New Insights Into Atopic Dermatitis
Recent insights into the pathogenesis of atopic dermatitis (AD) and its role as a possible precursor to food and other allergies are driving treatments that seek to restore the skin's barrier function, experts say.
"The prevalence of AD is increasing, and it affects between 10 percent and 17 percent of the total United States population," with 80 percent to 90 percent of patients being diagnosed before age five and about half of them eventually outgrowing it (Ann Allergy Asthma Immunol. 1997 Sep;79(3):197-211), says Leon Kircik, M.D., clinical associate professor of dermatology at Indiana University, Indianapolis.
One in five affected
"More than 15 million patients have symptoms of AD," including 20 percent of American children and infants, he adds.
"And 60 percent of affected infants continue to have symptoms in adulthood (Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93)," Dr. Kircik says.
"Most of the time, patients with AD also suffer from secondary infections," including those caused by community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), Dr. Kircik notes.
Therefore, he says, "I suggest culturing every secondary infection" occurring with AD.
AD also can be a marker for other atopic diseases such as asthma, food allergies, hay fever, allergies and rhinitis, Dr. Kircik asserts.
There's also a theory that if one prevents AD from developing or from becoming severe, one will be able to prevent asthma developing later in life. The concept is called the atopic march (BMJ. 2002 Jun 8;324(7350): 1376-1379), Dr. Kircik explains.
Research inroads
Over the past several years, research into the pathogenesis of AD also has focused on the possibility that patients with this disease have a functional problem with their skin barrier, says Amy E. Gilliam, M.D., assistant clinical professor of pediatrics and dermatology at the University of California, San Francisco.
In particular, she says researchers have shown that this barrier dysfunction in patients with AD correlates with a reduction in ceramides, one of the three key stratum corneum lipids.
"Ceramides may also influence inflammatory responses, in addition to their contribution to effective barrier function," Dr. Gilliam says.
"Another recent development in the understanding of the pathogenesis of AD involves a study showing that there may be a genetic predisposition for AD," she says.
In particular, researchers have shown that an inherited reduction in the expression of filaggrin, a key protein involved in the formation of the skin barrier, is a major predisposing factor in AD (Nat Genet. 2006 Apr;38[4]:441-446. Epub 2006 Mar 19).
"This genetic mutation in filaggrin in affected families further supports the hypothesis that an impaired skin barrier plays a key role in the pathogenesis of AD," Dr. Gilliam says.
Similarly, Dr. Gilliam notes other studies have shown that the skin of patients with AD is deficient in certain antimicrobial peptides, specifically beta defensins and cathelicidins, which contribute to the skin's barrier against infection (J Invest Dermatol. 2005 Jul;125[1]:9-13).
Pharmaceutical armamentarium
In keeping with the foregoing developments, manufacturers have begun offering ceramide-based moisturizing creams and other barrier repair formulations, sources say.
Ceramide-based creams include TriCeram (Osmotics), EpiCeram (Ceragenix) and TriXera (Eau Thermale Avene), while products that have earned Food and Drug Administration (FDA) approval include Atopiclair (Sinclair Pharmaceuticals Ltd./Chester Valley) and Mimyx (PEA, Steifel), Dr. Gilliam says.
"Atopiclair and Mimyx do not contain ceramides, but multiple other agents that have anti-inflammatory and anti-pruritic properties," she tells Dermatology Times.
Both are indicated for the management and relief of itching, burning and pain associated with a variety of inflammatory and allergic dermatoses including atopic and contact dermatitis, Dr. Gilliam explains.
However, she says, "One of the caveats one should consider is that Atopiclair contains shea butter, which is a derivative of shea nut oil," to which patients may be allergic.
Moreover, Dr. Kircik says that in a study that compared Mimyx, Atopiclair and Eucerin (10 percent urea cream, Beiersdorf), "Mimyx decreased transepidermal water loss twice as well as Atopiclair and three times as well as petrolatum."
Overall, Dr. Kircik says, "The treatment of AD is changing."
Originally, he says physicians relied heavily on topical steroids, which are still used, but less frequently due to concerns for side effects such as systemic absorption, HPA suppression, atrophy, telangiectasia formation and tachyphylaxis.
