter, randomized, double-blind, vehicle-controlled trial, 106 infants and children with mild to moderate atopic dermatitis applied hydrolipidic cream MAS063DP or vehicle three times a day to past, current, or "reasonable future" sites as monotherapy for 43 days (J. Pediatr. 2008;152:854–9). The mean age of subjects was 5 years.

One target lesion was chosen by investigators for evaluation and photography (mostly identified on extremities). Success was defined as reaching an IGA score of 0 (clear) or 1 (almost clear).

In an intention-to-treat analysis, 53 of 69 subjects (77%) in the hydrolipidic cream group achieved a score of 0 or 1 at day 22, compared with none in the vehicle group. "The vehicle used in the study wasn't your normal petrolatum vehicle," Dr. Krakowski noted. "It was the vehicle the hydrolipidic cream came in."

Pruritus, EASI scores, subject and caregiver assessment of global response, onset and duration of itch relief, and need for rescue medication were all significantly improved in the treatment group, compared with the vehicle group.

"I think barrier products could be helpful as adjuvant treatment for atopic dermatitis," he commented. "I think the cost of these products needs to be reconciled with their cost-effectiveness; most of these products may not be covered by insurance. We also need better head-to-head, long-term, pediatric-specific trials to demonstrate efficacy of these products for treating flares directly and for maintenance therapy over the long term."

Dr. Krakowski disclosed having had no relevant conflicts of interest.

SAN DIEGO — Barrier products may play a role as adjuvant therapy for patients with atopic dermatitis, but better studies are needed to demonstrate their efficacy.

That's the conclusion Dr. Andrew C. Krakowski made about three barrier products he discussed at a meeting on skin disorders sponsored by Rady Children's Hospital: palmitamide monoethanolamine (PEA) nonsteroidal cream (MimyX), hydrolipidic cream MAS063DP (Atopiclair), and ceramide-based emulsion (EpiCeram).

These products are 510(k) medical devices that have been cleared for marketing by the Food and Drug Administration. The manufacturers claim that they contain ingredients that might help to replace normal epidermal lipids, improve skin hydration, decrease skin barrier dysfunction, and relieve the atopic dermatitis symptoms of stinging, burning, and pruritus.

Such features are important, Dr. Krakowski said, because "we know that barrier dysfunction correlates with atopic dermatitis severity and we think there is a possible increased allergy absorption that happens through the skin of our atopic dermatitis patients. We also know that atopic dermatitis skin is a great setup for microbial colonization, and that puts you at increased risk of secondary infection. We also have good data that a disrepaired skin barrier leads to increased transepidermal water loss."

There are several barrier products currently on the market, but he limited his discussion to the three that have been studied recently:

▸ EpiCeram. Licensed by the University of California and manufactured by Ceragenix Pharmaceuticals Inc., EpiCeram is a combination of ceramides, cholesterols, and fatty acids that is expected to hit the U.S. market this fall, said Dr. Krakowski. The current cost is not known.

In a multicenter, randomized study sponsored by Ceragenix and presented as a poster at the 2008 annual meeting of the Society of Pediatric Dermatology, investigators compared 4 weeks of twice-daily ceramide-based emulsion to fluticasone propionate in children with moderate to severe atopic dermatitis. (See related story below.)

On day 14, subjects in the fluticasone group had significantly better Scoring Atopic Dermatitis (SCORAD) scores, compared with those in the ceramide-based emulsion group. By day 28, there were no significant differences in SCORAD scores between the two groups.

In a second multicenter, randomized study that included patients from Rady Children's Hospital, investigators compared 4 weeks of twice-daily ceramide-based emulsion to pimecrolimus in 38 pediatric subjects with mild to moderate atopic dermatitis. No intention-to-treat analysis was performed.

Subjects in both groups demonstrated significant improvement in Investigator Global Assessment (IGA) scores at days 14 and 28. "There was also no significant difference in pruritus between the two groups, but it wasn't clear if there was any improvement," said Dr. Krakowski, a first-year dermatology resident at the University of California, San Diego.

