Clinical Review & Education
Review
Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management Girish C. Mohan, BS; Peter A. Lio, MD
IMPORTANCE Atopic dermatitis (AD) is a common skin condition treated by dermatologists,
allergists, pediatricians, and primary care physicians. Several treatment guidelines and therapeutic parameters exist for the management of this disease. Health care professionals may be unaware of guidelines created by specialty organizations other than their own. OBJECTIVE To review, compare, and contrast the most recent AD management guidelines. EVIDENCE REVIEW The guidelines for AD management published by the American Academy of Dermatology 2014 work group were compared with those created by the 2012 Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. International guidelines created by the 2012 European Task Force on Atopic Dermatitis and the 2013 Asia–Pacific Consensus Group for Atopic Dermatitis were also considered. FINDINGS Several differences among the guidelines suggest that there may be disparity in the perceptions of AD between US dermatologists and allergists and health care professionals in other areas of the world. There are notable differences among the guidelines regarding the recommendations for the use of diluted bleach baths, vitamin D, and environmental modifications. CONCLUSIONS AND RELEVANCE Comparison of different guidelines may ultimately augment knowledge of treatment strategies and enhance realization of biases in the understanding and management of AD. JAMA Dermatol. doi:10.1001/jamadermatol.2015.0250 Published online April 8, 2015.
A
topic dermatitis (AD) is a chronic, inflammatory skin condition commonly treated by dermatologists, allergists, pediatricians, and family practitioners. As the pathogenesis of AD is complex and multifactorial, there are many different therapies. In addition, there is evidence that subtypes of AD exist with distinct pathogeneses, consequently requiring different approaches to management. Management of AD addresses a wide variety of issues, ranging from handling acute exacerbations to modifying environmental exposures. Different groups of physicians treating AD may have different strategies and outcomes. Saavedra et al1 reported that allergists were more likely than dermatologists to prescribe elimination diets and use dietary change alone as therapy. Henderson et al2 showed that dermatologists were more likely than other physicians to use topical corticosteroids (TCS), especially high-potency agents. Even within dermatology there is some discrepancy: Japanese dermatologists were less likely to use TCS and more likely to use alternative treatments than were their colleagues in the United States or United Kingdom.3
Author Affiliations: Currently a medical student at University of Illinois College of Medicine, Chicago (Mohan); Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Lio); Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Lio). Corresponding Author: Peter A. Lio, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, 1455 N Milwaukee Ave, Second Floor, Chicago, IL 60622 ([email protected]).
Updated treatment guidelines to help direct physicians in the management of this multifaceted condition allow comparison of approaches to disease management. We review these guidelines to highlight potentially important differences among the guidelines, which could suggest variations in conceptualization of the disorder between allergists and dermatologists, and/or highlight biases regarding the subtypes of patients with AD.
Methods Published guidelines from the following organizations were reviewed: 1. The American Academy of Dermatology (AAD)4-7 2. The Joint Task Force on Practice Parameters (JTF), representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology8,9 3. The 2012 European Task Force on Atopic Dermatitis10,11
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4. The 2013 Asia–Pacific Consensus Group for Atopic Dermatitis12 Both of us reviewed the guidelines and their similarities and differences (Box and Table). Any differences were resolved by discussion. Each organization had distinct approaches to developing their respective guidelines: The AAD performed a systematic search of PubMed, the Cochrane Library, and the Global Resources for Eczema Trials databases using a number of medical subject headings (eg, atopic dermatitis, topical corticosteroid, nonpharmacologic, calcineurin inhibitor) limited to the English language, and used the strength of the recommendation taxonomy to grade the evidence. A total of 246 articles were included in the review, and evidence tables were used by the work group to develop the recommendations. Expert opinion was relied on in situations where evidence was not available. The JTF performed a systematic literature review of PubMed and the Cochrane Database using a number of medical subject headings (eg, atopic dermatitis/atopic eczema, diagnosis, management, immunomodulating agents), and a classification of recommendations and evidence was used to grade the evidence. A consensus expert opinion on each section was obtained before publication. The European Task Force on Atopic Dermatitis evaluated existing evidence-based guidelines using the Appraisal of Guidelines Research and Evaluation method. They also searched the newer literature
Box. Similarities Among Recommendations From AAD Guidelines,4-7 JTF Guidelines,8,9 European Guidelines,10,11 and Asia–Pacific Guidelines12 Regarding AD Management Similarities Among the Guidelines Topical Therapies
Emollients, topical corticosteroids, and topical calcineurin-inhibitors are mainstays of management Not enough evidence to definitively recommend specialty emollients (eg, ceramide-dominant preparations) Maintenance therapy with topical corticosteroids or topical calcineurin-inhibitors can be used to prevent flares Wet wraps or dressings with topical corticosteroids can be recommended, especially during disease flares No role for topical antihistamines Systemic Therapies
Phototherapy and oral immunomodulatory therapies are to be used for chronic AD recalcitrant to topical therapy No significant differences in efficacy among oral treatment options (cyclosporine, methotrexate, azathioprine, mycophenolate mofetil) have been clearly demonstrated Oral antihistamines are useful for sedation if sleep is disturbed; not recommended on a regular basis for itch Oral antibiotics recommended if clinically overt secondary infection is present Other Management Considerations
Educational interventions regarding managing their disease (eg, videos, written instructions) may help patients Abbreviations: AAD, American Academy of Dermatology; AD, atopic dermatitis; JTF, Joint Task Force.
