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First sublingual immunotherapy tablet for house dust mite allergic rhinitis may be U.S.-bound
LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.
“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.
The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.
HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.
The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.
Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.
There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.
“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.
Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.
The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.
In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.
“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.
Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.
The trial was sponsored by Merck and presented by a full-time company employee.
LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.
“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.
The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.
HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.
The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.
Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.
There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.
“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.
Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.
The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.
In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.
“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.
Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.
The trial was sponsored by Merck and presented by a full-time company employee.
LOS ANGELES – A sublingual immunotherapy tablet for house dust mite–induced allergic rhinitis achieved clinically meaningful improvement in symptoms along with less use of rescue medications and a favorable safety profile in a pivotal phase III trial, Dr. Hendrik Nolte reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The double-blind, 52-week randomized trial included 1,482 North American adults and adolescents.
“This was the largest clinical trial ever conducted with sublingual therapy in North America, and the first successful North American trial of a house dust mite sublingual immunotherapy tablet. It confirms results from previous large European trials,” noted Dr. Nolte of Merck, which is collaborating with the Danish company ALK in developing this therapy.
The sublingual immunotherapy (SLIT) tablet, known for now as the 12 SQ HDM SLIT-tablet, has been approved by European regulatory authorities for treatment of adults with house dust mite (HDM) allergic rhinitis or HDM allergic asthma. Based upon the positive findings in the phase III U.S. trial, Merck applied in February 2016 to the U.S. Food and Drug Administration for approval of the tablet as a biologic agent in patients aged 12 years or older.
HDM is the most common indoor allergen in the world. Unlike pollen and ragweed allergies, it’s not a seasonal problem. Moreover, HDM-induced allergic rhinitis is associated with increased risk of asthma. Although HDM allergic rhinitis can be treated symptomatically with oral antihistamines and nasal steroids, allergy immunotherapy has the appeal of addressing the underlying disease mechanism and potentially altering the long-term course. SLIT using a highly standardized HDM allergen extract offers a major advantage over traditional allergy immunotherapy via a lengthy program of subcutaneous injections – namely, the convenience of home self-administration.
The primary endpoint in the U.S. pivotal trial was the total combined rhinitis score (TCRS), which is the sum of the daily rhinitis symptom score and the daily rescue medication usage score averaged over the last 8 weeks of the year-long study. The FDA has set the bar for establishing clinically meaningful improvement: it requires demonstration of a reduction in the TCRS of at least 15%, compared with placebo. The 12 SQ HDM SLIT-tablet trial exceeded this standard, achieving a 17% reduction. The study also met its key prespecified secondary endpoints, including a 16% reduction in the daily rhinosinusitis symptom score and an 18% decrease in the daily medication score, compared with placebo.
Participants in the trial had a mean 18-year history of allergic rhinitis with or without conjunctivitis. Seventy-five percent of them were sensitized to other common allergens in addition to HDM, and 31% of subjects had comorbid asthma. The HDM SLIT therapy was equally effective in asthmatics and nonasthmatics, in patients allergic only to HDM and those who were polysensitized, and in subjects with and without conjunctivitis, according to Dr. Nolte.
There were no serious adverse events related to the 12 SQ HDM SLIT-tablet. A total of 9.8% of patients discontinued SLIT because of treatment-emergent adverse events, chiefly mild-to-moderate throat irritation, mouth swelling, or itchiness of the mouth or ears.
“Importantly, these events were very transient. They occurred typically within the first 8 days and lasted 14-67 hours, with a median 1-day duration of rescue medication,” he said.
Symptomatic improvement was typically seen beginning at 8-12 weeks. Adults were free to take the once-daily tablet anytime during the day. The pediatric patients were advised not to do so in the morning because they wouldn’t be under observation while on a school bus.
The tablet is based upon a formulation of allergen extracts from the two major species of HDM: Dermatophagoides pterornyssinus and D. farinae. More than 90% of HDM-sensitized patients are sensitized to both. A highly standardized manufacturing process ensures that the tablet contains 50 mcg of the four major HDM allergens in equal ratio – Der f1, Der p2, Der p1, and Der f 2 – plus other components.
In response to audience questions, Dr. Nolte said the company had tried incorporating an antihistamine into the tablet to block adverse reactions but it didn’t work. Adverse events typically occur within a couple of minutes after taking the tablet, and antihistamines are far too slow-acting to help.
“You can premedicate with antihistamines. We know European investigators and clinicians who are doing it. But I would not recommend it personally, because these tablets are taken at home after the first administration in the office, and I think it’s important that the patient has a good feel for what happens over the following days. There is a potential risk of masking side effects with premedication, which could be a concern,” Dr. Nolte said.
Merck already has two FDA-approved SLIT tablets developed with ALK on the U.S. market: Grastek, for treatment of grass pollen–induced allergic rhinitis in children and adults, and Ragwitek, for ragweed-induced allergic disease in adults.
The trial was sponsored by Merck and presented by a full-time company employee.
AT 2016 AAAAI ANNUAL MEETING
Key clinical point: A safe, effective, and convenient self-administered alternative to allergy shots or symptomatic medications for house dust mite allergic rhinitis may be in the works.
Major finding: A once-daily tablet containing house dust mite extract resulted in a clinically meaningful 17% improvement relative to placebo in a score combining symptomatic improvement and reduced use of rescue medications.
Data source: This pivotal phase III, double-blind, 52-week randomized trial included 1,482 North American adults and adolescents with house dust mite–induced allergic rhinitis with or without conjunctivitis.
Disclosures: The trial was sponsored by Merck and presented by a full-time company employee.
No evidence supports hydrolyzed formula over cows’ milk for allergy prevention
Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.
A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.
The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.
The researchers suggest that guidelines be updated and revised to reflect these new findings.
“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.
Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)
Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.
A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.
The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.
The researchers suggest that guidelines be updated and revised to reflect these new findings.
“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.
Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)
Findings on the use of hydrolyzed formula in place of standard cows’ milk formula to prevent allergy in high-risk infants do not support current guidelines, according to Dr. Robert J Boyle of Imperial College London and his associates.
A review and meta-analysis were performed on 28 randomized control trials, 6 quasirandomized trials, and 3 controlled clinical trials describing allergic or autoimmune outcomes, with more than 19,000 participants. Among 13 studies reporting on the risk of food allergy, no significant difference was found in the risk of any food allergy with partially hydrolyzed formula (risk ratio, 1.73; 95% confidence interval, 0.79-3.80) and extensively hydrolyzed formula (RR, 0.86; CI, 0.26-2.82), compared with standard formula at age 0-4 years, and for extensively hydrolyzed formula at age 5-14 years.
The review also examined and found no significant evidence favoring the use of hydrolyzed formula in place of standard cows’ milk formula to avert the risk of eczema, wheeze, allergic rhinitis, or type 1 diabetes mellitus.
The researchers suggest that guidelines be updated and revised to reflect these new findings.
“We found no consistent evidence to support the current recommendations and found evidence of publication bias, methodological biases, and conflict of interest in those studies reporting allergic outcomes,” Dr. Boyle and his associates concluded. “We suggest that any future trials on hydrolyzed formula should be prospectively registered, independently funded, and include adequate oversight to ensure that they do not negatively impact on breastfeeding in study participants”.
Read the full study at the British Medical Journal (doi: 10.1136/bmj.i974)
FROM BRITISH MEDICAL JOURNAL
Diet and Atopic Dermatitis
Atopic dermatitis (AD) is the leading diagnosis among pediatric dermatologists,1 and this condition is commonly seen worldwide by dermatologists and allergists.2 There is a widespread misconception held by many patients and their guardians who believe that AD is caused by a food allergy.3 Although AD is related to and part of the atopic complex of disorders associated with food allergies, the role of diet in AD is not well defined. Previously it was recommended to delay early exposure to foods, but now it is recommended to do the opposite in certain situations. In fact, delaying exposure to certain types of foods can increase the likelihood of food allergies (eg, early exposure to peanut butter lowers the statistical chance of developing peanut allergies). This article reviews recent data on the role of diet in AD regarding disease activity as well as new and emerging data on dietary modifications for prevention and intervention. Emerging data on the relationship between AD and food allergies also are presented.
Pathogenesis of AD
The skin barrier plays a vital role in the prevention of pathogens, allergen exposure, and sensitization. There is no solitary root cause of AD, rather it is a combination of inflammation and barrier dysfunction associated with allergic diathesis (eg, atopy). Many patients with AD, especially those with persistent disease, have an intrinsic barrier dysfunction as part of the root cause of their illness, which may be caused by genetically mediated filaggrin defects or alternative barrier dysfunction such as decreased ceramide content that predisposes to percutaneous and mucosal sensitization.4,5 Another source of percutaneous exposure to allergens is macroscopic breaks in the skin caused by scratching, which allows dendritic termini of Langerhans cells to be exposed to percutaneous antigens4,6 through binding to high-affinity IgE receptors.
Langerhans cells exposed to allergens can trigger either an immediate or delayed-type (type I or type II) reaction (sensitization phase) in the lymph node causing inflammatory activation (elicitation). Inflammatory activity in AD is broad and complex and includes the release of IL-4, elevated IgE levels, and eosinophilia, which trigger the helper T cell TH2 and TH17 cascade of cytokines, including IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-17α, tumor necrosis factor α, and IFN-γ,7-9 with the latter worsening barrier defect via downregulation of intercellular substances (eg, filaggrin) and intercellular adhesion expression (eg, claudin 1).6,7,10
Atopic dermatitis does not exist in isolation. The barrier dysfunction associated with AD allows for sensitization to allergens, including those found in food and/or the environment. The atopic march, which occurs via barrier abnormalities facilitating sensitization, can result in further atopy, such as food allergies, environmental allergies, asthma, and eosinophilic esophagitis.11
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AD and Food Allergies
Many patients and guardians believe AD is caused by a food allergy and that diet restrictions will resolve the disease. Although the latter is not true, in reality many patients with AD do have food allergies. Approximately 40% of infants and young children with moderate to severe AD and 8% of the general population of children will manifest a specific IgE-based food allergy. Food-specific IgE can be triggered or exacerbated by AD through the induction of hives, cutaneous activation of mast cells, increased “spontaneous” basophil histamine release, and food-related lymphocyte-proliferative responses measurable by food patch testing.12 Allergists generally recommend avoidance of or use of heavily denatured food (in the case of a milk/egg allergy) in the setting of documented IgE-mediated allergens.13 Food allergies in AD can manifest with flares, hives, pruritus, and/or other cutaneous symptoms in the absence of flaring AD disease.
Guidelines from the American Academy of Dermatology (AAD)(Table) for the management of AD have recently recommended testing for food allergies in children younger than 5 years who have intractable AD or known food-induced reactions.14 This technique will largely identify children at risk for anaphylaxis but may not yield information contributing to AD improvement. Furthermore, withdrawal of allergens with known IgE-mediated response was classified by the AAD as having consistent good-quality patient-oriented evidence, and asking about allergic reactions as well as acting on a reported allergic history had inconsistent or limited-quality patient-oriented evidence. It is believed that atopy can progress, or march, into a food and/or environmental allergy at any point in life; therefore, testing for a food allergy should be considered in all patients with recent onset of severe and/or persistent AD and/or food-aggravated AD due to a lifetime risk of sensitization.14,15 A food introduction plan may require collaboration with an allergist, especially in high-risk patients (eg, those with known food reactions, family history of food allergies, severe atopy).
Prevention of AD Through Dietary Modification
The National Institute of Allergy and Infectious Diseases consensus group published guidelines on food allergies that affect AD management, including avoidance of proven allergens but not random elimination of food allergens in AD; the group identifies AD and family history of AD as risk factors for food allergies.16 The best data in support of avoidance of documented food allergens to reduce AD severity has been found for egg white allergy and avoidance. Active egg allergy also is linked to staphylococcal superantigen IgE sensitizations,17 but the reason for the link is not yet clear. For the pediatric population, exclusive breastfeeding until 4 to 6 months of age and introduction of solids within the first 4 to 6 months as well as avoidance of maternal dietary restriction during pregnancy and lactation was further endorsed, with use of hydrolyzed formulas as an alternative to exclusive breastfeeding in infants who are not exclusively breastfed (cost permitting).16,18
A Cochrane review of maternal dietary restrictions during pregnancy found no benefit of maternal prenatal dietary restriction on AD prevalence in the first 18 months of life but did note an association with lower mean gestational weight.19
There is currently an effort to produce foods, such as soybeans and corn, that are genetically modified to reduce exposure to the allergenic component, but it is possible that when large-scale challenges occur, these foods also will be allergenic.20,21 In the case of a modified apple, some promising reduction in allergy symptoms has been reported.22 Although genetically modified foods may benefit children with food allergies in the future, they are a source of some controversy.
Complementary and Alternative Medicine
The AAD guidelines do not recommend complementary and alternative medicine (CAM) to treat AD,14 but it remains a commonly used therapy in the United States. A 2014 analysis of data from the 2007 US-based national health interview survey of 9417 children (age range, 0–17 years) demonstrated that 46.9% of children used 1 or more CAM, of which 0.99% used CAM specifically for AD. In this study, herbal therapy, vitamins, homeopathy, diet, and movement techniques were associated with increased prevalence of AD.23 Although some herbals have been shown to be beneficial in AD,24 hepatotoxicity has been reported with some herbal therapies.25 Complementary techniques with evidence-based support include massage therapy,26 relocation to an alternative climate, acupuncture that rivals cetirizine in efficacy, and supportive nutritional advice.24,27
Factors Affecting the Incidence of AD
Atopic dermatitis is of greater prevalence in children in developed wealthy nations such as the United States, supporting the role of enhanced hygiene and overall good health through vaccination as a possible contributor to the rise in AD prevalence in the last 4 decades.28,29 Alternatively, viruses such as respiratory syncytial virus may trigger AD, suggesting vaccination against the virus may reduce the risk for AD.30 Overall, vaccination improves life expectancy and should be conducted on schedule without reservation. Other aspects of hygiene that could conceptually affect prevalence of AD are raw food ingestion and the effects of foodborne microbes on the intestinal microbiome in relationship to AD development. Probiotics have been tested for this purpose.
Probiotics and prebiotics have been theorized to work through a reduction in inflammation; these agents have some evidence in their favor, but they were not endorsed in the AAD guidelines14 despite showing promise in meta-analysis. In particular prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus shows promise.31-33 Food elimination diets and supplements including vitamin D, selenium, fish oil, borage oil, and zinc were not found to be beneficial and were not recommended in the AAD guidelines.14,34
Percutaneous exposure to peanuts, possibly in household dust, may be the mechanism of peanut sensitization in AD27 via an inherent adjuvant effect of peanut protein.28 The recent LEAP (Learning Early About Peanut Allergy) trial randomized 530 infants aged 4 to 11 months to peanut-avoidant versus peanut-exposed diets for 60 months. The results showed statistically reduced (approximately one-twelfth of the risk) peanut allergy even in infants known to be sensitized (approximately one-third of the risk).35 It is now recommended in countries with a high prevalence of peanut allergies to introduce peanuts to an infant’s diet between 4 and 11 months of age (evidence level 1 [highest level of evidence]), with referral to an allergist for introduction in known sensitization cases and severe AD.36 In the setting of known or documented peanut allergy and for evaluation of potential food allergies, an allergist should be consulted.
Other interventions have been described as promising in mouse models. Those supplements include Lithospermum erythrorhizon,37Platycodon grandiflorus,38Hypsizygus marmoreous,39 fortified ginseng extract,40 polyunsaturated fatty acids,41 and galactooligosaccharide.42 Prebiotic oligosaccharides also are promising for early prevention of AD symptoms in infants, but otherwise these agents have remained largely untested in AD.43 None of these therapies have been endorsed by the AAD, and the long-term safety and efficacy in humans remains to be proven.
Risks of Dietary Restriction
Dietary restrictions in treating AD can have negative consequences, including reduced birth weight when initiated in pregnancy,19 osteomalacia from vitamin D deficiency,44 and nutritional deficiencies (eg, calcium, phosphorus, iron, vitamin K, vitamin D, zinc, vitamin A, B1, B2, B6, niacin, cholesterol, and/or vitamin C deficiencies).45 Excess dietary intake of vegetables in individuals with extensive food allergies can result in carotenemia.46 Protein-restricted diets from use of rice milk or dietary protein restriction can result in kwashiorkorlike protein malnutrition and marasmus.47-49 Nutritional counseling and/or supplementation is recommended for patients with food-restricted diets.