Subjects in the ceramide-based emulsion group had no significant improvement from baseline in Eczema Area and Severity Index (EASI) scores. By day 14, subjects in the pimecrolimus group had significantly better EASI scores, compared with their counterparts in the ceramide emulsion group. By day 28, there were no differences in median score reductions between the groups.

▸ MimyX. Manufactured by Stiefel Laboratories Inc., this water-based product is described as a fragrance-, dye-, and preservative-free emulsion to be used three times a day or as needed. According to the manufacturer's Web site, it comes as a 140-g tube, with a cost of $101, or about $22 per ounce.

The main ingredient is PEA, which is found naturally in the stratum granulosum and is thought to downregulate inflammatory response. "It's a cannabinoid agonist that is believed to modulate mast cells and immune cells, theoretically reducing histamines, cytokines, and IL-4, −6, and −8," Dr. Krakowski added. "It's also thought to bind CB2 receptors on cutaneous nerves and decrease the transmission of pruritus."

In an international open-label study, investigators assessed the effects of the PEA nonsteroidal cream applied at least twice daily for 38 days in 2,456 patients with mild to moderate atopic dermatitis (J. Eur. Acad. Dermatol. Venereol. 2008;22:73–82). Of the 2,456 patients, 923 were 12 years of age or younger.

By the end of the study, physician assessment scores demonstrated that pruritus improved by 56%, erythema by 54%, dryness by 57%, lichenification by 55%, and excoriations by 63%.

The investigators also found that by the end of the treatment period, 63% of children reduced their use of topical corticosteroids, compared with 53% of adults. In addition, 34% of subjects were able to stop using their topical corticosteroid altogether and 12% were able to switch to a lower-potency steroid.

▸ Atopiclair. Manufactured by Graceway Pharmaceuticals LLC, this product contains hyaluronic acid, Vitis vinifera (grape leaf extract), telmesteine, glycyrrhetinic acid (licorice extract), and shea butter, a derivative of shea nut oil. The product is described as dye- and fragrance-free and is used 2–3 times per day or as needed. It comes in a 100-g tube and costs about $34 per ounce.

In a multicenter, randomized, double-blind, vehicle-controlled trial, 106 infants and children with mild to moderate atopic dermatitis applied hydrolipidic cream MAS063DP or vehicle three times a day to past, current, or "reasonable future" sites as monotherapy for 43 days (J. Pediatr. 2008;152:854–9). The mean age of subjects was 5 years.

One target lesion was chosen by investigators for evaluation and photography (mostly identified on extremities). Success was defined as reaching an IGA score of 0 (clear) or 1 (almost clear).

In an intention-to-treat analysis, 53 of 69 subjects (77%) in the hydrolipidic cream group achieved a score of 0 or 1 at day 22, compared with none in the vehicle group. "The vehicle used in the study wasn't your normal petrolatum vehicle," Dr. Krakowski noted. "It was the vehicle the hydrolipidic cream came in."

Pruritus, EASI scores, subject and caregiver assessment of global response, onset and duration of itch relief, and need for rescue medication were all significantly improved in the treatment group, compared with the vehicle group.

"I think barrier products could be helpful as adjuvant treatment for atopic dermatitis," he commented. "I think the cost of these products needs to be reconciled with their cost-effectiveness; most of these products may not be covered by insurance. We also need better head-to-head, long-term, pediatric-specific trials to demonstrate efficacy of these products for treating flares directly and for maintenance therapy over the long term."

Dr. Krakowski disclosed having had no relevant conflicts of interest.

SAN DIEGO — Barrier products may play a role as adjuvant therapy for patients with atopic dermatitis, but better studies are needed to demonstrate their efficacy.

That's the conclusion Dr. Andrew C. Krakowski made about three barrier products he discussed at a meeting on skin disorders sponsored by Rady Children's Hospital: palmitamide monoethanolamine (PEA) nonsteroidal cream (MimyX), hydrolipidic cream MAS063DP (Atopiclair), and ceramide-based emulsion (EpiCeram).