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using MEDLINE, EMBASE, and the Cochrane Library. Consensus was reached using the Delphi method. An external review by all European dermatologic societies was also performed before publication. Evidence was systematically graded and classified by strength. The Asia–Pacific Consensus Group for Atopic Dermatitis represented evidence- and experience-based recommendations aimed at physicians in the Asia–Pacific region, but did not elaborate on their approach to gathering the data and did not grade the evidence explicitly in the guideline document.
Results There was disparity among the groups in terms of the approach to gathering and grading the evidence. However, all appeared to acknowledge the relatively large gaps in high-quality evidence and the necessity to use lower-quality studies and clinical experience to develop a comprehensive guideline.
Topical Therapy Topical Emollients and Anti-Inflammatory Therapy
All the management guidelines review topical therapy for AD. The guidelines agree on the basic tenets of AD management such as using emollients as first-line therapy, with inconclusive evidence that specialized moisturizers, such as ceramide-dominant preparations, are more effective than others. All the guidelines similarly recommend the use of TCS as initial anti-inflammatory therapy and the use of topical calcineurin inhibitors in specific situations, such as for eczema on the face or eyelids or for proactive maintenance therapy to prevent flares. All the guidelines also recommend wet-wrap therapy with TCS for severe manifestations of disease and find no role for topical antihistamines (Box). Several differences among the guidelines do exist, however. The AAD group discusses combination TCS and topical calcineurin inhibitor therapy being potentially more efficacious than either used alone and the European Task Force specifically recommends against combination therapy, concluding that it is not useful, while the other groups remain silent on this point (Table). The “soak and smear technique” with topical anti-inflammatories for severely inflamed lesions was endorsed by the AAD and the Asia–Pacific groups, while the JTF only mentioned applying moisturizer after soaking in water. Notably, the AAD and Asia–Pacific guidelines promote physicians counseling patients against incorrect beliefs about TCS (ie, fear of corticosteroid use) to prevent poor efficacy of treatment owing to nonadherence; this issue is not broached by the JTF or the European group. Topical Antimicrobial Therapy
The AAD group concluded that patients with moderate to severe AD with frequent bacterial infections could benefit from diluted bleach baths. The European Task Force and Asia–Pacific group also endorse the use of diluted bleach baths, while the JTF is less conclusive about this therapy, stating that bleach baths require more study and that the most appropriate AD subtype that would benefit from this treatment remains unclear (Table). The JTF articulates, however, that the use of antiseptics (eg, triclosan and chlorhexidine gluconate) may help patients with excessive Staphylococcus aureus
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Table. Differences Among Recommendations From AAD Guidelines, JTF Guidelines, European Guidelines, and Asia–Pacific Guidelines Regarding AD Management Guideline AAD4-7
JTF8,9
European10,11
Asia-Pacific12
TCS + TCI combination
Combination TCS and TCI therapy may be more effective than either alone
Not discussed
Recommend against combination TCS and TCI therapy, concluding it is not useful
Not discussed
“Soak and smear” technique
Soak and smear technique with TCS or TCI recommended
Soak and smear technique with moisturizer recommeded
Not discussed
Soak and smear technique with TCS recommended
Fear of corticosteroid use
Promotes counseling patients regarding fear of corticosteroid use
Not discussed
Not discussed
Disucsses a need to address concerns regarding fear of corticosteroid use
Bleach baths
Bleach baths effective as therapy Bleach baths are promising but require more study to decolonize Staphylococcus aureus