Avoiding Fragrance in Food
Food intolerance often is reported by AD patients. In allergies, food intolerance refers to side effects such as gastrointestinal symptoms; in dermatology, food intolerance can include itching, systemic flares of allergic contact dermatitis (eg, fragrance allergy), or true IgE-mediated allergies such as oral allergy syndrome. Oral allergy syndrome (pollen-food allergy syndrome) is an epitope-spread phenomenon related to an allergy to tree pollen, causing broad allergy to specific groups of fruits and nuts.50 Food triggers in AD include kiwi, milk, apple, tomato, citrus fruits, tree nuts, and peanuts. Oral allergy syndrome is common in food-sensitive AD patients (51.2%) followed by gastrointestinal symptoms (23.5%) and worsening AD (11.4%).51 Sensitization to fragrance can cross-react with foods (eg, balsam of Peru and tomatoes).52 A tomato allergy can be detected either by a skin-prick test or a food patch test in this setting.53 An allergist should be consulted if oral allergy syndrome is suspected.
Conclusion
Food allergies are more common in AD patients and patients should be referred to an allergist for evaluation and management. Strict dietary practice is not recommended, while avoiding proven food allergens in AD could be beneficial. Dermatologists should be aware that patients with dietary restrictions may lack key nutrients, manifesting with nutritional deficiencies in the skin; therefore, nutrition counseling may be needed in the most severe AD/allergy patients. This field is evolving; therefore, ongoing study and evaluation of interventions as they relate to AD will be needed to assess best practices for diet in AD over time.
1. Schachner L, Ling NS, Press S. A statistical analysis of a pediatric dermatology clinic. Pediatr Dermatol. 1983;1:157-164.
2. Kiprono SK, Muchunu JW, Masenga JE. Skin diseases in pediatric patients attending a tertiary dermatology hospital in Northern Tanzania: a cross-sectional study. BMC Dermatol. 2015;15:16.
3. Wensink M, Timmer C, Brand PL. Atopic dermatitis in infants not caused by food allergy [in Dutch]. Ned Tijdschr Geneeskd. 2008;152:4-9.
4. De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol. 2012;132(3, pt 2):949-963.
5. Margolis DJ, Apter AJ, Gupta J, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol. 2012;130:912-917.
6. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. 2009;129:320-322.
7. Batista DI, Perez L, Orfali RL, et al. Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol. 2015;29:1091-1095.
8. Kondo H, Ichikawa Y, Imokawa G. Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol. 1998;28:769-779.
9. Correa da Rosa J, Malajian D, Shemer A, et al. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135:712-720.
10. Paller AS. Latest approaches to treating atopic dermatitis. Chem Immunol Allergy. 2012;96:132-140.
11. Cianferoni A, Spergel J. Eosinophilic esophagitis: a comprehensive review [published online July 22, 2015]. Clin Rev Allergy Immunol. doi:10.1111/all.12846.
12. Sicherer SH, Sampson HA. Food hypersensitivity and atopic dermatitis; pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol. 1999;104(3, pt 2):S114-S122.
13. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133:291-307.
14. Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: section 4. prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2014;71:1218-1233.
15. Marenholz I, Rivera VA, Esparza-Gordillo J, et al. Association screening in the epidermal differentiation complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema. J Invest Dermatol. 2011;131:1644-1649.
16. Burks AW, Jones SM, Boyce JA, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics. 2011;128:955-965.
17. Ong PY. Association between egg and staphylococcal superantigen IgE sensitizations in atopic dermatitis. Allergy Asthma Proc. 2014;35:346-348.
18. Botteman M, Detzel P. Cost-effectiveness of partially hydrolyzed whey protein formula in the primary prevention of atopic dermatitis in high-risk urban infants in Southeast Asia. Ann Nutr Metab. 2015;66(suppl 1):26-32.
19. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Cochrane Database Syst Rev. 2012;9:CD000133.
20. Yum HY, Lee SY, Lee KE, et al. Genetically modified and wild soybeans: an immunologic comparison. Allergy Asthma Proc. 2005;26:210-216.
21. Mathur C, Kathuria PC, Dahiya P, et al. Lack of detectable allergenicity in genetically modified maize containing “Cry” proteins as compared to native maize based on in silico & in vitro analysis. PLoS One. 2015;10:e0117340.
22. Dubois AE, Pagliarani G, Brouwer RM, et al. First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar [published online July 24, 2015]. Allergy. 2015;70:1406-1412.
23. Silverberg JI, Lee-Wong M, Silverberg NB. Complementary and alternative medicines and childhood eczema: a US population-based study. Dermatitis. 2014;25:246-254.
24. Pfab F, Schalock PC, Napadow V, et al. Complementary integrative approach for treating pruritus. Dermatol Ther. 2013;26:149-156.
25. Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol. 2015;89:851-865.
26. Schachner L, Field T, Hernandez-Reif M, et al. Atopic dermatitis symptoms decreased in children following massage therapy. Pediatr Dermatol. 1998;15:390-395.
27. Pfab F, Schalock PC, Napadow V, et al. Acupuncture for allergic disease therapy–the current state of evidence. Expert Rev Clin Immunol. 2014;10:831-841.
28. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132:1132-1138.
29. Silverberg JI, Norowitz KB, Kleiman E, et al. Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: a case-control study. J Allergy Clin Immunol. 2010;126:300-305.
30. Welliver RC, Wong DT, Sun M, et al. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med. 1981;305:841-846.
31. Foolad N, Brezinski EA, Chase EP, et al. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol. 2013;149:350-355.
32. Kalliomäki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357:1076-1079.
33. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol. 2007;119:184-191.
34. Bronsnick T, Murzaku EC, Rao BK. Diet in dermatology: part I: atopic dermatitis, acne, and nonmelanoma skin cancer. J Am Acad Dermatol. 2014;71:1039.e1-1039.e12.
35. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
36. Fleischer DM, Sicherer S, Greenhawt M, et al. Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants [published online October 2015]. Allergy. 2015;70:1193-1195.
37. Kim J, Cho Y. Gromwell (Lithospermum erythrorhizon) supplementation enhances epidermal levels of cera-mides, glucosylceramides, β-glucocerebrosidase, and acidicsphingomyelinase in NC/Nga mice. J Med Food. 2013;16:927-933.
38. Choi JH, Jin SW, Han EH, et al. Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1. Phytomedicine. 2014;21:1053-1061.
39. Kim T, Park K, Jung HS, et al. Evaluation of anti-atopic dermatitis activity of Hypsizigus marmoreus extract. Phytother Res. 2014;28:1539-1546.
40. Kim JR, Choi J, Kim J, et al. 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol-fortified ginseng extract attenuates the development of atopic dermatitis-like symptoms in NC/Nga mice. J Ethnopharmacol. 2014;151:365-371.
41. Weise C, Ernst D, van Tol EA, et al. Dietary polyunsaturated fatty acids and non-digestible oligosaccharides reduce dermatitis in mice. Pediatr Allergy Immunol. 2013;24:361-367.
42. Tanabe S, Hochi S. Oral administration of a galactooligosaccharide preparation inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice. Int J Mol Med. 2010;25:331-336.
43. Arslanoglu S, Moro GE, Boehm G, et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life. J Biol Regul Homeost Agents. 2012;26(3 suppl):49-59.
44. Shikino K, Ikusaka M, Yamashita T. Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis [published online July 4, 2014] . BMJ Case Rep.
45. Kim J, Kwon J, Noh G, et al. The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract. 2013;7:488-494.
46. Silverberg NB, Lee-Wong M. Generalized yellow discoloration of the skin. Cutis. 2014;93:E11-E12.
47. Hon KL, Nip SY, Cheung KL. A tragic case of atopic eczema: malnutrition and infections despite multivitamins and supplements. Iran J Allergy Asthma Immunol. 2012;11:267-270.
48. Diamanti A, Pedicelli S, D’Argenio P, et al. Iatrogenic kwashiorkor in three infants on a diet of rice beverages. Pediatr Allergy Immunol. 2011;22:878-879.
49. Pillai K, Acharya S. Iatrogenic kwashiorkar. Indian Pediatr. 2010;47:540-541.
50. Price A, Ramachandran S, Smith GP, et al. Oral allergy syndrome (pollen-food allergy syndrome). Dermatitis. 2015;26:78-88.
51. Mattila L, Kilpeläinen M, Terho EO, et al. Food hypersensitivity among Finnish university students: association with atopic diseases. Clin Exp Allergy. 2003;33:600-606.
52. Paulsen E, Christensen LP, Andersen KE. Tomato contact dermatitis. Contact Dermatitis. 2012;67:321-327.
53. Di Leo E, Nettis E, Cardinale F, et al. Tomato atopy patch test in adult atopic dermatitis: diagnostic value and comparison among different methods. Allergy. 2009;64:659-663.
Atopic dermatitis (AD) is the leading diagnosis among pediatric dermatologists,1 and this condition is commonly seen worldwide by dermatologists and allergists.2 There is a widespread misconception held by many patients and their guardians who believe that AD is caused by a food allergy.3 Although AD is related to and part of the atopic complex of disorders associated with food allergies, the role of diet in AD is not well defined. Previously it was recommended to delay early exposure to foods, but now it is recommended to do the opposite in certain situations. In fact, delaying exposure to certain types of foods can increase the likelihood of food allergies (eg, early exposure to peanut butter lowers the statistical chance of developing peanut allergies). This article reviews recent data on the role of diet in AD regarding disease activity as well as new and emerging data on dietary modifications for prevention and intervention. Emerging data on the relationship between AD and food allergies also are presented.
Pathogenesis of AD
The skin barrier plays a vital role in the prevention of pathogens, allergen exposure, and sensitization. There is no solitary root cause of AD, rather it is a combination of inflammation and barrier dysfunction associated with allergic diathesis (eg, atopy). Many patients with AD, especially those with persistent disease, have an intrinsic barrier dysfunction as part of the root cause of their illness, which may be caused by genetically mediated filaggrin defects or alternative barrier dysfunction such as decreased ceramide content that predisposes to percutaneous and mucosal sensitization.4,5 Another source of percutaneous exposure to allergens is macroscopic breaks in the skin caused by scratching, which allows dendritic termini of Langerhans cells to be exposed to percutaneous antigens4,6 through binding to high-affinity IgE receptors.
Langerhans cells exposed to allergens can trigger either an immediate or delayed-type (type I or type II) reaction (sensitization phase) in the lymph node causing inflammatory activation (elicitation). Inflammatory activity in AD is broad and complex and includes the release of IL-4, elevated IgE levels, and eosinophilia, which trigger the helper T cell TH2 and TH17 cascade of cytokines, including IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-17α, tumor necrosis factor α, and IFN-γ,7-9 with the latter worsening barrier defect via downregulation of intercellular substances (eg, filaggrin) and intercellular adhesion expression (eg, claudin 1).6,7,10
Atopic dermatitis does not exist in isolation. The barrier dysfunction associated with AD allows for sensitization to allergens, including those found in food and/or the environment. The atopic march, which occurs via barrier abnormalities facilitating sensitization, can result in further atopy, such as food allergies, environmental allergies, asthma, and eosinophilic esophagitis.11
|
AD and Food Allergies
Many patients and guardians believe AD is caused by a food allergy and that diet restrictions will resolve the disease. Although the latter is not true, in reality many patients with AD do have food allergies. Approximately 40% of infants and young children with moderate to severe AD and 8% of the general population of children will manifest a specific IgE-based food allergy. Food-specific IgE can be triggered or exacerbated by AD through the induction of hives, cutaneous activation of mast cells, increased “spontaneous” basophil histamine release, and food-related lymphocyte-proliferative responses measurable by food patch testing.12 Allergists generally recommend avoidance of or use of heavily denatured food (in the case of a milk/egg allergy) in the setting of documented IgE-mediated allergens.13 Food allergies in AD can manifest with flares, hives, pruritus, and/or other cutaneous symptoms in the absence of flaring AD disease.
Guidelines from the American Academy of Dermatology (AAD)(Table) for the management of AD have recently recommended testing for food allergies in children younger than 5 years who have intractable AD or known food-induced reactions.14 This technique will largely identify children at risk for anaphylaxis but may not yield information contributing to AD improvement. Furthermore, withdrawal of allergens with known IgE-mediated response was classified by the AAD as having consistent good-quality patient-oriented evidence, and asking about allergic reactions as well as acting on a reported allergic history had inconsistent or limited-quality patient-oriented evidence. It is believed that atopy can progress, or march, into a food and/or environmental allergy at any point in life; therefore, testing for a food allergy should be considered in all patients with recent onset of severe and/or persistent AD and/or food-aggravated AD due to a lifetime risk of sensitization.14,15 A food introduction plan may require collaboration with an allergist, especially in high-risk patients (eg, those with known food reactions, family history of food allergies, severe atopy).
Prevention of AD Through Dietary Modification
The National Institute of Allergy and Infectious Diseases consensus group published guidelines on food allergies that affect AD management, including avoidance of proven allergens but not random elimination of food allergens in AD; the group identifies AD and family history of AD as risk factors for food allergies.16 The best data in support of avoidance of documented food allergens to reduce AD severity has been found for egg white allergy and avoidance. Active egg allergy also is linked to staphylococcal superantigen IgE sensitizations,17 but the reason for the link is not yet clear. For the pediatric population, exclusive breastfeeding until 4 to 6 months of age and introduction of solids within the first 4 to 6 months as well as avoidance of maternal dietary restriction during pregnancy and lactation was further endorsed, with use of hydrolyzed formulas as an alternative to exclusive breastfeeding in infants who are not exclusively breastfed (cost permitting).16,18
A Cochrane review of maternal dietary restrictions during pregnancy found no benefit of maternal prenatal dietary restriction on AD prevalence in the first 18 months of life but did note an association with lower mean gestational weight.19
There is currently an effort to produce foods, such as soybeans and corn, that are genetically modified to reduce exposure to the allergenic component, but it is possible that when large-scale challenges occur, these foods also will be allergenic.20,21 In the case of a modified apple, some promising reduction in allergy symptoms has been reported.22 Although genetically modified foods may benefit children with food allergies in the future, they are a source of some controversy.
Complementary and Alternative Medicine
The AAD guidelines do not recommend complementary and alternative medicine (CAM) to treat AD,14 but it remains a commonly used therapy in the United States. A 2014 analysis of data from the 2007 US-based national health interview survey of 9417 children (age range, 0–17 years) demonstrated that 46.9% of children used 1 or more CAM, of which 0.99% used CAM specifically for AD. In this study, herbal therapy, vitamins, homeopathy, diet, and movement techniques were associated with increased prevalence of AD.23 Although some herbals have been shown to be beneficial in AD,24 hepatotoxicity has been reported with some herbal therapies.25 Complementary techniques with evidence-based support include massage therapy,26 relocation to an alternative climate, acupuncture that rivals cetirizine in efficacy, and supportive nutritional advice.24,27
Factors Affecting the Incidence of AD
Atopic dermatitis is of greater prevalence in children in developed wealthy nations such as the United States, supporting the role of enhanced hygiene and overall good health through vaccination as a possible contributor to the rise in AD prevalence in the last 4 decades.28,29 Alternatively, viruses such as respiratory syncytial virus may trigger AD, suggesting vaccination against the virus may reduce the risk for AD.30 Overall, vaccination improves life expectancy and should be conducted on schedule without reservation. Other aspects of hygiene that could conceptually affect prevalence of AD are raw food ingestion and the effects of foodborne microbes on the intestinal microbiome in relationship to AD development. Probiotics have been tested for this purpose.