These products are 510(k) medical devices that have been cleared for marketing by the Food and Drug Administration. The manufacturers claim that they contain ingredients that might help to replace normal epidermal lipids, improve skin hydration, decrease skin barrier dysfunction, and relieve the atopic dermatitis symptoms of stinging, burning, and pruritus.

Such features are important, Dr. Krakowski said, because "we know that barrier dysfunction correlates with atopic dermatitis severity and we think there is a possible increased allergy absorption that happens through the skin of our atopic dermatitis patients. We also know that atopic dermatitis skin is a great setup for microbial colonization, and that puts you at increased risk of secondary infection. We also have good data that a disrepaired skin barrier leads to increased transepidermal water loss."

There are several barrier products currently on the market, but he limited his discussion to the three that have been studied recently:

▸ EpiCeram. Licensed by the University of California and manufactured by Ceragenix Pharmaceuticals Inc., EpiCeram is a combination of ceramides, cholesterols, and fatty acids that is expected to hit the U.S. market this fall, said Dr. Krakowski. The current cost is not known.

In a multicenter, randomized study sponsored by Ceragenix and presented as a poster at the 2008 annual meeting of the Society of Pediatric Dermatology, investigators compared 4 weeks of twice-daily ceramide-based emulsion to fluticasone propionate in children with moderate to severe atopic dermatitis. (See related story below.)

On day 14, subjects in the fluticasone group had significantly better Scoring Atopic Dermatitis (SCORAD) scores, compared with those in the ceramide-based emulsion group. By day 28, there were no significant differences in SCORAD scores between the two groups.

In a second multicenter, randomized study that included patients from Rady Children's Hospital, investigators compared 4 weeks of twice-daily ceramide-based emulsion to pimecrolimus in 38 pediatric subjects with mild to moderate atopic dermatitis. No intention-to-treat analysis was performed.

Subjects in both groups demonstrated significant improvement in Investigator Global Assessment (IGA) scores at days 14 and 28. "There was also no significant difference in pruritus between the two groups, but it wasn't clear if there was any improvement," said Dr. Krakowski, a first-year dermatology resident at the University of California, San Diego.

Subjects in the ceramide-based emulsion group had no significant improvement from baseline in Eczema Area and Severity Index (EASI) scores. By day 14, subjects in the pimecrolimus group had significantly better EASI scores, compared with their counterparts in the ceramide emulsion group. By day 28, there were no differences in median score reductions between the groups.

▸ MimyX. Manufactured by Stiefel Laboratories Inc., this water-based product is described as a fragrance-, dye-, and preservative-free emulsion to be used three times a day or as needed. According to the manufacturer's Web site, it comes as a 140-g tube, with a cost of $101, or about $22 per ounce.

The main ingredient is PEA, which is found naturally in the stratum granulosum and is thought to downregulate inflammatory response. "It's a cannabinoid agonist that is believed to modulate mast cells and immune cells, theoretically reducing histamines, cytokines, and IL-4, −6, and −8," Dr. Krakowski added. "It's also thought to bind CB2 receptors on cutaneous nerves and decrease the transmission of pruritus."

In an international open-label study, investigators assessed the effects of the PEA nonsteroidal cream applied at least twice daily for 38 days in 2,456 patients with mild to moderate atopic dermatitis (J. Eur. Acad. Dermatol. Venereol. 2008;22:73–82). Of the 2,456 patients, 923 were 12 years of age or younger.

By the end of the study, physician assessment scores demonstrated that pruritus improved by 56%, erythema by 54%, dryness by 57%, lichenification by 55%, and excoriations by 63%.

The investigators also found that by the end of the treatment period, 63% of children reduced their use of topical corticosteroids, compared with 53% of adults. In addition, 34% of subjects were able to stop using their topical corticosteroid altogether and 12% were able to switch to a lower-potency steroid.