Next, he says, "Everybody jumped on the steroid-sparing agents, namely the topical calcineurin inhibitors Elidel (pimecrolimus, Novartis) and Protopic (tacrolimus, Astellas)."
However, Dr. Kircik says that although dermatologists disagree with the FDA's decision to add black box warnings to these products' labels, "It has affected our prescribing patterns because everybody's afraid medically and legally to use those products on children less than two years old."
On a positive note, he says that the approval of Mimyx, Atopiclair and Biafine (trolamine/sodium alginate, OrthoNeutrogena) as FDA 510(k) devices means these products can be used in any age and in pregnant patients.
However, he says, "The problem is that because they're considered devices and not drugs, they're not covered by most prescription insurance plans."
A place for probiotics?
As for probiotics, Dr. Gilliam says that while studies suggest they may be helpful in treating AD (Arch Dis Child. 2005 Sep;90[9]:892-897. Epub 2005 Apr 29), she reserves them as a backup for patients who already are using maximal topical therapy and have motivated parents.
"The issue is where does one get them, and how does one practically recommend them to patients? They're available at health food stores, but it can be difficult to ensure that patients get the correct formulation and dose," Dr. Gilliam says.
Overall, she says, "The jury's still out in terms of how effective they are, but it can't hurt to try them."
Disclosures: Dr. Kircik serves as a consultant, investigator and speaker for OrthoNeutrogena, Steifel, Novartis and Astellas. Dr. Gilliam reports no financial interests relevant to this article.
For more information:
Leung DY et al. Ann Allergy Asthma Immunol. 1997 Sep;79(3):197-211; National Institute of Arthritis
and Musculoskeletal Diseases /NIAMS; Abramovits W. J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93; Barnetson RS, Rogers M. BMJ. 2002 Jun 8;324(7350):1376-9; Palmer CN et al. Nat Genet. 2006 Apr;38(4):441-446. Epub 2006 Mar 19; Braff MH et al. J Invest Dermatol. 2005 Jul;125(1):9-13; Weston S et al. Arch Dis Child. 2005 Sep;90(9):892-897. Epub 2005 Apr 29.
"The prevalence of AD is increasing, and it affects between 10 percent and 17 percent of the total United States population," with 80 percent to 90 percent of patients being diagnosed before age five and about half of them eventually outgrowing it (Ann Allergy Asthma Immunol. 1997 Sep;79(3):197-211), says Leon Kircik, M.D., clinical associate professor of dermatology at Indiana University, Indianapolis.
One in five affected
"More than 15 million patients have symptoms of AD," including 20 percent of American children and infants, he adds.
"And 60 percent of affected infants continue to have symptoms in adulthood (Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93)," Dr. Kircik says.
"Most of the time, patients with AD also suffer from secondary infections," including those caused by community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), Dr. Kircik notes.
Therefore, he says, "I suggest culturing every secondary infection" occurring with AD.
AD also can be a marker for other atopic diseases such as asthma, food allergies, hay fever, allergies and rhinitis, Dr. Kircik asserts.
There's also a theory that if one prevents AD from developing or from becoming severe, one will be able to prevent asthma developing later in life. The concept is called the atopic march (BMJ. 2002 Jun 8;324(7350): 1376-1379), Dr. Kircik explains.
Research inroads
Over the past several years, research into the pathogenesis of AD also has focused on the possibility that patients with this disease have a functional problem with their skin barrier, says Amy E. Gilliam, M.D., assistant clinical professor of pediatrics and dermatology at the University of California, San Francisco.
In particular, she says researchers have shown that this barrier dysfunction in patients with AD correlates with a reduction in ceramides, one of the three key stratum corneum lipids.
"Ceramides may also influence inflammatory responses, in addition to their contribution to effective barrier function," Dr. Gilliam says.
"Another recent development in the understanding of the pathogenesis of AD involves a study showing that there may be a genetic predisposition for AD," she says.
In particular, researchers have shown that an inherited reduction in the expression of filaggrin, a key protein involved in the formation of the skin barrier, is a major predisposing factor in AD (Nat Genet. 2006 Apr;38[4]:441-446. Epub 2006 Mar 19).