Bleach baths appear to be useful in reducing AD severity
Bleach baths effective in patients with AD who have secondary bacterial infection
Topical antiseptics
Topical antiseptics not supported as they provide no benefit
Topical antiseptics can be used to control S aureus colonization
Topical antiseptics may be considered but may not help
Topical antiseptics not supported as they provide no benefit
Topical tar
Not enough data to recommend topical tar use
Topical tar may be of benefit but should not be used on acutely inflamed skin
Not discussed
Not discussed
Oral medications
Tabulates recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral immunomodulatory therapies
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Antibiotics for secondary infection, with or without skin culture
Skin culture if initial antibiotic therapy fails
Suggest skin culture for methicillin-resistant S aureus before initially prescribing antibiotics
Not discussed
Not discussed
Treatment Topical Therapies
Systemic Therapies
Other Management Considerations Silver-impregnated clothing and silk clothing
Efficacy of silver-impregnated or Silver-impregnated clothing or silk clothing unclear silk clothing may help patients
Silver-impregnated clothing or Not discussed silk clothing may help patients
Bath additives
Not enough evidence to support bath additives
Bath additives (eg, oatmeal and baking soda) may have antipruritic effects
Not discussed
Emollient additives may be used while bathing
Vitamin D
Not enough evidence to recommend vitamin D use
Supports vitamin D use
Not enough evidence to recommend vitamin D use
Not discussed
Environmental modifications
Not enough evidence to support laundry modifications; temperature and humidity modifications not discussed
Recommend environmental modifications (temperature and humidity control and laundry modifications)
Avoiding irritating fabrics and occlusive clothing is recommended
Not discussed
Aeroallergens
Testing needed before aeroallergen minimization indicated; supports only house dust mite covers
Supports minimizing exposure to aeroallergens without testing and use of house dust mite covers, weekly bedding washes, and removing carpeting
Supports minimizing exposure to house dust mites without testing
Not discussed
Allergen-specific immunotherapy
Not enough evidence to support immunotherapy
Testing needed before using immunotherapy to specific allergens
Testing needed before using immunotherapy to specific allergens
Not discussed
Food allergy testing
Supports diagnostic elimination diet for 4-6 weeks or controlled oral food challenge if specific food allergy suspected clinically
Recommends food-specific IgE testing if specific food allergy suspected clinically; oral food challenge only if IgE test results are negative
Recommends controlled oral food challenge if specific food allergy suspected clinically
Not discussed
Psychological care
Not discussed
Recommends psychological evaluation and treatment for patients with emotional distress if it is affecting treatment adherence
Psychosomatic counseling can be helpful for patients
Not discussed
Abbreviations: AAD, American Academy of Dermatology; AD, atopic dermatitis; JTF, Joint Task Force; TCI, topical calcineurin-inhibitors; TCS, topical corticosteroids.
colonization, in agreement with the European guidelines that also place antiseptics in their recommendations. The AAD directly opposes this recommendation by stating they did not find any clear benefit for topical antibiotics/antiseptics, in accord with the Asia– Pacific group.
Other Topical Therapies
Other differences in topical therapy recommendations include the JTF and Asia–Pacific groups suggesting that additives in bathwater (eg, oatmeal and emollients) may have beneficial effects. On the other hand, the AAD group does not promote the use of bath addi-
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tives because they found no convincing supportive evidence of their effectiveness, while the European guidelines do not discuss them at all.