▸ Atopiclair. Manufactured by Graceway Pharmaceuticals LLC, this product contains hyaluronic acid, Vitis vinifera (grape leaf extract), telmesteine, glycyrrhetinic acid (licorice extract), and shea butter, a derivative of shea nut oil. The product is described as dye- and fragrance-free and is used 2–3 times per day or as needed. It comes in a 100-g tube and costs about $34 per ounce.

In a multicenter, randomized, double-blind, vehicle-controlled trial, 106 infants and children with mild to moderate atopic dermatitis applied hydrolipidic cream MAS063DP or vehicle three times a day to past, current, or "reasonable future" sites as monotherapy for 43 days (J. Pediatr. 2008;152:854–9). The mean age of subjects was 5 years.

One target lesion was chosen by investigators for evaluation and photography (mostly identified on extremities). Success was defined as reaching an IGA score of 0 (clear) or 1 (almost clear).

In an intention-to-treat analysis, 53 of 69 subjects (77%) in the hydrolipidic cream group achieved a score of 0 or 1 at day 22, compared with none in the vehicle group. "The vehicle used in the study wasn't your normal petrolatum vehicle," Dr. Krakowski noted. "It was the vehicle the hydrolipidic cream came in."

Pruritus, EASI scores, subject and caregiver assessment of global response, onset and duration of itch relief, and need for rescue medication were all significantly improved in the treatment group, compared with the vehicle group.

"I think barrier products could be helpful as adjuvant treatment for atopic dermatitis," he commented. "I think the cost of these products needs to be reconciled with their cost-effectiveness; most of these products may not be covered by insurance. We also need better head-to-head, long-term, pediatric-specific trials to demonstrate efficacy of these products for treating flares directly and for maintenance therapy over the long term."

Dr. Krakowski disclosed having had no relevant conflicts of interest.

Jeffrey L. Sugarman, MD, PhD

Epidermal barrier function is abnormal in individuals with atopic dermatitis (AD). It is controversial whether primary epidermal barrier abnormalities alone account for the physiological and clinical abnormalities found in those persons with AD or whether the observed barrier dysfunction is a consequence of primary immunologic abnormalities. Recent evidence is strengthening the argument for the former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has long been an important part of the therapy of AD. Advances in our understanding of the biology of the epidermal barrier and how this relates to the clinical manifestations of this disease has important consequences for new therapeutic approaches in the management of AD.

 *For a PDF of the full article, click on the link to the left of this introduction.

Jeffrey L. Sugarman, MD, PhD

Epidermal barrier function is abnormal in individuals with atopic dermatitis (AD). It is controversial whether primary epidermal barrier abnormalities alone account for the physiological and clinical abnormalities found in those persons with AD or whether the observed barrier dysfunction is a consequence of primary immunologic abnormalities. Recent evidence is strengthening the argument for the former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has long been an important part of the therapy of AD. Advances in our understanding of the biology of the epidermal barrier and how this relates to the clinical manifestations of this disease has important consequences for new therapeutic approaches in the management of AD.

 *For a PDF of the full article, click on the link to the left of this introduction.

Jeffrey L. Sugarman, MD, PhD

Epidermal barrier function is abnormal in individuals with atopic dermatitis (AD). It is controversial whether primary epidermal barrier abnormalities alone account for the physiological and clinical abnormalities found in those persons with AD or whether the observed barrier dysfunction is a consequence of primary immunologic abnormalities. Recent evidence is strengthening the argument for the former hypothesis. Attention to epidermal barrier care (ie, gentle skin care) has long been an important part of the therapy of AD. Advances in our understanding of the biology of the epidermal barrier and how this relates to the clinical manifestations of this disease has important consequences for new therapeutic approaches in the management of AD.

 *For a PDF of the full article, click on the link to the left of this introduction.

Mark Boguniewicz, MD, Noreen Nicol, MS, RN, FNP, Kim Kelsay, MD, and Donald YM Leung, MD, PhD

Atopic dermatitis is a common, complex disease that frequently follows a chronic, relapsing course. The disease can impact the quality of life (QOL) of patients and families to a significant degree. Patients and caregivers may focus on unproven triggers at the expense of proper skin care. A multidisciplinary approach is needed to comprehensively evaluate triggers and response to treatment, address confounding factors including sleep disruption, and educate patients and caregivers.