Probiotics and prebiotics have been theorized to work through a reduction in inflammation; these agents have some evidence in their favor, but they were not endorsed in the AAD guidelines14 despite showing promise in meta-analysis. In particular prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus shows promise.31-33 Food elimination diets and supplements including vitamin D, selenium, fish oil, borage oil, and zinc were not found to be beneficial and were not recommended in the AAD guidelines.14,34
Percutaneous exposure to peanuts, possibly in household dust, may be the mechanism of peanut sensitization in AD27 via an inherent adjuvant effect of peanut protein.28 The recent LEAP (Learning Early About Peanut Allergy) trial randomized 530 infants aged 4 to 11 months to peanut-avoidant versus peanut-exposed diets for 60 months. The results showed statistically reduced (approximately one-twelfth of the risk) peanut allergy even in infants known to be sensitized (approximately one-third of the risk).35 It is now recommended in countries with a high prevalence of peanut allergies to introduce peanuts to an infant’s diet between 4 and 11 months of age (evidence level 1 [highest level of evidence]), with referral to an allergist for introduction in known sensitization cases and severe AD.36 In the setting of known or documented peanut allergy and for evaluation of potential food allergies, an allergist should be consulted.
Other interventions have been described as promising in mouse models. Those supplements include Lithospermum erythrorhizon,37Platycodon grandiflorus,38Hypsizygus marmoreous,39 fortified ginseng extract,40 polyunsaturated fatty acids,41 and galactooligosaccharide.42 Prebiotic oligosaccharides also are promising for early prevention of AD symptoms in infants, but otherwise these agents have remained largely untested in AD.43 None of these therapies have been endorsed by the AAD, and the long-term safety and efficacy in humans remains to be proven.
Risks of Dietary Restriction
Dietary restrictions in treating AD can have negative consequences, including reduced birth weight when initiated in pregnancy,19 osteomalacia from vitamin D deficiency,44 and nutritional deficiencies (eg, calcium, phosphorus, iron, vitamin K, vitamin D, zinc, vitamin A, B1, B2, B6, niacin, cholesterol, and/or vitamin C deficiencies).45 Excess dietary intake of vegetables in individuals with extensive food allergies can result in carotenemia.46 Protein-restricted diets from use of rice milk or dietary protein restriction can result in kwashiorkorlike protein malnutrition and marasmus.47-49 Nutritional counseling and/or supplementation is recommended for patients with food-restricted diets.
Avoiding Fragrance in Food
Food intolerance often is reported by AD patients. In allergies, food intolerance refers to side effects such as gastrointestinal symptoms; in dermatology, food intolerance can include itching, systemic flares of allergic contact dermatitis (eg, fragrance allergy), or true IgE-mediated allergies such as oral allergy syndrome. Oral allergy syndrome (pollen-food allergy syndrome) is an epitope-spread phenomenon related to an allergy to tree pollen, causing broad allergy to specific groups of fruits and nuts.50 Food triggers in AD include kiwi, milk, apple, tomato, citrus fruits, tree nuts, and peanuts. Oral allergy syndrome is common in food-sensitive AD patients (51.2%) followed by gastrointestinal symptoms (23.5%) and worsening AD (11.4%).51 Sensitization to fragrance can cross-react with foods (eg, balsam of Peru and tomatoes).52 A tomato allergy can be detected either by a skin-prick test or a food patch test in this setting.53 An allergist should be consulted if oral allergy syndrome is suspected.
Conclusion
Food allergies are more common in AD patients and patients should be referred to an allergist for evaluation and management. Strict dietary practice is not recommended, while avoiding proven food allergens in AD could be beneficial. Dermatologists should be aware that patients with dietary restrictions may lack key nutrients, manifesting with nutritional deficiencies in the skin; therefore, nutrition counseling may be needed in the most severe AD/allergy patients. This field is evolving; therefore, ongoing study and evaluation of interventions as they relate to AD will be needed to assess best practices for diet in AD over time.
Atopic dermatitis (AD) is the leading diagnosis among pediatric dermatologists,1 and this condition is commonly seen worldwide by dermatologists and allergists.2 There is a widespread misconception held by many patients and their guardians who believe that AD is caused by a food allergy.3 Although AD is related to and part of the atopic complex of disorders associated with food allergies, the role of diet in AD is not well defined. Previously it was recommended to delay early exposure to foods, but now it is recommended to do the opposite in certain situations. In fact, delaying exposure to certain types of foods can increase the likelihood of food allergies (eg, early exposure to peanut butter lowers the statistical chance of developing peanut allergies). This article reviews recent data on the role of diet in AD regarding disease activity as well as new and emerging data on dietary modifications for prevention and intervention. Emerging data on the relationship between AD and food allergies also are presented.
Pathogenesis of AD
The skin barrier plays a vital role in the prevention of pathogens, allergen exposure, and sensitization. There is no solitary root cause of AD, rather it is a combination of inflammation and barrier dysfunction associated with allergic diathesis (eg, atopy). Many patients with AD, especially those with persistent disease, have an intrinsic barrier dysfunction as part of the root cause of their illness, which may be caused by genetically mediated filaggrin defects or alternative barrier dysfunction such as decreased ceramide content that predisposes to percutaneous and mucosal sensitization.4,5 Another source of percutaneous exposure to allergens is macroscopic breaks in the skin caused by scratching, which allows dendritic termini of Langerhans cells to be exposed to percutaneous antigens4,6 through binding to high-affinity IgE receptors.
Langerhans cells exposed to allergens can trigger either an immediate or delayed-type (type I or type II) reaction (sensitization phase) in the lymph node causing inflammatory activation (elicitation). Inflammatory activity in AD is broad and complex and includes the release of IL-4, elevated IgE levels, and eosinophilia, which trigger the helper T cell TH2 and TH17 cascade of cytokines, including IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-17α, tumor necrosis factor α, and IFN-γ,7-9 with the latter worsening barrier defect via downregulation of intercellular substances (eg, filaggrin) and intercellular adhesion expression (eg, claudin 1).6,7,10
Atopic dermatitis does not exist in isolation. The barrier dysfunction associated with AD allows for sensitization to allergens, including those found in food and/or the environment. The atopic march, which occurs via barrier abnormalities facilitating sensitization, can result in further atopy, such as food allergies, environmental allergies, asthma, and eosinophilic esophagitis.11
|
AD and Food Allergies
Many patients and guardians believe AD is caused by a food allergy and that diet restrictions will resolve the disease. Although the latter is not true, in reality many patients with AD do have food allergies. Approximately 40% of infants and young children with moderate to severe AD and 8% of the general population of children will manifest a specific IgE-based food allergy. Food-specific IgE can be triggered or exacerbated by AD through the induction of hives, cutaneous activation of mast cells, increased “spontaneous” basophil histamine release, and food-related lymphocyte-proliferative responses measurable by food patch testing.12 Allergists generally recommend avoidance of or use of heavily denatured food (in the case of a milk/egg allergy) in the setting of documented IgE-mediated allergens.13 Food allergies in AD can manifest with flares, hives, pruritus, and/or other cutaneous symptoms in the absence of flaring AD disease.
Guidelines from the American Academy of Dermatology (AAD)(Table) for the management of AD have recently recommended testing for food allergies in children younger than 5 years who have intractable AD or known food-induced reactions.14 This technique will largely identify children at risk for anaphylaxis but may not yield information contributing to AD improvement. Furthermore, withdrawal of allergens with known IgE-mediated response was classified by the AAD as having consistent good-quality patient-oriented evidence, and asking about allergic reactions as well as acting on a reported allergic history had inconsistent or limited-quality patient-oriented evidence. It is believed that atopy can progress, or march, into a food and/or environmental allergy at any point in life; therefore, testing for a food allergy should be considered in all patients with recent onset of severe and/or persistent AD and/or food-aggravated AD due to a lifetime risk of sensitization.14,15 A food introduction plan may require collaboration with an allergist, especially in high-risk patients (eg, those with known food reactions, family history of food allergies, severe atopy).
Prevention of AD Through Dietary Modification
The National Institute of Allergy and Infectious Diseases consensus group published guidelines on food allergies that affect AD management, including avoidance of proven allergens but not random elimination of food allergens in AD; the group identifies AD and family history of AD as risk factors for food allergies.16 The best data in support of avoidance of documented food allergens to reduce AD severity has been found for egg white allergy and avoidance. Active egg allergy also is linked to staphylococcal superantigen IgE sensitizations,17 but the reason for the link is not yet clear. For the pediatric population, exclusive breastfeeding until 4 to 6 months of age and introduction of solids within the first 4 to 6 months as well as avoidance of maternal dietary restriction during pregnancy and lactation was further endorsed, with use of hydrolyzed formulas as an alternative to exclusive breastfeeding in infants who are not exclusively breastfed (cost permitting).16,18
A Cochrane review of maternal dietary restrictions during pregnancy found no benefit of maternal prenatal dietary restriction on AD prevalence in the first 18 months of life but did note an association with lower mean gestational weight.19
There is currently an effort to produce foods, such as soybeans and corn, that are genetically modified to reduce exposure to the allergenic component, but it is possible that when large-scale challenges occur, these foods also will be allergenic.20,21 In the case of a modified apple, some promising reduction in allergy symptoms has been reported.22 Although genetically modified foods may benefit children with food allergies in the future, they are a source of some controversy.
Complementary and Alternative Medicine
The AAD guidelines do not recommend complementary and alternative medicine (CAM) to treat AD,14 but it remains a commonly used therapy in the United States. A 2014 analysis of data from the 2007 US-based national health interview survey of 9417 children (age range, 0–17 years) demonstrated that 46.9% of children used 1 or more CAM, of which 0.99% used CAM specifically for AD. In this study, herbal therapy, vitamins, homeopathy, diet, and movement techniques were associated with increased prevalence of AD.23 Although some herbals have been shown to be beneficial in AD,24 hepatotoxicity has been reported with some herbal therapies.25 Complementary techniques with evidence-based support include massage therapy,26 relocation to an alternative climate, acupuncture that rivals cetirizine in efficacy, and supportive nutritional advice.24,27
Factors Affecting the Incidence of AD
Atopic dermatitis is of greater prevalence in children in developed wealthy nations such as the United States, supporting the role of enhanced hygiene and overall good health through vaccination as a possible contributor to the rise in AD prevalence in the last 4 decades.28,29 Alternatively, viruses such as respiratory syncytial virus may trigger AD, suggesting vaccination against the virus may reduce the risk for AD.30 Overall, vaccination improves life expectancy and should be conducted on schedule without reservation. Other aspects of hygiene that could conceptually affect prevalence of AD are raw food ingestion and the effects of foodborne microbes on the intestinal microbiome in relationship to AD development. Probiotics have been tested for this purpose.
Probiotics and prebiotics have been theorized to work through a reduction in inflammation; these agents have some evidence in their favor, but they were not endorsed in the AAD guidelines14 despite showing promise in meta-analysis. In particular prenatal and postnatal (maternal and child) supplementation of Lactobacillus rhamnosus shows promise.31-33 Food elimination diets and supplements including vitamin D, selenium, fish oil, borage oil, and zinc were not found to be beneficial and were not recommended in the AAD guidelines.14,34
Percutaneous exposure to peanuts, possibly in household dust, may be the mechanism of peanut sensitization in AD27 via an inherent adjuvant effect of peanut protein.28 The recent LEAP (Learning Early About Peanut Allergy) trial randomized 530 infants aged 4 to 11 months to peanut-avoidant versus peanut-exposed diets for 60 months. The results showed statistically reduced (approximately one-twelfth of the risk) peanut allergy even in infants known to be sensitized (approximately one-third of the risk).35 It is now recommended in countries with a high prevalence of peanut allergies to introduce peanuts to an infant’s diet between 4 and 11 months of age (evidence level 1 [highest level of evidence]), with referral to an allergist for introduction in known sensitization cases and severe AD.36 In the setting of known or documented peanut allergy and for evaluation of potential food allergies, an allergist should be consulted.
Other interventions have been described as promising in mouse models. Those supplements include Lithospermum erythrorhizon,37Platycodon grandiflorus,38Hypsizygus marmoreous,39 fortified ginseng extract,40 polyunsaturated fatty acids,41 and galactooligosaccharide.42 Prebiotic oligosaccharides also are promising for early prevention of AD symptoms in infants, but otherwise these agents have remained largely untested in AD.43 None of these therapies have been endorsed by the AAD, and the long-term safety and efficacy in humans remains to be proven.
Risks of Dietary Restriction
Dietary restrictions in treating AD can have negative consequences, including reduced birth weight when initiated in pregnancy,19 osteomalacia from vitamin D deficiency,44 and nutritional deficiencies (eg, calcium, phosphorus, iron, vitamin K, vitamin D, zinc, vitamin A, B1, B2, B6, niacin, cholesterol, and/or vitamin C deficiencies).45 Excess dietary intake of vegetables in individuals with extensive food allergies can result in carotenemia.46 Protein-restricted diets from use of rice milk or dietary protein restriction can result in kwashiorkorlike protein malnutrition and marasmus.47-49 Nutritional counseling and/or supplementation is recommended for patients with food-restricted diets.
Avoiding Fragrance in Food
Food intolerance often is reported by AD patients. In allergies, food intolerance refers to side effects such as gastrointestinal symptoms; in dermatology, food intolerance can include itching, systemic flares of allergic contact dermatitis (eg, fragrance allergy), or true IgE-mediated allergies such as oral allergy syndrome. Oral allergy syndrome (pollen-food allergy syndrome) is an epitope-spread phenomenon related to an allergy to tree pollen, causing broad allergy to specific groups of fruits and nuts.50 Food triggers in AD include kiwi, milk, apple, tomato, citrus fruits, tree nuts, and peanuts. Oral allergy syndrome is common in food-sensitive AD patients (51.2%) followed by gastrointestinal symptoms (23.5%) and worsening AD (11.4%).51 Sensitization to fragrance can cross-react with foods (eg, balsam of Peru and tomatoes).52 A tomato allergy can be detected either by a skin-prick test or a food patch test in this setting.53 An allergist should be consulted if oral allergy syndrome is suspected.
Conclusion
Food allergies are more common in AD patients and patients should be referred to an allergist for evaluation and management. Strict dietary practice is not recommended, while avoiding proven food allergens in AD could be beneficial. Dermatologists should be aware that patients with dietary restrictions may lack key nutrients, manifesting with nutritional deficiencies in the skin; therefore, nutrition counseling may be needed in the most severe AD/allergy patients. This field is evolving; therefore, ongoing study and evaluation of interventions as they relate to AD will be needed to assess best practices for diet in AD over time.
1. Schachner L, Ling NS, Press S. A statistical analysis of a pediatric dermatology clinic. Pediatr Dermatol. 1983;1:157-164.
2. Kiprono SK, Muchunu JW, Masenga JE. Skin diseases in pediatric patients attending a tertiary dermatology hospital in Northern Tanzania: a cross-sectional study. BMC Dermatol. 2015;15:16.
3. Wensink M, Timmer C, Brand PL. Atopic dermatitis in infants not caused by food allergy [in Dutch]. Ned Tijdschr Geneeskd. 2008;152:4-9.
4. De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol. 2012;132(3, pt 2):949-963.
5. Margolis DJ, Apter AJ, Gupta J, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol. 2012;130:912-917.
6. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. 2009;129:320-322.
7. Batista DI, Perez L, Orfali RL, et al. Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol. 2015;29:1091-1095.
8. Kondo H, Ichikawa Y, Imokawa G. Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol. 1998;28:769-779.
9. Correa da Rosa J, Malajian D, Shemer A, et al. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135:712-720.
10. Paller AS. Latest approaches to treating atopic dermatitis. Chem Immunol Allergy. 2012;96:132-140.
11. Cianferoni A, Spergel J. Eosinophilic esophagitis: a comprehensive review [published online July 22, 2015]. Clin Rev Allergy Immunol. doi:10.1111/all.12846.
12. Sicherer SH, Sampson HA. Food hypersensitivity and atopic dermatitis; pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol. 1999;104(3, pt 2):S114-S122.
13. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133:291-307.
14. Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: section 4. prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2014;71:1218-1233.
15. Marenholz I, Rivera VA, Esparza-Gordillo J, et al. Association screening in the epidermal differentiation complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema. J Invest Dermatol. 2011;131:1644-1649.
16. Burks AW, Jones SM, Boyce JA, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics. 2011;128:955-965.
17. Ong PY. Association between egg and staphylococcal superantigen IgE sensitizations in atopic dermatitis. Allergy Asthma Proc. 2014;35:346-348.