Oral and Systemic Therapy The guidelines also provide recommendations on oral and systemic therapies for AD (Table). All agree that oral and systemic therapies are to be used for chronic AD recalcitrant to proper skin care and topical therapies. All the guidelines discuss many of the same therapies that may be used (eg, phototherapy, cyclosporine, methotrexate, azathioprine, and systemic corticosteroids) and the fact that few studies have been conducted that have found significant differences in efficacy among oral treatments. All guidelines also agree that oral antihistamines are typically only effective in AD for sedation, if pruritus is disturbing sleep, or if a patient has urticaria or other atopic conditions, such as hay fever, that may benefit from use of these drugs. Of all the guidelines, only the AAD recommendations have specific discussions regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications. Systemic Antimicrobial Therapy
Another difference among the guidelines involves oral antimicrobial therapy. Oral antibiotics are recommended by all the groups if clinical signs of secondary infection exist, but the JTF also suggests a skin culture for methicillin-resistant S aureus before prescribing antibiotics or empirically using antibiotics effective against methicillinresistant S aureus if practicing in an area of known bacterial resistance. The AAD group recommends skin culture only if initial antibiotic therapy has failed, and, furthermore, does not mention specific antibiotics. The other groups do not discuss this point. Last, only the JTF discusses avoiding the smallpox vaccine since it may lead to eczema vaccinatum, although this immunization is not commonly administered in current practice and would be relevant to only a fairly small segment of the population.
gens before intervention. In contrast, the JTF and European groups suggest that patients with AD minimize exposure to aeroallergens without testing, and support the use of strategies to avoid house dust mites. The JTF and European guidelines also concur that immunotherapy to specific allergens is sometimes useful in AD management. Food Allergens
The guidelines also have different views on the role of food allergies. The AAD guidelines do not oppose patients attempting a diagnostic elimination diet for 4 to 6 weeks even before an oral food challenge, although they mention that a placebo-controlled oral food challenge is the criterion standard for diagnosing food allergy and that avoidance diets are “unlikely to affect the course of AD.”7(p9) The European guidelines, while not definitive in their recommendation, seem to favor eliminating only foods that have tested positive with oral provocation. The JTF guidelines, however, promote the use of food-specific IgE antibody testing in patients with food allergy symptoms and recommend an oral food challenge only if results of the IgE testing are negative. Indeed, Thompson et al13 reported that dermatologists are less likely to tell patients with AD that allergy played a role in their disease, and Hanifin14 writes that allergists tend to test for serum IgE too frequently. This is an interesting discrepancy, given that it has been reported that elimination diet with a food challenge test was used more often by allergists than by dermatologists.1 With regard to environmental patch testing, the AAD supports its use if physicians suspect a component of causing allergic contact dermatitis or in patients with recalcitrant AD. In addition, the AAD asserts that positive results of patch testing should be confirmed by improvement of symptoms after the avoidance of suspected allergens. However, environmental patch testing is minimally discussed by the JTF and not at all by the other 2 groups. Vitamin D
Preventive Measures and Alternative Therapies There are substantive differences observed among the guidelines regarding supplementary methods to control AD, including preventive measures and alternative medicine.
The AAD and the European group do not recommend vitamin D supplementation for patients with AD, whereas the JTF advocates its use, especially for patients with AD who have low levels or intake of vitamin D. The Asia–Pacific group did not address this issue.
Environmental Modifications
Environmental modifications are another area of significant difference among the guidelines. The JTF parameters recommend several environmental modifications for patients, including controlling temperature and humidity to avoid increased pruritus, avoiding sports that cause intense perspiration or are played in the heat (ie, swimming is preferred), and using nonirritating sunscreen with avoidance of prolonged sun exposure, as well as several clothing modifications (laundering new clothing before wearing, using liquid rather than powder detergent with a second rinse cycle, avoiding tight clothing, and using cotton clothing), while the European guidelines also support the use of smooth clothing and avoiding irritating fabrics. The AAD guidelines conclude there is not enough evidence to support clothing modifications. Aeroallergens
The AAD group says that the role of aeroallergens in AD is controversial and recommends a confirmed diagnosis of specific allerE4
Discussion Overall, the JTF and European guidelines appear to be more amenable to the use of low-risk adjunctive strategies, such as using vitamin D, minimizing exposure to aeroallergens, and implementing other environmental strategies such as clothing modifications, whereas the AAD more often states that if there is little or lowquality evidence supporting such management strategies, they cannot be recommended. Perhaps this pattern exists because allergists are more apt to focus on preventive strategies and triggers of allergic or irritant responses, as their training emphasizes this focus.15 However, this emphasis in allergists’ training does not explain the European dermatologists’ agreement on some of these issues. United States dermatologists appear to relatively de-emphasize allergic or irritant triggers and instead stress avoiding treatment failure caused by nonadherence with antiinflammatory therapies.