*For a PDF of the full article, click on the link to the left of this introduction.

Mark Boguniewicz, MD, Noreen Nicol, MS, RN, FNP, Kim Kelsay, MD, and Donald YM Leung, MD, PhD

Atopic dermatitis is a common, complex disease that frequently follows a chronic, relapsing course. The disease can impact the quality of life (QOL) of patients and families to a significant degree. Patients and caregivers may focus on unproven triggers at the expense of proper skin care. A multidisciplinary approach is needed to comprehensively evaluate triggers and response to treatment, address confounding factors including sleep disruption, and educate patients and caregivers.

*For a PDF of the full article, click on the link to the left of this introduction.

Mark Boguniewicz, MD, Noreen Nicol, MS, RN, FNP, Kim Kelsay, MD, and Donald YM Leung, MD, PhD

Atopic dermatitis is a common, complex disease that frequently follows a chronic, relapsing course. The disease can impact the quality of life (QOL) of patients and families to a significant degree. Patients and caregivers may focus on unproven triggers at the expense of proper skin care. A multidisciplinary approach is needed to comprehensively evaluate triggers and response to treatment, address confounding factors including sleep disruption, and educate patients and caregivers.

*For a PDF of the full article, click on the link to the left of this introduction.

Sara J. Brown, MBChB, BSc, MRCP, and Alan D. Irvine, MD, FRCPI

The discovery that null mutations in the filaggrin gene (FLG) are associated with atopic eczema represents the single most significant breakthrough in understanding the genetic basis of this complex disorder. The association has been replicated in multiple independent studies during the past 2 years with the use of various methodologies, from populations in Europe, the United States, and Japan. Filaggrin plays a key role in epidermal barrier function, and its association with atopic eczema emphasizes the importance of barrier dysfunction in eczema pathogenesis. This review aims to summarize the current state of knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic eczema, and other skin disorders, with an emphasis on potential clinical applications. Further research is needed to clarify the precise role of filaggrin in skin and systemic atopic disease, to pave the way for novel therapeutic interventions.

*For a PDF of the full article, click on the link to the left of this introduction.

Sara J. Brown, MBChB, BSc, MRCP, and Alan D. Irvine, MD, FRCPI

The discovery that null mutations in the filaggrin gene (FLG) are associated with atopic eczema represents the single most significant breakthrough in understanding the genetic basis of this complex disorder. The association has been replicated in multiple independent studies during the past 2 years with the use of various methodologies, from populations in Europe, the United States, and Japan. Filaggrin plays a key role in epidermal barrier function, and its association with atopic eczema emphasizes the importance of barrier dysfunction in eczema pathogenesis. This review aims to summarize the current state of knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic eczema, and other skin disorders, with an emphasis on potential clinical applications. Further research is needed to clarify the precise role of filaggrin in skin and systemic atopic disease, to pave the way for novel therapeutic interventions.

*For a PDF of the full article, click on the link to the left of this introduction.

Sara J. Brown, MBChB, BSc, MRCP, and Alan D. Irvine, MD, FRCPI

The discovery that null mutations in the filaggrin gene (FLG) are associated with atopic eczema represents the single most significant breakthrough in understanding the genetic basis of this complex disorder. The association has been replicated in multiple independent studies during the past 2 years with the use of various methodologies, from populations in Europe, the United States, and Japan. Filaggrin plays a key role in epidermal barrier function, and its association with atopic eczema emphasizes the importance of barrier dysfunction in eczema pathogenesis. This review aims to summarize the current state of knowledge regarding the role of FLG mutations in ichthyosis vulgaris, atopic eczema, and other skin disorders, with an emphasis on potential clinical applications. Further research is needed to clarify the precise role of filaggrin in skin and systemic atopic disease, to pave the way for novel therapeutic interventions.

*For a PDF of the full article, click on the link to the left of this introduction.