18. Botteman M, Detzel P. Cost-effectiveness of partially hydrolyzed whey protein formula in the primary prevention of atopic dermatitis in high-risk urban infants in Southeast Asia. Ann Nutr Metab. 2015;66(suppl 1):26-32.
19. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Cochrane Database Syst Rev. 2012;9:CD000133.
20. Yum HY, Lee SY, Lee KE, et al. Genetically modified and wild soybeans: an immunologic comparison. Allergy Asthma Proc. 2005;26:210-216.
21. Mathur C, Kathuria PC, Dahiya P, et al. Lack of detectable allergenicity in genetically modified maize containing “Cry” proteins as compared to native maize based on in silico & in vitro analysis. PLoS One. 2015;10:e0117340.
22. Dubois AE, Pagliarani G, Brouwer RM, et al. First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar [published online July 24, 2015]. Allergy. 2015;70:1406-1412.
23. Silverberg JI, Lee-Wong M, Silverberg NB. Complementary and alternative medicines and childhood eczema: a US population-based study. Dermatitis. 2014;25:246-254.
24. Pfab F, Schalock PC, Napadow V, et al. Complementary integrative approach for treating pruritus. Dermatol Ther. 2013;26:149-156.
25. Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol. 2015;89:851-865.
26. Schachner L, Field T, Hernandez-Reif M, et al. Atopic dermatitis symptoms decreased in children following massage therapy. Pediatr Dermatol. 1998;15:390-395.
27. Pfab F, Schalock PC, Napadow V, et al. Acupuncture for allergic disease therapy–the current state of evidence. Expert Rev Clin Immunol. 2014;10:831-841.
28. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132:1132-1138.
29. Silverberg JI, Norowitz KB, Kleiman E, et al. Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: a case-control study. J Allergy Clin Immunol. 2010;126:300-305.
30. Welliver RC, Wong DT, Sun M, et al. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med. 1981;305:841-846.
31. Foolad N, Brezinski EA, Chase EP, et al. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol. 2013;149:350-355.
32. Kalliomäki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357:1076-1079.
33. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol. 2007;119:184-191.
34. Bronsnick T, Murzaku EC, Rao BK. Diet in dermatology: part I: atopic dermatitis, acne, and nonmelanoma skin cancer. J Am Acad Dermatol. 2014;71:1039.e1-1039.e12.
35. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
36. Fleischer DM, Sicherer S, Greenhawt M, et al. Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants [published online October 2015]. Allergy. 2015;70:1193-1195.
37. Kim J, Cho Y. Gromwell (Lithospermum erythrorhizon) supplementation enhances epidermal levels of cera-mides, glucosylceramides, β-glucocerebrosidase, and acidicsphingomyelinase in NC/Nga mice. J Med Food. 2013;16:927-933.
38. Choi JH, Jin SW, Han EH, et al. Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1. Phytomedicine. 2014;21:1053-1061.
39. Kim T, Park K, Jung HS, et al. Evaluation of anti-atopic dermatitis activity of Hypsizigus marmoreus extract. Phytother Res. 2014;28:1539-1546.
40. Kim JR, Choi J, Kim J, et al. 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol-fortified ginseng extract attenuates the development of atopic dermatitis-like symptoms in NC/Nga mice. J Ethnopharmacol. 2014;151:365-371.
41. Weise C, Ernst D, van Tol EA, et al. Dietary polyunsaturated fatty acids and non-digestible oligosaccharides reduce dermatitis in mice. Pediatr Allergy Immunol. 2013;24:361-367.
42. Tanabe S, Hochi S. Oral administration of a galactooligosaccharide preparation inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice. Int J Mol Med. 2010;25:331-336.
43. Arslanoglu S, Moro GE, Boehm G, et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life. J Biol Regul Homeost Agents. 2012;26(3 suppl):49-59.
44. Shikino K, Ikusaka M, Yamashita T. Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis [published online July 4, 2014] . BMJ Case Rep.
45. Kim J, Kwon J, Noh G, et al. The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract. 2013;7:488-494.
46. Silverberg NB, Lee-Wong M. Generalized yellow discoloration of the skin. Cutis. 2014;93:E11-E12.
47. Hon KL, Nip SY, Cheung KL. A tragic case of atopic eczema: malnutrition and infections despite multivitamins and supplements. Iran J Allergy Asthma Immunol. 2012;11:267-270.
48. Diamanti A, Pedicelli S, D’Argenio P, et al. Iatrogenic kwashiorkor in three infants on a diet of rice beverages. Pediatr Allergy Immunol. 2011;22:878-879.
49. Pillai K, Acharya S. Iatrogenic kwashiorkar. Indian Pediatr. 2010;47:540-541.
50. Price A, Ramachandran S, Smith GP, et al. Oral allergy syndrome (pollen-food allergy syndrome). Dermatitis. 2015;26:78-88.
51. Mattila L, Kilpeläinen M, Terho EO, et al. Food hypersensitivity among Finnish university students: association with atopic diseases. Clin Exp Allergy. 2003;33:600-606.
52. Paulsen E, Christensen LP, Andersen KE. Tomato contact dermatitis. Contact Dermatitis. 2012;67:321-327.
53. Di Leo E, Nettis E, Cardinale F, et al. Tomato atopy patch test in adult atopic dermatitis: diagnostic value and comparison among different methods. Allergy. 2009;64:659-663.
1. Schachner L, Ling NS, Press S. A statistical analysis of a pediatric dermatology clinic. Pediatr Dermatol. 1983;1:157-164.
2. Kiprono SK, Muchunu JW, Masenga JE. Skin diseases in pediatric patients attending a tertiary dermatology hospital in Northern Tanzania: a cross-sectional study. BMC Dermatol. 2015;15:16.
3. Wensink M, Timmer C, Brand PL. Atopic dermatitis in infants not caused by food allergy [in Dutch]. Ned Tijdschr Geneeskd. 2008;152:4-9.
4. De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol. 2012;132(3, pt 2):949-963.
5. Margolis DJ, Apter AJ, Gupta J, et al. The persistence of atopic dermatitis and filaggrin (FLG) mutations in a US longitudinal cohort. J Allergy Clin Immunol. 2012;130:912-917.
6. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol. 2009;129:320-322.
7. Batista DI, Perez L, Orfali RL, et al. Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol. 2015;29:1091-1095.
8. Kondo H, Ichikawa Y, Imokawa G. Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response. Eur J Immunol. 1998;28:769-779.
9. Correa da Rosa J, Malajian D, Shemer A, et al. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135:712-720.
10. Paller AS. Latest approaches to treating atopic dermatitis. Chem Immunol Allergy. 2012;96:132-140.
11. Cianferoni A, Spergel J. Eosinophilic esophagitis: a comprehensive review [published online July 22, 2015]. Clin Rev Allergy Immunol. doi:10.1111/all.12846.
12. Sicherer SH, Sampson HA. Food hypersensitivity and atopic dermatitis; pathophysiology, epidemiology, diagnosis, and management. J Allergy Clin Immunol. 1999;104(3, pt 2):S114-S122.
13. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133:291-307.
14. Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: section 4. prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol. 2014;71:1218-1233.
15. Marenholz I, Rivera VA, Esparza-Gordillo J, et al. Association screening in the epidermal differentiation complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema. J Invest Dermatol. 2011;131:1644-1649.
16. Burks AW, Jones SM, Boyce JA, et al. NIAID-sponsored 2010 guidelines for managing food allergy: applications in the pediatric population. Pediatrics. 2011;128:955-965.
17. Ong PY. Association between egg and staphylococcal superantigen IgE sensitizations in atopic dermatitis. Allergy Asthma Proc. 2014;35:346-348.
18. Botteman M, Detzel P. Cost-effectiveness of partially hydrolyzed whey protein formula in the primary prevention of atopic dermatitis in high-risk urban infants in Southeast Asia. Ann Nutr Metab. 2015;66(suppl 1):26-32.
19. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Cochrane Database Syst Rev. 2012;9:CD000133.
20. Yum HY, Lee SY, Lee KE, et al. Genetically modified and wild soybeans: an immunologic comparison. Allergy Asthma Proc. 2005;26:210-216.
21. Mathur C, Kathuria PC, Dahiya P, et al. Lack of detectable allergenicity in genetically modified maize containing “Cry” proteins as compared to native maize based on in silico & in vitro analysis. PLoS One. 2015;10:e0117340.
22. Dubois AE, Pagliarani G, Brouwer RM, et al. First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar [published online July 24, 2015]. Allergy. 2015;70:1406-1412.
23. Silverberg JI, Lee-Wong M, Silverberg NB. Complementary and alternative medicines and childhood eczema: a US population-based study. Dermatitis. 2014;25:246-254.
24. Pfab F, Schalock PC, Napadow V, et al. Complementary integrative approach for treating pruritus. Dermatol Ther. 2013;26:149-156.
25. Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol. 2015;89:851-865.
26. Schachner L, Field T, Hernandez-Reif M, et al. Atopic dermatitis symptoms decreased in children following massage therapy. Pediatr Dermatol. 1998;15:390-395.
27. Pfab F, Schalock PC, Napadow V, et al. Acupuncture for allergic disease therapy–the current state of evidence. Expert Rev Clin Immunol. 2014;10:831-841.
28. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132:1132-1138.
29. Silverberg JI, Norowitz KB, Kleiman E, et al. Association between varicella zoster virus infection and atopic dermatitis in early and late childhood: a case-control study. J Allergy Clin Immunol. 2010;126:300-305.
30. Welliver RC, Wong DT, Sun M, et al. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med. 1981;305:841-846.
31. Foolad N, Brezinski EA, Chase EP, et al. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol. 2013;149:350-355.
32. Kalliomäki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357:1076-1079.
33. Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol. 2007;119:184-191.
34. Bronsnick T, Murzaku EC, Rao BK. Diet in dermatology: part I: atopic dermatitis, acne, and nonmelanoma skin cancer. J Am Acad Dermatol. 2014;71:1039.e1-1039.e12.
35. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
36. Fleischer DM, Sicherer S, Greenhawt M, et al. Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants [published online October 2015]. Allergy. 2015;70:1193-1195.
37. Kim J, Cho Y. Gromwell (Lithospermum erythrorhizon) supplementation enhances epidermal levels of cera-mides, glucosylceramides, β-glucocerebrosidase, and acidicsphingomyelinase in NC/Nga mice. J Med Food. 2013;16:927-933.
38. Choi JH, Jin SW, Han EH, et al. Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1. Phytomedicine. 2014;21:1053-1061.
39. Kim T, Park K, Jung HS, et al. Evaluation of anti-atopic dermatitis activity of Hypsizigus marmoreus extract. Phytother Res. 2014;28:1539-1546.
40. Kim JR, Choi J, Kim J, et al. 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol-fortified ginseng extract attenuates the development of atopic dermatitis-like symptoms in NC/Nga mice. J Ethnopharmacol. 2014;151:365-371.
41. Weise C, Ernst D, van Tol EA, et al. Dietary polyunsaturated fatty acids and non-digestible oligosaccharides reduce dermatitis in mice. Pediatr Allergy Immunol. 2013;24:361-367.
42. Tanabe S, Hochi S. Oral administration of a galactooligosaccharide preparation inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice. Int J Mol Med. 2010;25:331-336.
43. Arslanoglu S, Moro GE, Boehm G, et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the first 5 years of life. J Biol Regul Homeost Agents. 2012;26(3 suppl):49-59.
44. Shikino K, Ikusaka M, Yamashita T. Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis [published online July 4, 2014] . BMJ Case Rep.
45. Kim J, Kwon J, Noh G, et al. The effects of elimination diet on nutritional status in subjects with atopic dermatitis. Nutr Res Pract. 2013;7:488-494.
46. Silverberg NB, Lee-Wong M. Generalized yellow discoloration of the skin. Cutis. 2014;93:E11-E12.
47. Hon KL, Nip SY, Cheung KL. A tragic case of atopic eczema: malnutrition and infections despite multivitamins and supplements. Iran J Allergy Asthma Immunol. 2012;11:267-270.
48. Diamanti A, Pedicelli S, D’Argenio P, et al. Iatrogenic kwashiorkor in three infants on a diet of rice beverages. Pediatr Allergy Immunol. 2011;22:878-879.
49. Pillai K, Acharya S. Iatrogenic kwashiorkar. Indian Pediatr. 2010;47:540-541.
50. Price A, Ramachandran S, Smith GP, et al. Oral allergy syndrome (pollen-food allergy syndrome). Dermatitis. 2015;26:78-88.
51. Mattila L, Kilpeläinen M, Terho EO, et al. Food hypersensitivity among Finnish university students: association with atopic diseases. Clin Exp Allergy. 2003;33:600-606.
52. Paulsen E, Christensen LP, Andersen KE. Tomato contact dermatitis. Contact Dermatitis. 2012;67:321-327.
53. Di Leo E, Nettis E, Cardinale F, et al. Tomato atopy patch test in adult atopic dermatitis: diagnostic value and comparison among different methods. Allergy. 2009;64:659-663.
Practice Points
- Test children younger than 5 years with moderate to severe atopic dermatitis (AD) for food allergies if they have persistently severe AD or known food-induced reactions.
- Food elimination diets are not recommended for management of AD.
- There is not enough evidence supporting the use of complementary and alternative medicine, probiotics/prebiotics, or supplements for the treatment of AD.
AAAAI: Early peanut consumption brings lasting protection from allergy
LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.
“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.
A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.
The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.
In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).
The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.
Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.
These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.
“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.
The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.
“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.
“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”
Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.
The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.
Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).
LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.
LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.
“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.
A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.
The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.
In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).
The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.
Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.
These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.
“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.
The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.
“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.
“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”
Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.
The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.
Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).
LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.
LOS ANGELES – A peanut allergy prevention strategy based upon regular consumption of peanut-containing foods from infancy to age 5 continued to provide protection even after peanut intake was halted for a full year from age 5 to 6, according to new results from an extension of the landmark LEAP trial, known as LEAP-On, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
The impetus for LEAP-On was the investigators’ concern that a period of peanut avoidance might cause loss of the protective state. But that didn’t occur.
“I think there is no doubt that we have prevented peanut allergy so far in these high-risk children. Next, the LEAP-Ad Lib study will tell us whether we’ve prevented it by age 10,” said Dr. Gideon Lack of King’s College London, who headed LEAP-On.
A second major randomized trial known as EAT (Enquiring About Tolerance) presented at the meeting provided further support for early dietary introduction of allergenic foods. EAT differed from LEAP (Learning Early About Peanut Allergy) and LEAP-On in that it ambitiously randomized infants to early introduction or avoidance of not one but six allergenic foods: peanut, cooked egg, cow’s milk, fish, sesame, and wheat. Also, while LEAP and LEAP-On involved roughly 600 infants known to be at very high risk for allergy, EAT was conducted in a general population of 1,303 infants who weren’t at increased risk, all of whom were exclusively breast-fed until the intervention beginning at age 3 months.
The presentation of the LEAP-On and EAT results at the AAAAI annual meeting was a major event marked by the National Institute of Allergy and Infectious Diseases by same-day release of new NIAID-sponsored draft recommendations for the diagnosis and management of food allergies.
In a press conference held at the AAAAI annual meeting to announce the start of a 45-day public comment period for the draft update of the 2010 guidelines, Dr. Daniel Rotrosen, director of NIAID’s division of allergy, immunology and transplantation, said the new guidelines were developed largely in response to the compelling LEAP findings. That trial demonstrated that sustained consumption of peanut starting in infancy resulted in an 81% lower rate of peanut allergy at age 5 years compared to a strategy of peanut avoidance (N Engl J Med. 2015;372:803-13).
The draft guidelines, now available on the NIAID website, represent a sharp departure from the former recommendation that physicians encourage exclusive breastfeeding for the first 6 months of life followed by cautious introduction of other foods. Whereas the former orthodoxy was that delayed introduction of allergenic foods protects against development of food allergy, the new evidence-based concept supported by the LEAP and EAT findings is that just the opposite is true: that is, introduction of such foods during the period of immunologic plasticity in infancy induces tolerance.
Thus, the draft guidelines recommend that infants at high risk for peanut allergy because they have severe eczema and/or egg allergy should have introduction of peanut-containing food at 4-6 months of age to reduce their risk of peanut allergy, preceded by evaluation using peanut-specific IgE or skin prick testing to make sure it’s safe. That age window coincides with well-child visits and vaccination schedules, Dr. Rotrosen noted.