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Differences in subtypes of patients seen by the groups, with a bias of those with allergic triggers being seen by allergists and those with more intrinsic AD being seen preferentially by dermatologists, could also help explain these different emphases. While the guidelines all appeared to draw from a similar data set, each noted that there were significant gaps in the evidence, thus leaving room for interpretation based on background and experience.
Conclusions The purpose of this review was twofold. First, we establish that while basic principles of AD management are similar in all the included guidelines, there are noteworthy differences in recommendations, especially regarding adjunctive therapies and ancillary management. These remedies tend to have less supporting evidence, which ARTICLE INFORMATION Accepted for Publication: February 2, 2015. Published Online: April 8, 2015. doi:10.1001/jamadermatol.2015.0250. Author Contributions: Drs Lio and Mohan had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Mohan. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: Mohan. Study supervision: Lio. Conflict of Interest Disclosures: Dr Lio served as a member of the Joint Task Force Atopic Dermatitis Workgroup and is one of the authors of those guidelines. No other disclosures were reported. REFERENCES 1. Saavedra JM, Boguniewicz M, Chamlin S, et al. Patterns of clinical management of atopic dermatitis in infants and toddlers: a survey of three physician specialties in the United States. J Pediatr. 2013;163(6):1747-1753. 2. Henderson RL, Fleischer AB Jr, Feldman SR. Dermatologists and allergists have far more experience and use more complex treatment regimens in the treatment of atopic dermatitis than other physicians. J Cutan Med Surg. 2001;5(3): 211-216.
may engender disagreement regarding their use. Most important, these guidelines underscore areas in which additional study is needed to further our understanding of the best practices to manage this disease. The other purpose of this review was to facilitate integration of knowledge from different guidelines for management of the same disease. Because this article reviews certain aspects of the AAD and JTF parameters and includes comparison with other international AD management guidelines,10-12 health care professionals from different disciplines and areas of the world may be able to not only compare their own AD management strategies but also encounter differing recommendations than they would otherwise come across in their practice. There are other useful AD management strategies that exist, but they were not considered here.15 The juxtaposition of different guidelines can enhance individualization of treatment for a patient with AD by drawing from different disciplines with varying traditions and perspectives.
3. Baron ED, Barzilai D, Johnston G, et al. Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K. Br J Dermatol. 2002;147(4):710-715. 4. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis, section 1: diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2): 338-351. 5. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis, section 2: management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. 6. Sidbury R, Davis DM, Cohen DE, et al; American Academy of Dermatology. Guidelines of care for the management of atopic dermatitis, section 3: management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71 (2):327-349. 7. 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(6):1218-1233. 8. Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013;131(2):295-299.e1-27. 9. Lio PA, Lee M, LeBovidge J, Timmons KG, Schneider L. Clinical management of atopic dermatitis: practical highlights and updates from the atopic dermatitis practice parameter 2012. J Allergy Clin Immunol Pract. 2014;2(4):361-370.
Dermatology and Venereology (EADV); European Federation of Allergy (EFA); European Task Force on Atopic Dermatitis (ETFAD); European Society of Pediatric Dermatology (ESPD); Global Allergy and Asthma European Network (GA2LEN). Guidelines for treatment of atopic eczema (atopic dermatitis), part I. J Eur Acad Dermatol Venereol. 2012;26(8): 1045-1060. 11. Ring J, Alomar A, Bieber T, et al; European Dermatology Forum; European Academy of Dermatology and Venereology; European Task Force on Atopic Dermatitis; European Federation of Allergy; European Society of Pediatric Dermatology; Global Allergy and Asthma European Network. Guidelines for treatment of atopic eczema (atopic dermatitis), part II. J Eur Acad Dermatol Venereol. 2012;26(9):1176-1193. 12. Rubel D, Thirumoorthy T, Soebaryo RW, et al; Asia–Pacific Consensus Group for Atopic Dermatitis. Consensus guidelines for the management of atopic dermatitis: an Asia–Pacific perspective. J Dermatol. 2013;40(3):160-171. 13. Thompson MM, Tofte SJ, Simpson EL, Hanifin JM. Patterns of care and referral in children with atopic dermatitis and concern for food allergy. Dermatol Ther. 2006;19(2):91-96. 14. Hanifin JM. Atopic dermatitis nomenclature variants can impede harmonization. J Invest Dermatol. 2012;132(2):472-473. 15. Shi VY, Nanda S, Lee K, Armstrong AW, Lio PA. Improving patient education with an eczema action plan: a randomized controlled trial. JAMA Dermatol. 2013;149(4):481-483.