"This genetic mutation in filaggrin in affected families further supports the hypothesis that an impaired skin barrier plays a key role in the pathogenesis of AD," Dr. Gilliam says.
Similarly, Dr. Gilliam notes other studies have shown that the skin of patients with AD is deficient in certain antimicrobial peptides, specifically beta defensins and cathelicidins, which contribute to the skin's barrier against infection (J Invest Dermatol. 2005 Jul;125[1]:9-13).
Pharmaceutical armamentarium
In keeping with the foregoing developments, manufacturers have begun offering ceramide-based moisturizing creams and other barrier repair formulations, sources say.
Ceramide-based creams include TriCeram (Osmotics), EpiCeram (Ceragenix) and TriXera (Eau Thermale Avene), while products that have earned Food and Drug Administration (FDA) approval include Atopiclair (Sinclair Pharmaceuticals Ltd./Chester Valley) and Mimyx (PEA, Steifel), Dr. Gilliam says.
"Atopiclair and Mimyx do not contain ceramides, but multiple other agents that have anti-inflammatory and anti-pruritic properties," she tells Dermatology Times.
Both are indicated for the management and relief of itching, burning and pain associated with a variety of inflammatory and allergic dermatoses including atopic and contact dermatitis, Dr. Gilliam explains.
However, she says, "One of the caveats one should consider is that Atopiclair contains shea butter, which is a derivative of shea nut oil," to which patients may be allergic.
Moreover, Dr. Kircik says that in a study that compared Mimyx, Atopiclair and Eucerin (10 percent urea cream, Beiersdorf), "Mimyx decreased transepidermal water loss twice as well as Atopiclair and three times as well as petrolatum."
Overall, Dr. Kircik says, "The treatment of AD is changing."
Originally, he says physicians relied heavily on topical steroids, which are still used, but less frequently due to concerns for side effects such as systemic absorption, HPA suppression, atrophy, telangiectasia formation and tachyphylaxis.
Next, he says, "Everybody jumped on the steroid-sparing agents, namely the topical calcineurin inhibitors Elidel (pimecrolimus, Novartis) and Protopic (tacrolimus, Astellas)."
However, Dr. Kircik says that although dermatologists disagree with the FDA's decision to add black box warnings to these products' labels, "It has affected our prescribing patterns because everybody's afraid medically and legally to use those products on children less than two years old."
On a positive note, he says that the approval of Mimyx, Atopiclair and Biafine (trolamine/sodium alginate, OrthoNeutrogena) as FDA 510(k) devices means these products can be used in any age and in pregnant patients.
However, he says, "The problem is that because they're considered devices and not drugs, they're not covered by most prescription insurance plans."
A place for probiotics?
As for probiotics, Dr. Gilliam says that while studies suggest they may be helpful in treating AD (Arch Dis Child. 2005 Sep;90[9]:892-897. Epub 2005 Apr 29), she reserves them as a backup for patients who already are using maximal topical therapy and have motivated parents.
"The issue is where does one get them, and how does one practically recommend them to patients? They're available at health food stores, but it can be difficult to ensure that patients get the correct formulation and dose," Dr. Gilliam says.
Overall, she says, "The jury's still out in terms of how effective they are, but it can't hurt to try them."
Disclosures: Dr. Kircik serves as a consultant, investigator and speaker for OrthoNeutrogena, Steifel, Novartis and Astellas. Dr. Gilliam reports no financial interests relevant to this article.
For more information:
Leung DY et al. Ann Allergy Asthma Immunol. 1997 Sep;79(3):197-211; National Institute of Arthritis
and Musculoskeletal Diseases /NIAMS; Abramovits W. J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S86-93; Barnetson RS, Rogers M. BMJ. 2002 Jun 8;324(7350):1376-9; Palmer CN et al. Nat Genet. 2006 Apr;38(4):441-446. Epub 2006 Mar 19; Braff MH et al. J Invest Dermatol. 2005 Jul;125(1):9-13; Weston S et al. Arch Dis Child. 2005 Sep;90(9):892-897. Epub 2005 Apr 29.
posted by Madison @ 7:46 AM