These guidelines represent the consensus of 26 organizations that participated in their development. Among them are the American Academy of Pediatrics, the American Academy of Family Physicians, the American Academy of Dermatology, the American College of Gastroenterology, and AAAAI.
“I expect the new guidelines, when finalized, to be endorsed by the leadership of all the participating organizations,” Dr. Rotrosen said.
The new paradigm will require cultural change, said Dr. James R. Baker Jr., CEO and chief medical officer of Food Allergy Research and Education, a nonprofit organization that provided partial funding for LEAP and LEAP-On.
“I think for a long time we’ve vilified these foods. There’s nothing inherently wrong with their intake, and that’s a message we need to get across to parents and physicians so they can start thinking differently,” he said.
“The good news about these studies is that they show there’s no reason not to do this,” Dr. Baker added. “There’s no harm that comes from the early introduction.”
Dr. Lack, who led the EAT trial, noted that the study didn’t meet it’s primary endpoint of a significantly lower prevalence of food allergy to any of the six intervention foods at age 3 years in the intention-to-treat analysis. But adherence to the demanding EAT early-introduction protocol was a problem. Indeed, only 43% of participants adhered to the study protocol. In a per-protocol analysis restricted to the adherent group, however, early introduction was associated with a highly significant 67% reduction in the relative risk of food allergy at 3 years of age compared to controls. And for the two most prevalent food allergies – to peanut and egg – the relative risk reductions in the early-introduction group were 100% and 75%, respectively.
The EAT results suggest that an effective preventive dose of peanut in infants at least 3 months of age is roughly 2 g of peanut protein per week, equivalent to just under 2 tsp of peanut butter, according to Dr. Lack.
Simultaneously with presentation of the LEAP-On and EAT trials in Los Angeles, the studies were published online at NEJM.org (doi: 10.1056/NEJMoa1514210 for LEAP-ON and 10.1056/NEJMoa1514209 for EAT).
LEAP-On was supported primarily by NIAID. EAT was funded mainly by the UK Foods Standards Agency and the Medical Research Council. Dr. Lack reported receiving grants from those agencies as well as Food Allergy Research and Education.
EXPERT ANALYSIS FROM THE 2016 AAAAI ANNUAL MEETING
Therapies to Improve the Cosmetic Symptoms of Atopic Dermatitis
Atopic dermatitis (AD), more commonly referred to as eczema, is a chronic pruritic inflammatory skin disease that frequently affects both children and adults. Atopic dermatitis is most common in urban and developed countries, with a prevalence of approximately 11% in the United States.1 The pathophysiology of AD is complex and not fully understood, despite the increasing incidence of the disease.2 A myriad of factors, including genetics, defects in the innate and adaptive immune response, and skin barrier abnormalities all contribute to the pathogenesis.3,4 As a result of these abnormalities, patients with AD are more prone to damage from environmental irritants and allergens.
The diagnosis of AD is made clinically based on patient history and visual assessment of the skin.5 Atopic dermatitis follows a chronic and relapsing course characterized by severe pruritus and visible skin changes including xerosis, redness, blistering, oozing, crusting, scaling, thickening, and color change.6,7 Due to the genetic predisposition to make IgE antibodies in response to common environmental and food antigens, patients also may develop allergic rhinitis, asthma, and food-induced anaphylaxis.8,9 Patients also are susceptible to cutaneous viral, fungal, and bacterial infections, the most common of which is an infection with Staphylococcus aureus.10
Atopic dermatitis can have a substantial impact on quality of life, which has been revealed in studies linking chronic skin conditions to depression, impairment of self-esteem, and financial hardship.11 Because skin appearance impacts how a person is initially perceived by others, patients often report feeling self-conscious about their disease and experience teasing or bullying.12 To improve their physical appearance, patients may incur considerable medical expenses. According to 2 population-based studies comprising more than 60,000 adults aged 18 to 85 years, individuals with AD face substantial financial burdens and utilize the health care system more than those without the disease. On average, patients with AD spend $371 to $489 per year on costly out-of-pocket medical expenses and report more absences from work.13
Although there currently is no cure for AD, treatment is aimed at relieving its symptoms and preventing acute exacerbations as well as improving cosmetic appearance to enhance quality of life. Treatment must follow a stepwise approach, which focuses on hydrating the skin, repairing the dysfunctional epithelial barrier, and controlling inflammation. Thus, the standard of care focuses on avoiding skin irritants and triggers along with the use of moisturizers and topical corticosteroids (TCs). In patients with recurring severe disease, topical calcineurin inhibitors, phototherapy, and systemic agents also may be utilized.14
Avoiding Irritants and Triggers
Atopic dermatitis is worsened by skin contact with physical and chemical irritants. Exacerbating factors in AD include exposure to food allergens, dust, emotional stress, detergents, fragranced soaps, textiles, and ingredients in cosmetic products. Patients should be advised to use mild detergents and fragrance-free soaps and to avoid harsh materials such as wool. However, avoidance of specific ingredients in cosmetic products is not as straightforward because manufacturers are not required to disclose certain ingredients. In general, fragrances such as balsam of Peru and cinnamaldehyde, as well as preservatives such as parabens, isothiazolinones, and formaldehyde, should be avoided when selecting cosmetic products. Patients with AD should purchase fragrance-free products that are specifically formulated for sensitive skin. Additionally, patients should not apply makeup if their skin is irritated or oozing, as the flare may worsen.15
Moisturizers
Due to the impaired skin barrier function in patients with AD, regular application of fragrance-free moisturizers is essential to maintain hydration and to reduce xerosis. Various classes of moisturizers may be prescribed (eg, lotions, creams, gels, ointments) based on disease severity and patient preference. Light preparations such as lotions, creams, and gels have a high water content and generally are more appealing from a cosmetic standpoint because they do not create any residue on the skin. However, these options may require more frequent application because they are absorbed quickly. Heavy preparations such as ointments have longer-lasting effects due to their high oil content but tend to be less cosmetically appealing because of their greasiness.16
Although the amount and frequency of application of moisturizers has not been defined, liberal application several times daily is generally advised to minimize xerosis.17 Most physicians recommend applying moisturizer to the skin immediately after bathing to seal in moisture. Some patients prefer to use lotions and creams during the day because these products make the skin feel smooth and reserve the greasier ointments for nighttime application.
Topical Corticosteroids
Prescribed in conjunction with moisturizers, TCs are the mainstay of anti-inflammatory therapy in AD. Topical corticosteroids are classified into 7 groups based on potency, ranging from superpotent (class 1) to least potent (class 7). For acute AD flares, TCs should be applied daily for up to several weeks. Once the inflammation has resolved, it is recommended to apply TCs once to twice weekly to reduce the rate of relapse.18 Despite their effectiveness in the treatment of acute AD flares, TCs have a considerable side-effect profile. Potential adverse effects include skin atrophy, striae, telangiectasia, hypopigmentation, increased hair growth, steroid acne, growth retardation, and Cushing syndrome. Skin atrophy, which is the most common complication associated with TCs, results in shiny transparent skin, allowing for visualization of veins.19,20 Although many of these side effects will resolve after discontinuing the TCs, they are aesthetically displeasing during treatment, making it crucial for physicians to educate their patients on the proper usage of TCs to prevent negative outcomes.
Topical Calcineurin Inhibitors
Topical calcineurin inhibitors (TCIs) are a class of anti-inflammatories that are used to overcome the adverse effects of TCs. They are approved as alternatives to TCs in patients who have failed to respond to other topical treatments as well as those who have developed cutaneous atrophy from the use of TCs or have AD in sensitive areas such as the face, neck, and/or skin folds. Unlike TCs, TCIs do not cause atrophy, striae, or discoloration of the skin, which makes them more desirable from a cosmetic perspective. Their mechanism of action is distinct from TCs in that they inhibit calcineurin-dependent T-cell activation, thus preventing the transcription of inflammatory cytokines.21 Two TCIs are currently available: tacrolimus ointment 0.03% and 0.1% concentrations for moderate to severe AD and pimecrolimus cream 1% for mild to moderate AD.22 Twice-daily application of TCIs is recommended to decrease inflammation and pruritus associated with AD. Studies also have shown that intermittent use of TCIs 3 times weekly can aid in reducing relapses.23-25
The results from clinical trials demonstrate the rapid and continuous effects of both pimecrolimus and tacrolimus. In a controlled long-term study of adults, pimecrolimus provided significant relief of pruritus as soon as day 3 (P<.001).26,27 Pimecrolimus also provides long-term relief by preventing disease progression to flares, which was exemplified in a study (N=713) with no flares in 51% of pimecrolimus patients at 12 months versus 28% in the conventional treatment group (P<.001).28 Similarly, long-term studies of tacrolimus demonstrated an improvement of all symptoms of AD after 1 week of treatment. Maximal improvement was achieved with continued use of tacrolimus, and up to 1 year of tacrolimus use was found to be safe and effective.29,30 Thus, TCIs have been proven to be an effective choice in maintenance therapy for AD and have a good safety profile. The most common adverse effects of TCIs are local skin reactions, such as stinging and burning at the site of application. Rare cases of skin cancer and lymphoma have been reported; however, a causal relationship has yet to be established.31,32
Additional Therapies
Wet wrap therapy is effective for rapid control of flares and in controlling recalcitrant AD. Wet wraps function via several mechanisms; they provide a mechanical barrier against scratching, increase moisture and soften the skin, and enhance absorption of topical medications.33,34 The following method is employed when using wet wraps: an emollient or TC is applied to the area, a tubular bandage soaked in warm water is wrapped over the area, and dry bandages are used to form the outermost layer. Although wet wrap therapy is beneficial in treating AD, it is labor intensive and may require the expertise of a nurse. Thus, unlike other therapies, which patients can easily apply without interfering with their day, wet wraps must be applied at home or in a hospital setting.
Light therapy is another effective method of controlling AD. Although multiple forms of UV phototherapy are beneficial for symptom control in AD, there is no definitive recommendation regarding the specific type of light therapy due to a lack of comparative studies. Natural sunlight, narrowband UVB, broadband UVB, UVA, oral or topical psoralen plus UVA, as well as UVA and UVB can all be utilized in the treatment of AD. However, similar to natural sunlight, artificial light therapy can cause burning, blistering, hyperpigmentation, dark spots, and wrinkles. Because society places a large emphasis on maintaining a youthful appearance, patients may be hesitant to use a treatment that could potentially advance the skin’s aging process. Thus, it is important that this therapy is properly controlled to prevent further skin damage.35-37
When optimal topical regimens and phototherapy have failed to control AD, systemic immunomodulation therapies may be used. Currently, the most commonly used medications are cyclosporine 150 to 300 mg daily, methotrexate 7.5 to 25 mg weekly, mycophenolate mofetil 0.5 to 3 g daily, and azathioprine 1 to 3 mg/kg daily.38,39 Decisions regarding the specific class of drugs should be based on the patient’s AD status, comorbidities, and personal preference.
Conclusion
Atopic dermatitis is a common chronic condition that can occur at any age and cause substantial physical, psychological, social, and/or emotional stress for patients and their families. Although TCs have been the standard of treatment for many years, ongoing concerns regarding their safety have led to the use of TCIs, which overcome some of the drawbacks of steroid therapy. Phototherapy and systemic immunosuppressant therapy are reserved for patients who have not responded to optimal topical therapies. Although several therapeutic avenues exist for patients, there is a need for the development of more effective and safer drugs. Furthermore, cosmetic products created specifically for patients with AD would be beneficial, as patients often struggle to select products that do not cause more harm than good. Given the complexity of the pathogenesis of AD, further research must focus on defining the specific pathways involved in the disease and targeting these pathways with therapies.
1. Shaw TE, Currie GP, Koudelka CW, et al. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131:67-73.
2. Deckers IA, McLean S, Linssen S, et al. Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS One. 2012;7:e39803.
3. Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242:233-246.
4. Peate I. Eczema: causes, symptoms and treatment in the community. Br J Community Nurs. 2011;16:324, 326-331.
5. Williams HC, Burney PG, Pembroke AC, et al. The U.K. Working Party’s diagnostic criteria for atopic dermatitis. III. independent hospital validation. Br J Dermatol. 1994;131:406-416.
6. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
7. Beattie P, Lewis-Jones M. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155:145-151.
8. Spergel JM. From atopic dermatitis to asthma: the atopic march [published online January 22, 2010]. Ann Allergy Asthma Immunol. 2010;105:99-106; quiz 107-109, 117.
9. Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013;62:151-161.
10. Balma-Mena A, Lara-Corrales I, Zeller J, et al. Colonization with community-acquired methicillin-resistant Staphylococcus aureus in children with atopic dermatitis: a cross-sectional study. Int J Dermatol. 2011;50:682-688.
11. Strawser MS, Storch EA, Roberti JW. The Teasing Questionnaire-Revised: measurement of childhood teasing in adults. J Anxiety Disord. 2005;19:780-792.
12. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
13. Silverberg J. Health care utilization, patient costs, and access to care in US adults with eczema: a population-based study. JAMA Dermatol. 2015;151:743-752.
14. Ellis C, Luger T, Abeck D, et al. International Consensus Conference on Atopic Dermatitis II (ICCAD II): clinical update and current treatment strategies. Br J Dermatol. 2003;148(suppl 63):3-10.
15. Kim K. Influences of environmental chemicals on atopic dermatitis. Toxicol Res. 2015;31:89-96.
16. Ridd M, Redmond N, Hollinghurst S, et al. Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial. Trials. 2015;16:304.
17. Hon KL, Ching GK, Leung TF, et al. Estimating emollient usage in patients with eczema. Clin Exp Dermatol. 2010;35:22-26.
18. Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002;147:528-537.
19. Hill CJ, Rostenberg A Jr. Adverse effects from topical steroids. Cutis. 1978;21:624-628.
20. Ruiz-Maldonado R, Zapata G, Lourdes T, et al. Cushing’s syndrome after topical application of corticosteroids. Am J Dis Child. 1982;136:274-275.
21. Grassberger M, Baumruker T, Enz A, et al. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999;141:264-273.
22. Eichenfield L, Wynnis T, Berger T. Guidelines of care for the management of atopic dermatitis: management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116-132.
23. Reitamo S, Harper J, Bos JD, et al. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol. 2004;150:554-562.
24. Ruer-Mulard M, Aberer W, Gunstone A, et al. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2009;26:551-558.
25. Breneman D, Fleischer AB Jr, Abramovits W, et al. Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol. 2008;58:990-999.
26. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream 1% (Elidel) provides significant and rapid relief of pruritus and improves disease control and quality of life in atopic dermatitis in adults. J Invest Dermatol. 2002;119:350.
27. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Dermatology. 2002;205:271-277.
28. Wahn U, Bos JD, Goodfield M, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics. 2002;110(1, pt 1):e2.
29. Kang S, Lucky AW, Pariser D, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol. 2001;44(suppl 1):S58-S64.
30. Reitamo S, Wollenberg A, Schöpf E, et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. the European Tacrolimus Ointment Study Group. Arch Dermatol. 2000;136:999-1006.
31. Frankel HC, Qureshi AA. Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis. Am J Clin Dermatol. 2012;13:113-123.
32. Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol. 2011;165:465-473.
33. Dabade TS, Davis DM, Wetter DA, et al. Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic. J Am Acad Dermatol. 2012;67:100-106.
34. Devillers AC, Oranje AP. Efficacy and safety of ‘wet-wrap’ dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature. Br J Dermatol. 2006;154:579-585.
35. Meduri NB, Vandergriff T, Rasmussen H, et al. Phototherapy in the management of atopic dermatitis: a systematic review. Photodermatol Photoimmunol Photomed. 2007;23:106-112.
36. Clayton TH, Clark SM, Turner D, et al. The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapy. Clin Exp Dermatol. 2007;32:28-33.
37. Jekler J, Larko O. UVB phototherapy of atopic dermatitis. Br J Dermatol. 1988;119:697-705.
38. Roekevisch E, Spuls PI, Kuester D, et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133:429-438.39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
Atopic dermatitis (AD), more commonly referred to as eczema, is a chronic pruritic inflammatory skin disease that frequently affects both children and adults. Atopic dermatitis is most common in urban and developed countries, with a prevalence of approximately 11% in the United States.1 The pathophysiology of AD is complex and not fully understood, despite the increasing incidence of the disease.2 A myriad of factors, including genetics, defects in the innate and adaptive immune response, and skin barrier abnormalities all contribute to the pathogenesis.3,4 As a result of these abnormalities, patients with AD are more prone to damage from environmental irritants and allergens.
The diagnosis of AD is made clinically based on patient history and visual assessment of the skin.5 Atopic dermatitis follows a chronic and relapsing course characterized by severe pruritus and visible skin changes including xerosis, redness, blistering, oozing, crusting, scaling, thickening, and color change.6,7 Due to the genetic predisposition to make IgE antibodies in response to common environmental and food antigens, patients also may develop allergic rhinitis, asthma, and food-induced anaphylaxis.8,9 Patients also are susceptible to cutaneous viral, fungal, and bacterial infections, the most common of which is an infection with Staphylococcus aureus.10
Atopic dermatitis can have a substantial impact on quality of life, which has been revealed in studies linking chronic skin conditions to depression, impairment of self-esteem, and financial hardship.11 Because skin appearance impacts how a person is initially perceived by others, patients often report feeling self-conscious about their disease and experience teasing or bullying.12 To improve their physical appearance, patients may incur considerable medical expenses. According to 2 population-based studies comprising more than 60,000 adults aged 18 to 85 years, individuals with AD face substantial financial burdens and utilize the health care system more than those without the disease. On average, patients with AD spend $371 to $489 per year on costly out-of-pocket medical expenses and report more absences from work.13
Although there currently is no cure for AD, treatment is aimed at relieving its symptoms and preventing acute exacerbations as well as improving cosmetic appearance to enhance quality of life. Treatment must follow a stepwise approach, which focuses on hydrating the skin, repairing the dysfunctional epithelial barrier, and controlling inflammation. Thus, the standard of care focuses on avoiding skin irritants and triggers along with the use of moisturizers and topical corticosteroids (TCs). In patients with recurring severe disease, topical calcineurin inhibitors, phototherapy, and systemic agents also may be utilized.14
Avoiding Irritants and Triggers
Atopic dermatitis is worsened by skin contact with physical and chemical irritants. Exacerbating factors in AD include exposure to food allergens, dust, emotional stress, detergents, fragranced soaps, textiles, and ingredients in cosmetic products. Patients should be advised to use mild detergents and fragrance-free soaps and to avoid harsh materials such as wool. However, avoidance of specific ingredients in cosmetic products is not as straightforward because manufacturers are not required to disclose certain ingredients. In general, fragrances such as balsam of Peru and cinnamaldehyde, as well as preservatives such as parabens, isothiazolinones, and formaldehyde, should be avoided when selecting cosmetic products. Patients with AD should purchase fragrance-free products that are specifically formulated for sensitive skin. Additionally, patients should not apply makeup if their skin is irritated or oozing, as the flare may worsen.15
Moisturizers
Due to the impaired skin barrier function in patients with AD, regular application of fragrance-free moisturizers is essential to maintain hydration and to reduce xerosis. Various classes of moisturizers may be prescribed (eg, lotions, creams, gels, ointments) based on disease severity and patient preference. Light preparations such as lotions, creams, and gels have a high water content and generally are more appealing from a cosmetic standpoint because they do not create any residue on the skin. However, these options may require more frequent application because they are absorbed quickly. Heavy preparations such as ointments have longer-lasting effects due to their high oil content but tend to be less cosmetically appealing because of their greasiness.16
Although the amount and frequency of application of moisturizers has not been defined, liberal application several times daily is generally advised to minimize xerosis.17 Most physicians recommend applying moisturizer to the skin immediately after bathing to seal in moisture. Some patients prefer to use lotions and creams during the day because these products make the skin feel smooth and reserve the greasier ointments for nighttime application.
Topical Corticosteroids
Prescribed in conjunction with moisturizers, TCs are the mainstay of anti-inflammatory therapy in AD. Topical corticosteroids are classified into 7 groups based on potency, ranging from superpotent (class 1) to least potent (class 7). For acute AD flares, TCs should be applied daily for up to several weeks. Once the inflammation has resolved, it is recommended to apply TCs once to twice weekly to reduce the rate of relapse.18 Despite their effectiveness in the treatment of acute AD flares, TCs have a considerable side-effect profile. Potential adverse effects include skin atrophy, striae, telangiectasia, hypopigmentation, increased hair growth, steroid acne, growth retardation, and Cushing syndrome. Skin atrophy, which is the most common complication associated with TCs, results in shiny transparent skin, allowing for visualization of veins.19,20 Although many of these side effects will resolve after discontinuing the TCs, they are aesthetically displeasing during treatment, making it crucial for physicians to educate their patients on the proper usage of TCs to prevent negative outcomes.
Topical Calcineurin Inhibitors
Topical calcineurin inhibitors (TCIs) are a class of anti-inflammatories that are used to overcome the adverse effects of TCs. They are approved as alternatives to TCs in patients who have failed to respond to other topical treatments as well as those who have developed cutaneous atrophy from the use of TCs or have AD in sensitive areas such as the face, neck, and/or skin folds. Unlike TCs, TCIs do not cause atrophy, striae, or discoloration of the skin, which makes them more desirable from a cosmetic perspective. Their mechanism of action is distinct from TCs in that they inhibit calcineurin-dependent T-cell activation, thus preventing the transcription of inflammatory cytokines.21 Two TCIs are currently available: tacrolimus ointment 0.03% and 0.1% concentrations for moderate to severe AD and pimecrolimus cream 1% for mild to moderate AD.22 Twice-daily application of TCIs is recommended to decrease inflammation and pruritus associated with AD. Studies also have shown that intermittent use of TCIs 3 times weekly can aid in reducing relapses.23-25
The results from clinical trials demonstrate the rapid and continuous effects of both pimecrolimus and tacrolimus. In a controlled long-term study of adults, pimecrolimus provided significant relief of pruritus as soon as day 3 (P<.001).26,27 Pimecrolimus also provides long-term relief by preventing disease progression to flares, which was exemplified in a study (N=713) with no flares in 51% of pimecrolimus patients at 12 months versus 28% in the conventional treatment group (P<.001).28 Similarly, long-term studies of tacrolimus demonstrated an improvement of all symptoms of AD after 1 week of treatment. Maximal improvement was achieved with continued use of tacrolimus, and up to 1 year of tacrolimus use was found to be safe and effective.29,30 Thus, TCIs have been proven to be an effective choice in maintenance therapy for AD and have a good safety profile. The most common adverse effects of TCIs are local skin reactions, such as stinging and burning at the site of application. Rare cases of skin cancer and lymphoma have been reported; however, a causal relationship has yet to be established.31,32
Additional Therapies
Wet wrap therapy is effective for rapid control of flares and in controlling recalcitrant AD. Wet wraps function via several mechanisms; they provide a mechanical barrier against scratching, increase moisture and soften the skin, and enhance absorption of topical medications.33,34 The following method is employed when using wet wraps: an emollient or TC is applied to the area, a tubular bandage soaked in warm water is wrapped over the area, and dry bandages are used to form the outermost layer. Although wet wrap therapy is beneficial in treating AD, it is labor intensive and may require the expertise of a nurse. Thus, unlike other therapies, which patients can easily apply without interfering with their day, wet wraps must be applied at home or in a hospital setting.
Light therapy is another effective method of controlling AD. Although multiple forms of UV phototherapy are beneficial for symptom control in AD, there is no definitive recommendation regarding the specific type of light therapy due to a lack of comparative studies. Natural sunlight, narrowband UVB, broadband UVB, UVA, oral or topical psoralen plus UVA, as well as UVA and UVB can all be utilized in the treatment of AD. However, similar to natural sunlight, artificial light therapy can cause burning, blistering, hyperpigmentation, dark spots, and wrinkles. Because society places a large emphasis on maintaining a youthful appearance, patients may be hesitant to use a treatment that could potentially advance the skin’s aging process. Thus, it is important that this therapy is properly controlled to prevent further skin damage.35-37
When optimal topical regimens and phototherapy have failed to control AD, systemic immunomodulation therapies may be used. Currently, the most commonly used medications are cyclosporine 150 to 300 mg daily, methotrexate 7.5 to 25 mg weekly, mycophenolate mofetil 0.5 to 3 g daily, and azathioprine 1 to 3 mg/kg daily.38,39 Decisions regarding the specific class of drugs should be based on the patient’s AD status, comorbidities, and personal preference.
Conclusion
Atopic dermatitis is a common chronic condition that can occur at any age and cause substantial physical, psychological, social, and/or emotional stress for patients and their families. Although TCs have been the standard of treatment for many years, ongoing concerns regarding their safety have led to the use of TCIs, which overcome some of the drawbacks of steroid therapy. Phototherapy and systemic immunosuppressant therapy are reserved for patients who have not responded to optimal topical therapies. Although several therapeutic avenues exist for patients, there is a need for the development of more effective and safer drugs. Furthermore, cosmetic products created specifically for patients with AD would be beneficial, as patients often struggle to select products that do not cause more harm than good. Given the complexity of the pathogenesis of AD, further research must focus on defining the specific pathways involved in the disease and targeting these pathways with therapies.
Atopic dermatitis (AD), more commonly referred to as eczema, is a chronic pruritic inflammatory skin disease that frequently affects both children and adults. Atopic dermatitis is most common in urban and developed countries, with a prevalence of approximately 11% in the United States.1 The pathophysiology of AD is complex and not fully understood, despite the increasing incidence of the disease.2 A myriad of factors, including genetics, defects in the innate and adaptive immune response, and skin barrier abnormalities all contribute to the pathogenesis.3,4 As a result of these abnormalities, patients with AD are more prone to damage from environmental irritants and allergens.
The diagnosis of AD is made clinically based on patient history and visual assessment of the skin.5 Atopic dermatitis follows a chronic and relapsing course characterized by severe pruritus and visible skin changes including xerosis, redness, blistering, oozing, crusting, scaling, thickening, and color change.6,7 Due to the genetic predisposition to make IgE antibodies in response to common environmental and food antigens, patients also may develop allergic rhinitis, asthma, and food-induced anaphylaxis.8,9 Patients also are susceptible to cutaneous viral, fungal, and bacterial infections, the most common of which is an infection with Staphylococcus aureus.10
Atopic dermatitis can have a substantial impact on quality of life, which has been revealed in studies linking chronic skin conditions to depression, impairment of self-esteem, and financial hardship.11 Because skin appearance impacts how a person is initially perceived by others, patients often report feeling self-conscious about their disease and experience teasing or bullying.12 To improve their physical appearance, patients may incur considerable medical expenses. According to 2 population-based studies comprising more than 60,000 adults aged 18 to 85 years, individuals with AD face substantial financial burdens and utilize the health care system more than those without the disease. On average, patients with AD spend $371 to $489 per year on costly out-of-pocket medical expenses and report more absences from work.13
Although there currently is no cure for AD, treatment is aimed at relieving its symptoms and preventing acute exacerbations as well as improving cosmetic appearance to enhance quality of life. Treatment must follow a stepwise approach, which focuses on hydrating the skin, repairing the dysfunctional epithelial barrier, and controlling inflammation. Thus, the standard of care focuses on avoiding skin irritants and triggers along with the use of moisturizers and topical corticosteroids (TCs). In patients with recurring severe disease, topical calcineurin inhibitors, phototherapy, and systemic agents also may be utilized.14
Avoiding Irritants and Triggers
Atopic dermatitis is worsened by skin contact with physical and chemical irritants. Exacerbating factors in AD include exposure to food allergens, dust, emotional stress, detergents, fragranced soaps, textiles, and ingredients in cosmetic products. Patients should be advised to use mild detergents and fragrance-free soaps and to avoid harsh materials such as wool. However, avoidance of specific ingredients in cosmetic products is not as straightforward because manufacturers are not required to disclose certain ingredients. In general, fragrances such as balsam of Peru and cinnamaldehyde, as well as preservatives such as parabens, isothiazolinones, and formaldehyde, should be avoided when selecting cosmetic products. Patients with AD should purchase fragrance-free products that are specifically formulated for sensitive skin. Additionally, patients should not apply makeup if their skin is irritated or oozing, as the flare may worsen.15
Moisturizers
Due to the impaired skin barrier function in patients with AD, regular application of fragrance-free moisturizers is essential to maintain hydration and to reduce xerosis. Various classes of moisturizers may be prescribed (eg, lotions, creams, gels, ointments) based on disease severity and patient preference. Light preparations such as lotions, creams, and gels have a high water content and generally are more appealing from a cosmetic standpoint because they do not create any residue on the skin. However, these options may require more frequent application because they are absorbed quickly. Heavy preparations such as ointments have longer-lasting effects due to their high oil content but tend to be less cosmetically appealing because of their greasiness.16
Although the amount and frequency of application of moisturizers has not been defined, liberal application several times daily is generally advised to minimize xerosis.17 Most physicians recommend applying moisturizer to the skin immediately after bathing to seal in moisture. Some patients prefer to use lotions and creams during the day because these products make the skin feel smooth and reserve the greasier ointments for nighttime application.
Topical Corticosteroids
Prescribed in conjunction with moisturizers, TCs are the mainstay of anti-inflammatory therapy in AD. Topical corticosteroids are classified into 7 groups based on potency, ranging from superpotent (class 1) to least potent (class 7). For acute AD flares, TCs should be applied daily for up to several weeks. Once the inflammation has resolved, it is recommended to apply TCs once to twice weekly to reduce the rate of relapse.18 Despite their effectiveness in the treatment of acute AD flares, TCs have a considerable side-effect profile. Potential adverse effects include skin atrophy, striae, telangiectasia, hypopigmentation, increased hair growth, steroid acne, growth retardation, and Cushing syndrome. Skin atrophy, which is the most common complication associated with TCs, results in shiny transparent skin, allowing for visualization of veins.19,20 Although many of these side effects will resolve after discontinuing the TCs, they are aesthetically displeasing during treatment, making it crucial for physicians to educate their patients on the proper usage of TCs to prevent negative outcomes.
Topical Calcineurin Inhibitors
Topical calcineurin inhibitors (TCIs) are a class of anti-inflammatories that are used to overcome the adverse effects of TCs. They are approved as alternatives to TCs in patients who have failed to respond to other topical treatments as well as those who have developed cutaneous atrophy from the use of TCs or have AD in sensitive areas such as the face, neck, and/or skin folds. Unlike TCs, TCIs do not cause atrophy, striae, or discoloration of the skin, which makes them more desirable from a cosmetic perspective. Their mechanism of action is distinct from TCs in that they inhibit calcineurin-dependent T-cell activation, thus preventing the transcription of inflammatory cytokines.21 Two TCIs are currently available: tacrolimus ointment 0.03% and 0.1% concentrations for moderate to severe AD and pimecrolimus cream 1% for mild to moderate AD.22 Twice-daily application of TCIs is recommended to decrease inflammation and pruritus associated with AD. Studies also have shown that intermittent use of TCIs 3 times weekly can aid in reducing relapses.23-25
The results from clinical trials demonstrate the rapid and continuous effects of both pimecrolimus and tacrolimus. In a controlled long-term study of adults, pimecrolimus provided significant relief of pruritus as soon as day 3 (P<.001).26,27 Pimecrolimus also provides long-term relief by preventing disease progression to flares, which was exemplified in a study (N=713) with no flares in 51% of pimecrolimus patients at 12 months versus 28% in the conventional treatment group (P<.001).28 Similarly, long-term studies of tacrolimus demonstrated an improvement of all symptoms of AD after 1 week of treatment. Maximal improvement was achieved with continued use of tacrolimus, and up to 1 year of tacrolimus use was found to be safe and effective.29,30 Thus, TCIs have been proven to be an effective choice in maintenance therapy for AD and have a good safety profile. The most common adverse effects of TCIs are local skin reactions, such as stinging and burning at the site of application. Rare cases of skin cancer and lymphoma have been reported; however, a causal relationship has yet to be established.31,32
Additional Therapies
Wet wrap therapy is effective for rapid control of flares and in controlling recalcitrant AD. Wet wraps function via several mechanisms; they provide a mechanical barrier against scratching, increase moisture and soften the skin, and enhance absorption of topical medications.33,34 The following method is employed when using wet wraps: an emollient or TC is applied to the area, a tubular bandage soaked in warm water is wrapped over the area, and dry bandages are used to form the outermost layer. Although wet wrap therapy is beneficial in treating AD, it is labor intensive and may require the expertise of a nurse. Thus, unlike other therapies, which patients can easily apply without interfering with their day, wet wraps must be applied at home or in a hospital setting.
Light therapy is another effective method of controlling AD. Although multiple forms of UV phototherapy are beneficial for symptom control in AD, there is no definitive recommendation regarding the specific type of light therapy due to a lack of comparative studies. Natural sunlight, narrowband UVB, broadband UVB, UVA, oral or topical psoralen plus UVA, as well as UVA and UVB can all be utilized in the treatment of AD. However, similar to natural sunlight, artificial light therapy can cause burning, blistering, hyperpigmentation, dark spots, and wrinkles. Because society places a large emphasis on maintaining a youthful appearance, patients may be hesitant to use a treatment that could potentially advance the skin’s aging process. Thus, it is important that this therapy is properly controlled to prevent further skin damage.35-37
When optimal topical regimens and phototherapy have failed to control AD, systemic immunomodulation therapies may be used. Currently, the most commonly used medications are cyclosporine 150 to 300 mg daily, methotrexate 7.5 to 25 mg weekly, mycophenolate mofetil 0.5 to 3 g daily, and azathioprine 1 to 3 mg/kg daily.38,39 Decisions regarding the specific class of drugs should be based on the patient’s AD status, comorbidities, and personal preference.
Conclusion
Atopic dermatitis is a common chronic condition that can occur at any age and cause substantial physical, psychological, social, and/or emotional stress for patients and their families. Although TCs have been the standard of treatment for many years, ongoing concerns regarding their safety have led to the use of TCIs, which overcome some of the drawbacks of steroid therapy. Phototherapy and systemic immunosuppressant therapy are reserved for patients who have not responded to optimal topical therapies. Although several therapeutic avenues exist for patients, there is a need for the development of more effective and safer drugs. Furthermore, cosmetic products created specifically for patients with AD would be beneficial, as patients often struggle to select products that do not cause more harm than good. Given the complexity of the pathogenesis of AD, further research must focus on defining the specific pathways involved in the disease and targeting these pathways with therapies.
1. Shaw TE, Currie GP, Koudelka CW, et al. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131:67-73.
2. Deckers IA, McLean S, Linssen S, et al. Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS One. 2012;7:e39803.
3. Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242:233-246.
4. Peate I. Eczema: causes, symptoms and treatment in the community. Br J Community Nurs. 2011;16:324, 326-331.
5. Williams HC, Burney PG, Pembroke AC, et al. The U.K. Working Party’s diagnostic criteria for atopic dermatitis. III. independent hospital validation. Br J Dermatol. 1994;131:406-416.
6. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
7. Beattie P, Lewis-Jones M. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155:145-151.
8. Spergel JM. From atopic dermatitis to asthma: the atopic march [published online January 22, 2010]. Ann Allergy Asthma Immunol. 2010;105:99-106; quiz 107-109, 117.
9. Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013;62:151-161.
10. Balma-Mena A, Lara-Corrales I, Zeller J, et al. Colonization with community-acquired methicillin-resistant Staphylococcus aureus in children with atopic dermatitis: a cross-sectional study. Int J Dermatol. 2011;50:682-688.
11. Strawser MS, Storch EA, Roberti JW. The Teasing Questionnaire-Revised: measurement of childhood teasing in adults. J Anxiety Disord. 2005;19:780-792.
12. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
13. Silverberg J. Health care utilization, patient costs, and access to care in US adults with eczema: a population-based study. JAMA Dermatol. 2015;151:743-752.
14. Ellis C, Luger T, Abeck D, et al. International Consensus Conference on Atopic Dermatitis II (ICCAD II): clinical update and current treatment strategies. Br J Dermatol. 2003;148(suppl 63):3-10.
15. Kim K. Influences of environmental chemicals on atopic dermatitis. Toxicol Res. 2015;31:89-96.
16. Ridd M, Redmond N, Hollinghurst S, et al. Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial. Trials. 2015;16:304.
17. Hon KL, Ching GK, Leung TF, et al. Estimating emollient usage in patients with eczema. Clin Exp Dermatol. 2010;35:22-26.
18. Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002;147:528-537.
19. Hill CJ, Rostenberg A Jr. Adverse effects from topical steroids. Cutis. 1978;21:624-628.
20. Ruiz-Maldonado R, Zapata G, Lourdes T, et al. Cushing’s syndrome after topical application of corticosteroids. Am J Dis Child. 1982;136:274-275.
21. Grassberger M, Baumruker T, Enz A, et al. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999;141:264-273.
22. Eichenfield L, Wynnis T, Berger T. Guidelines of care for the management of atopic dermatitis: management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116-132.
23. Reitamo S, Harper J, Bos JD, et al. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol. 2004;150:554-562.
24. Ruer-Mulard M, Aberer W, Gunstone A, et al. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2009;26:551-558.
25. Breneman D, Fleischer AB Jr, Abramovits W, et al. Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol. 2008;58:990-999.
26. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream 1% (Elidel) provides significant and rapid relief of pruritus and improves disease control and quality of life in atopic dermatitis in adults. J Invest Dermatol. 2002;119:350.
27. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Dermatology. 2002;205:271-277.
28. Wahn U, Bos JD, Goodfield M, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics. 2002;110(1, pt 1):e2.
29. Kang S, Lucky AW, Pariser D, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol. 2001;44(suppl 1):S58-S64.
30. Reitamo S, Wollenberg A, Schöpf E, et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. the European Tacrolimus Ointment Study Group. Arch Dermatol. 2000;136:999-1006.
31. Frankel HC, Qureshi AA. Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis. Am J Clin Dermatol. 2012;13:113-123.
32. Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol. 2011;165:465-473.
33. Dabade TS, Davis DM, Wetter DA, et al. Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic. J Am Acad Dermatol. 2012;67:100-106.
34. Devillers AC, Oranje AP. Efficacy and safety of ‘wet-wrap’ dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature. Br J Dermatol. 2006;154:579-585.
35. Meduri NB, Vandergriff T, Rasmussen H, et al. Phototherapy in the management of atopic dermatitis: a systematic review. Photodermatol Photoimmunol Photomed. 2007;23:106-112.
36. Clayton TH, Clark SM, Turner D, et al. The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapy. Clin Exp Dermatol. 2007;32:28-33.
37. Jekler J, Larko O. UVB phototherapy of atopic dermatitis. Br J Dermatol. 1988;119:697-705.
38. Roekevisch E, Spuls PI, Kuester D, et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133:429-438.39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
1. Shaw TE, Currie GP, Koudelka CW, et al. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131:67-73.
2. Deckers IA, McLean S, Linssen S, et al. Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS One. 2012;7:e39803.
3. Boguniewicz M, Leung DY. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242:233-246.
4. Peate I. Eczema: causes, symptoms and treatment in the community. Br J Community Nurs. 2011;16:324, 326-331.
5. Williams HC, Burney PG, Pembroke AC, et al. The U.K. Working Party’s diagnostic criteria for atopic dermatitis. III. independent hospital validation. Br J Dermatol. 1994;131:406-416.
6. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
7. Beattie P, Lewis-Jones M. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155:145-151.
8. Spergel JM. From atopic dermatitis to asthma: the atopic march [published online January 22, 2010]. Ann Allergy Asthma Immunol. 2010;105:99-106; quiz 107-109, 117.
9. Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013;62:151-161.
10. Balma-Mena A, Lara-Corrales I, Zeller J, et al. Colonization with community-acquired methicillin-resistant Staphylococcus aureus in children with atopic dermatitis: a cross-sectional study. Int J Dermatol. 2011;50:682-688.
11. Strawser MS, Storch EA, Roberti JW. The Teasing Questionnaire-Revised: measurement of childhood teasing in adults. J Anxiety Disord. 2005;19:780-792.
12. Magin P, Adams J, Heading G, et al. Experiences of appearance-related teasing and bullying in skin diseases and their psychological sequelae: results of a qualitative study. Scand J Caring Sci. 2008;22:430-436.
13. Silverberg J. Health care utilization, patient costs, and access to care in US adults with eczema: a population-based study. JAMA Dermatol. 2015;151:743-752.
14. Ellis C, Luger T, Abeck D, et al. International Consensus Conference on Atopic Dermatitis II (ICCAD II): clinical update and current treatment strategies. Br J Dermatol. 2003;148(suppl 63):3-10.
15. Kim K. Influences of environmental chemicals on atopic dermatitis. Toxicol Res. 2015;31:89-96.
16. Ridd M, Redmond N, Hollinghurst S, et al. Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial. Trials. 2015;16:304.
17. Hon KL, Ching GK, Leung TF, et al. Estimating emollient usage in patients with eczema. Clin Exp Dermatol. 2010;35:22-26.
18. Hanifin J, Gupta AK, Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients. Br J Dermatol. 2002;147:528-537.
19. Hill CJ, Rostenberg A Jr. Adverse effects from topical steroids. Cutis. 1978;21:624-628.
20. Ruiz-Maldonado R, Zapata G, Lourdes T, et al. Cushing’s syndrome after topical application of corticosteroids. Am J Dis Child. 1982;136:274-275.
21. Grassberger M, Baumruker T, Enz A, et al. A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999;141:264-273.
22. Eichenfield L, Wynnis T, Berger T. Guidelines of care for the management of atopic dermatitis: management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116-132.
23. Reitamo S, Harper J, Bos JD, et al. 0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial. Br J Dermatol. 2004;150:554-562.
24. Ruer-Mulard M, Aberer W, Gunstone A, et al. Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2009;26:551-558.
25. Breneman D, Fleischer AB Jr, Abramovits W, et al. Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. J Am Acad Dermatol. 2008;58:990-999.
26. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream 1% (Elidel) provides significant and rapid relief of pruritus and improves disease control and quality of life in atopic dermatitis in adults. J Invest Dermatol. 2002;119:350.
27. Meurer M, Fölster-Holst R, Wozel G, et al. Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study. Dermatology. 2002;205:271-277.
28. Wahn U, Bos JD, Goodfield M, et al. Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children. Pediatrics. 2002;110(1, pt 1):e2.
29. Kang S, Lucky AW, Pariser D, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol. 2001;44(suppl 1):S58-S64.
30. Reitamo S, Wollenberg A, Schöpf E, et al. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. the European Tacrolimus Ointment Study Group. Arch Dermatol. 2000;136:999-1006.
31. Frankel HC, Qureshi AA. Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis. Am J Clin Dermatol. 2012;13:113-123.
32. Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol. 2011;165:465-473.
33. Dabade TS, Davis DM, Wetter DA, et al. Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic. J Am Acad Dermatol. 2012;67:100-106.
34. Devillers AC, Oranje AP. Efficacy and safety of ‘wet-wrap’ dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature. Br J Dermatol. 2006;154:579-585.
35. Meduri NB, Vandergriff T, Rasmussen H, et al. Phototherapy in the management of atopic dermatitis: a systematic review. Photodermatol Photoimmunol Photomed. 2007;23:106-112.
36. Clayton TH, Clark SM, Turner D, et al. The treatment of severe atopic dermatitis in childhood with narrowband ultraviolet B phototherapy. Clin Exp Dermatol. 2007;32:28-33.
37. Jekler J, Larko O. UVB phototherapy of atopic dermatitis. Br J Dermatol. 1988;119:697-705.
38. Roekevisch E, Spuls PI, Kuester D, et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133:429-438.39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
39. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4:1-191.
Practice Points
- Cosmetic symptoms of atopic dermatitis can have a serious impact on the patient’s quality of life.
- Avoidance of flares and prevention of triggers is an important aspect of care.
- Treatment options range from optimized skin care to topical prescription therapies to systemic medications.
VIDEO: What’s new on atopic dermatitis drugs and cancer concerns?
WAIKOLOA, HAWAII – Topical calcineurin inhibitors’ boxed warnings give many patients and physicians pause over cancer concerns – but a new database analysis may put some minds at ease about the drugs’ use for atopic dermatitis.
“Pimecrolimus and tacrolimus are given topically, not internally – very little absorption occurs. So, it was hoped that ... we wouldn’t see cancer increases in these patients,” explained Dr. Joseph F. Fowler Jr., clinical professor of dermatology at the University of Louisville (Ky.). “And in fact, that’s exactly what was shown in this large study.”
In an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Fowler discussed the data from new research examining cancer incidence and calcineurin inhibitor use.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAIKOLOA, HAWAII – Topical calcineurin inhibitors’ boxed warnings give many patients and physicians pause over cancer concerns – but a new database analysis may put some minds at ease about the drugs’ use for atopic dermatitis.
“Pimecrolimus and tacrolimus are given topically, not internally – very little absorption occurs. So, it was hoped that ... we wouldn’t see cancer increases in these patients,” explained Dr. Joseph F. Fowler Jr., clinical professor of dermatology at the University of Louisville (Ky.). “And in fact, that’s exactly what was shown in this large study.”
In an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Fowler discussed the data from new research examining cancer incidence and calcineurin inhibitor use.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WAIKOLOA, HAWAII – Topical calcineurin inhibitors’ boxed warnings give many patients and physicians pause over cancer concerns – but a new database analysis may put some minds at ease about the drugs’ use for atopic dermatitis.
“Pimecrolimus and tacrolimus are given topically, not internally – very little absorption occurs. So, it was hoped that ... we wouldn’t see cancer increases in these patients,” explained Dr. Joseph F. Fowler Jr., clinical professor of dermatology at the University of Louisville (Ky.). “And in fact, that’s exactly what was shown in this large study.”
In an interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Fowler discussed the data from new research examining cancer incidence and calcineurin inhibitor use.
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SDEF HAWAII DERMATOLOGY SEMINAR
SDEF: Have higher degree of suspicion for pediatric allergic contact dermatitis
Allergic contact dermatitis is often missed in pediatric patients who present with eczema-like skin eruptions, in part because less is known about ACD in children than in adults.
“Often when we see a child with dermatitis, we automatically think of atopic dermatitis, but we should also consider the possibility of allergic contact dermatitis,” Dr. Joseph F. Fowler Jr. said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
A 2012 cohort study of 349 children between 0 and 15 years indicated that even very young children who were patch tested for common allergens had at least one positive result. Investigators found that nearly three-quarters of children studied tested positive for at least one allergen, typically nickel, other metals, fragrance, or preservatives (Dermatitis. 2012 Nov-Dec;23[6]:275-80).
“This is very similar to what we see in the adult population,” said Dr. Fowler, clinical professor of dermatology at the University of Louisville (Ky.). “Other studies in recent years have borne this out.”
Dr. Fowler suggested having a high degree of suspicion for ACD, especially when pediatric patients present with:
• Chronic, difficult to control atopic condition, as this could indicate a systemic reaction.
• Localized or facial dermatitis, as this could indicate the point of contact with an allergen.
• Scattered, generalized dermatitis, which also could represent systemic allergic contact dermatitis.
• Dermatitis that worsens, despite otherwise adequate treatment regimen.
• Reactions following contact with metals, fragrances, topical components, such as preservatives or neomycin.
“In these situations, patch testing will help determine that an allergen is implicated,” Dr. Fowler said.
In children with eczema, Dr. Fowler recommended patch testing when the eczema is not in the typical areas such as behind the knees or elbows, or if it started in typical areas and then spread elsewhere, especially in children around 5 years old.
“The moral of the story is that kids can be allergic to the same things as adults, even though we have less about this in the literature,” Dr. Fowler. “Skin testing or blood testing for food allergies, unless very strongly positive, usually aren’t helpful in the management of the atopic individual. Patch test more and prick test less.”
Dr. Fowler disclosed a number of relationships with companies in the dermatology space. SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
Allergic contact dermatitis is often missed in pediatric patients who present with eczema-like skin eruptions, in part because less is known about ACD in children than in adults.
“Often when we see a child with dermatitis, we automatically think of atopic dermatitis, but we should also consider the possibility of allergic contact dermatitis,” Dr. Joseph F. Fowler Jr. said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
A 2012 cohort study of 349 children between 0 and 15 years indicated that even very young children who were patch tested for common allergens had at least one positive result. Investigators found that nearly three-quarters of children studied tested positive for at least one allergen, typically nickel, other metals, fragrance, or preservatives (Dermatitis. 2012 Nov-Dec;23[6]:275-80).
“This is very similar to what we see in the adult population,” said Dr. Fowler, clinical professor of dermatology at the University of Louisville (Ky.). “Other studies in recent years have borne this out.”
Dr. Fowler suggested having a high degree of suspicion for ACD, especially when pediatric patients present with:
• Chronic, difficult to control atopic condition, as this could indicate a systemic reaction.
• Localized or facial dermatitis, as this could indicate the point of contact with an allergen.
• Scattered, generalized dermatitis, which also could represent systemic allergic contact dermatitis.
• Dermatitis that worsens, despite otherwise adequate treatment regimen.
• Reactions following contact with metals, fragrances, topical components, such as preservatives or neomycin.
“In these situations, patch testing will help determine that an allergen is implicated,” Dr. Fowler said.
In children with eczema, Dr. Fowler recommended patch testing when the eczema is not in the typical areas such as behind the knees or elbows, or if it started in typical areas and then spread elsewhere, especially in children around 5 years old.
“The moral of the story is that kids can be allergic to the same things as adults, even though we have less about this in the literature,” Dr. Fowler. “Skin testing or blood testing for food allergies, unless very strongly positive, usually aren’t helpful in the management of the atopic individual. Patch test more and prick test less.”
Dr. Fowler disclosed a number of relationships with companies in the dermatology space. SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
Allergic contact dermatitis is often missed in pediatric patients who present with eczema-like skin eruptions, in part because less is known about ACD in children than in adults.
“Often when we see a child with dermatitis, we automatically think of atopic dermatitis, but we should also consider the possibility of allergic contact dermatitis,” Dr. Joseph F. Fowler Jr. said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
A 2012 cohort study of 349 children between 0 and 15 years indicated that even very young children who were patch tested for common allergens had at least one positive result. Investigators found that nearly three-quarters of children studied tested positive for at least one allergen, typically nickel, other metals, fragrance, or preservatives (Dermatitis. 2012 Nov-Dec;23[6]:275-80).
“This is very similar to what we see in the adult population,” said Dr. Fowler, clinical professor of dermatology at the University of Louisville (Ky.). “Other studies in recent years have borne this out.”
Dr. Fowler suggested having a high degree of suspicion for ACD, especially when pediatric patients present with:
• Chronic, difficult to control atopic condition, as this could indicate a systemic reaction.
• Localized or facial dermatitis, as this could indicate the point of contact with an allergen.
• Scattered, generalized dermatitis, which also could represent systemic allergic contact dermatitis.
• Dermatitis that worsens, despite otherwise adequate treatment regimen.
• Reactions following contact with metals, fragrances, topical components, such as preservatives or neomycin.
“In these situations, patch testing will help determine that an allergen is implicated,” Dr. Fowler said.
In children with eczema, Dr. Fowler recommended patch testing when the eczema is not in the typical areas such as behind the knees or elbows, or if it started in typical areas and then spread elsewhere, especially in children around 5 years old.
“The moral of the story is that kids can be allergic to the same things as adults, even though we have less about this in the literature,” Dr. Fowler. “Skin testing or blood testing for food allergies, unless very strongly positive, usually aren’t helpful in the management of the atopic individual. Patch test more and prick test less.”
Dr. Fowler disclosed a number of relationships with companies in the dermatology space. SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Mechanism for dust mite–triggered atopic dermatitis identified
Researchers have identified a possible mechanism by which house dust mites could trigger the development of atopic dermatitis in individuals with a genetic predisposition.
The study, published online Feb. 10 in Science Translational Medicine, took skin and blood samples from individuals with atopic dermatitis and healthy controls, then exposed the samples to house dust mite allergen.
They found that in individuals with atopic dermatitis, this exposure modified phospholipids in the skin to release lipid antigens that then drove T-cell reactivity and inflammation (Sci Transl Med. 2016 Feb 10. doi: 10.1126/scitranslmed.aad6833).
Furthermore, the study suggested that the skin barrier protein filaggrin can inhibit the modified phospholipid activity and decrease the skin inflammation caused by allergen exposure in atopic dermatitis; however, individuals with atopic dermatitis are more likely to have defective filaggrin.
“The data would support therapeutic approaches to inhibit allergen-derived PLA2 [phospholipase A2] activity, together with treatments that target the downstream immunological effector pathways,” wrote Dr. Rachael Jarrett of the University of Oxford (England) and coauthors.
The study was funded by the U.K. Medical Research Council and National Institute for Health Research Biomedical Research Centre, the National Institutes of Health, and the Burroughs Wellcome Fund in Translational Medicine. Several of the researchers acknowledged grants and pharmaceutical company support. No conflicts of interest were declared.
Researchers have identified a possible mechanism by which house dust mites could trigger the development of atopic dermatitis in individuals with a genetic predisposition.
The study, published online Feb. 10 in Science Translational Medicine, took skin and blood samples from individuals with atopic dermatitis and healthy controls, then exposed the samples to house dust mite allergen.
They found that in individuals with atopic dermatitis, this exposure modified phospholipids in the skin to release lipid antigens that then drove T-cell reactivity and inflammation (Sci Transl Med. 2016 Feb 10. doi: 10.1126/scitranslmed.aad6833).
Furthermore, the study suggested that the skin barrier protein filaggrin can inhibit the modified phospholipid activity and decrease the skin inflammation caused by allergen exposure in atopic dermatitis; however, individuals with atopic dermatitis are more likely to have defective filaggrin.
“The data would support therapeutic approaches to inhibit allergen-derived PLA2 [phospholipase A2] activity, together with treatments that target the downstream immunological effector pathways,” wrote Dr. Rachael Jarrett of the University of Oxford (England) and coauthors.
The study was funded by the U.K. Medical Research Council and National Institute for Health Research Biomedical Research Centre, the National Institutes of Health, and the Burroughs Wellcome Fund in Translational Medicine. Several of the researchers acknowledged grants and pharmaceutical company support. No conflicts of interest were declared.
Researchers have identified a possible mechanism by which house dust mites could trigger the development of atopic dermatitis in individuals with a genetic predisposition.
The study, published online Feb. 10 in Science Translational Medicine, took skin and blood samples from individuals with atopic dermatitis and healthy controls, then exposed the samples to house dust mite allergen.
They found that in individuals with atopic dermatitis, this exposure modified phospholipids in the skin to release lipid antigens that then drove T-cell reactivity and inflammation (Sci Transl Med. 2016 Feb 10. doi: 10.1126/scitranslmed.aad6833).
Furthermore, the study suggested that the skin barrier protein filaggrin can inhibit the modified phospholipid activity and decrease the skin inflammation caused by allergen exposure in atopic dermatitis; however, individuals with atopic dermatitis are more likely to have defective filaggrin.
“The data would support therapeutic approaches to inhibit allergen-derived PLA2 [phospholipase A2] activity, together with treatments that target the downstream immunological effector pathways,” wrote Dr. Rachael Jarrett of the University of Oxford (England) and coauthors.
The study was funded by the U.K. Medical Research Council and National Institute for Health Research Biomedical Research Centre, the National Institutes of Health, and the Burroughs Wellcome Fund in Translational Medicine. Several of the researchers acknowledged grants and pharmaceutical company support. No conflicts of interest were declared.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: Dust mite allergen modifies skin phospholipids and triggers inflammation in atopic dermatitis.
Major finding: Individuals with atopic dermatitis have a defective skin protein that increases their reactivity to house dust mite allergen.
Data source: Laboratory study.
Disclosures: The study was funded by the U.K. Medical Research Council and National Institute for Health Research Biomedical Research Centre, the National Institutes of Health, and the Burroughs Wellcome Fund in Translational Medicine. Several of the researchers acknowledged grants and pharmaceutical company support. No conflicts of interest were declared.
Average person with atopic dermatitis has no increased risk of actinic keratosis or nonmelanoma skin cancer
People with atopic dermatitis do not appear to be at greater risk for actinic keratosis or basal cell and squamous cell cancer, according to a recent population-based, cross-sectional study.
“This is the first study to examine the association between atopic dermatitis and actinic keratosis [AK]. Our findings suggest that within a population-based sample, atopic dermatitis patients do not have more AKs than the rest of the population. Patients with atopic dermatitis were not found to have more AKs or keratotic cancers [basal or squamous cell cancers]. Moreover, individuals with atopic dermatitis seem to be less likely to develop multiple AKs,” said Dr. Enes Hajdarbegovic and his associates of the Erasmus Medical Centre, Rotterdam, the Netherlands.
The study is part of an ongoing, prospective, Dutch population-based cohort study that follows people in a district of Rotterdam since 1990. There are now 14,926 participants in the database. The current study included 4,375 participants who had undergone full body skin examinations; 56% of patients were female, and the mean age was 68 years (Br J Dermatol. 2016 Jan 29. doi: 10.1111/bjd.14423).
Twenty-four percent had 1 or more AKs; 57% had 1-3 of these lesions; 23% had 4-9, and 20% had more than 10. The mean age of participants with AK was significantly higher, compared with those without AK (73 years vs. 66 years; P less than .01).
Of the 4,375 participants screened, 6.3% met the diagnostic criteria for atopic dermatitis. A lower proportion of those with atopic dermatitis had AK: 16% vs. 24%, respectively (P = .002). In a multinomial model, atopic dermatitis patients were 78% less likely to have 10 or more AKs than were those without atopic dermatitis. No effect of atopic dermatitis was found on basal cell cancer (adjusted odds ratio, 0.71) and squamous cell cancer (adjusted OR, 1.54).
The authors explained that it is already known that patients with severe atopic dermatitis exposed to ultraviolet light and immunosuppressants are at increased risk of keratinocyte malignancies. This study shows that a community-dwelling person with moderate atopic dermatitis does not develop more AKs or keratinocyte cancers.
The investigators said they had no relevant financial disclosures.
People with atopic dermatitis do not appear to be at greater risk for actinic keratosis or basal cell and squamous cell cancer, according to a recent population-based, cross-sectional study.
“This is the first study to examine the association between atopic dermatitis and actinic keratosis [AK]. Our findings suggest that within a population-based sample, atopic dermatitis patients do not have more AKs than the rest of the population. Patients with atopic dermatitis were not found to have more AKs or keratotic cancers [basal or squamous cell cancers]. Moreover, individuals with atopic dermatitis seem to be less likely to develop multiple AKs,” said Dr. Enes Hajdarbegovic and his associates of the Erasmus Medical Centre, Rotterdam, the Netherlands.
The study is part of an ongoing, prospective, Dutch population-based cohort study that follows people in a district of Rotterdam since 1990. There are now 14,926 participants in the database. The current study included 4,375 participants who had undergone full body skin examinations; 56% of patients were female, and the mean age was 68 years (Br J Dermatol. 2016 Jan 29. doi: 10.1111/bjd.14423).
Twenty-four percent had 1 or more AKs; 57% had 1-3 of these lesions; 23% had 4-9, and 20% had more than 10. The mean age of participants with AK was significantly higher, compared with those without AK (73 years vs. 66 years; P less than .01).
Of the 4,375 participants screened, 6.3% met the diagnostic criteria for atopic dermatitis. A lower proportion of those with atopic dermatitis had AK: 16% vs. 24%, respectively (P = .002). In a multinomial model, atopic dermatitis patients were 78% less likely to have 10 or more AKs than were those without atopic dermatitis. No effect of atopic dermatitis was found on basal cell cancer (adjusted odds ratio, 0.71) and squamous cell cancer (adjusted OR, 1.54).
The authors explained that it is already known that patients with severe atopic dermatitis exposed to ultraviolet light and immunosuppressants are at increased risk of keratinocyte malignancies. This study shows that a community-dwelling person with moderate atopic dermatitis does not develop more AKs or keratinocyte cancers.
The investigators said they had no relevant financial disclosures.
People with atopic dermatitis do not appear to be at greater risk for actinic keratosis or basal cell and squamous cell cancer, according to a recent population-based, cross-sectional study.
“This is the first study to examine the association between atopic dermatitis and actinic keratosis [AK]. Our findings suggest that within a population-based sample, atopic dermatitis patients do not have more AKs than the rest of the population. Patients with atopic dermatitis were not found to have more AKs or keratotic cancers [basal or squamous cell cancers]. Moreover, individuals with atopic dermatitis seem to be less likely to develop multiple AKs,” said Dr. Enes Hajdarbegovic and his associates of the Erasmus Medical Centre, Rotterdam, the Netherlands.
The study is part of an ongoing, prospective, Dutch population-based cohort study that follows people in a district of Rotterdam since 1990. There are now 14,926 participants in the database. The current study included 4,375 participants who had undergone full body skin examinations; 56% of patients were female, and the mean age was 68 years (Br J Dermatol. 2016 Jan 29. doi: 10.1111/bjd.14423).
Twenty-four percent had 1 or more AKs; 57% had 1-3 of these lesions; 23% had 4-9, and 20% had more than 10. The mean age of participants with AK was significantly higher, compared with those without AK (73 years vs. 66 years; P less than .01).
Of the 4,375 participants screened, 6.3% met the diagnostic criteria for atopic dermatitis. A lower proportion of those with atopic dermatitis had AK: 16% vs. 24%, respectively (P = .002). In a multinomial model, atopic dermatitis patients were 78% less likely to have 10 or more AKs than were those without atopic dermatitis. No effect of atopic dermatitis was found on basal cell cancer (adjusted odds ratio, 0.71) and squamous cell cancer (adjusted OR, 1.54).
The authors explained that it is already known that patients with severe atopic dermatitis exposed to ultraviolet light and immunosuppressants are at increased risk of keratinocyte malignancies. This study shows that a community-dwelling person with moderate atopic dermatitis does not develop more AKs or keratinocyte cancers.
The investigators said they had no relevant financial disclosures.
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point: People with atopic dermatitis do not appear to be at greater risk for actinic keratosis or basal cell and squamous cell cancer.
Major finding: In a multinomial model, atopic dermatitis patients were 78% less likely to have 10 or more actinic keratoses than were those without atopic dermatitis. No effect of atopic dermatitis was found on basal cell cancer (adjusted OR, 0.71) and squamous cell cancer (adjusted OR, 1.54).
Data source: A prospective, Dutch population-based cohort study of 4,375 participants who had undergone full body skin examinations.
Disclosures: The investigators said they had no relevant financial disclosures.
VIDEO: Prophylaxis for atopic dermatitis
GRAND CAYMAN – What simple prophylactic measures can you recommend to parents of children at risk of atopic dermatitis? In an interview at this year’s Caribbean Dermatology Symposium, Dr. Albert C. Yan, section chief of dermatology at the Children’s Hospital of Philadelphia and professor of pediatrics and dermatology, University of Pennsylvania, Philadelphia, discusses the evidence indicating that early use of moisturizers reduces the risk of atopic dermatitis in children at risk.
The meeting is provided by Global Academy for Medical Education. Global Academy and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
GRAND CAYMAN – What simple prophylactic measures can you recommend to parents of children at risk of atopic dermatitis? In an interview at this year’s Caribbean Dermatology Symposium, Dr. Albert C. Yan, section chief of dermatology at the Children’s Hospital of Philadelphia and professor of pediatrics and dermatology, University of Pennsylvania, Philadelphia, discusses the evidence indicating that early use of moisturizers reduces the risk of atopic dermatitis in children at risk.
The meeting is provided by Global Academy for Medical Education. Global Academy and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
GRAND CAYMAN – What simple prophylactic measures can you recommend to parents of children at risk of atopic dermatitis? In an interview at this year’s Caribbean Dermatology Symposium, Dr. Albert C. Yan, section chief of dermatology at the Children’s Hospital of Philadelphia and professor of pediatrics and dermatology, University of Pennsylvania, Philadelphia, discusses the evidence indicating that early use of moisturizers reduces the risk of atopic dermatitis in children at risk.
The meeting is provided by Global Academy for Medical Education. Global Academy and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
AT THE CARIBBEAN DERMATOLOGY SYMPOSIUM