10. Ring J, Alomar A, Bieber T, et al; European Dermatology Forum (EDF); European Academy of
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Review
Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management Girish C. Mohan, BS; Peter A. Lio, MD
IMPORTANCE Atopic dermatitis (AD) is a common skin condition treated by dermatologists,
allergists, pediatricians, and primary care physicians. Several treatment guidelines and therapeutic parameters exist for the management of this disease. Health care professionals may be unaware of guidelines created by specialty organizations other than their own. OBJECTIVE To review, compare, and contrast the most recent AD management guidelines. EVIDENCE REVIEW The guidelines for AD management published by the American Academy of Dermatology 2014 work group were compared with those created by the 2012 Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. International guidelines created by the 2012 European Task Force on Atopic Dermatitis and the 2013 Asia–Pacific Consensus Group for Atopic Dermatitis were also considered. FINDINGS Several differences among the guidelines suggest that there may be disparity in the perceptions of AD between US dermatologists and allergists and health care professionals in other areas of the world. There are notable differences among the guidelines regarding the recommendations for the use of diluted bleach baths, vitamin D, and environmental modifications. CONCLUSIONS AND RELEVANCE Comparison of different guidelines may ultimately augment knowledge of treatment strategies and enhance realization of biases in the understanding and management of AD. JAMA Dermatol. doi:10.1001/jamadermatol.2015.0250 Published online April 8, 2015.
A
topic dermatitis (AD) is a chronic, inflammatory skin condition commonly treated by dermatologists, allergists, pediatricians, and family practitioners. As the pathogenesis of AD is complex and multifactorial, there are many different therapies. In addition, there is evidence that subtypes of AD exist with distinct pathogeneses, consequently requiring different approaches to management. Management of AD addresses a wide variety of issues, ranging from handling acute exacerbations to modifying environmental exposures. Different groups of physicians treating AD may have different strategies and outcomes. Saavedra et al1 reported that allergists were more likely than dermatologists to prescribe elimination diets and use dietary change alone as therapy. Henderson et al2 showed that dermatologists were more likely than other physicians to use topical corticosteroids (TCS), especially high-potency agents. Even within dermatology there is some discrepancy: Japanese dermatologists were less likely to use TCS and more likely to use alternative treatments than were their colleagues in the United States or United Kingdom.3
Author Affiliations: Currently a medical student at University of Illinois College of Medicine, Chicago (Mohan); Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Lio); Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Lio). Corresponding Author: Peter A. Lio, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, 1455 N Milwaukee Ave, Second Floor, Chicago, IL 60622 ([email protected]).
Updated treatment guidelines to help direct physicians in the management of this multifaceted condition allow comparison of approaches to disease management. We review these guidelines to highlight potentially important differences among the guidelines, which could suggest variations in conceptualization of the disorder between allergists and dermatologists, and/or highlight biases regarding the subtypes of patients with AD.
Methods Published guidelines from the following organizations were reviewed: 1. The American Academy of Dermatology (AAD)4-7 2. The Joint Task Force on Practice Parameters (JTF), representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology8,9 3. The 2012 European Task Force on Atopic Dermatitis10,11
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Guidelines for Atopic Dermatitis Management
4. The 2013 Asia–Pacific Consensus Group for Atopic Dermatitis12 Both of us reviewed the guidelines and their similarities and differences (Box and Table). Any differences were resolved by discussion. Each organization had distinct approaches to developing their respective guidelines: The AAD performed a systematic search of PubMed, the Cochrane Library, and the Global Resources for Eczema Trials databases using a number of medical subject headings (eg, atopic dermatitis, topical corticosteroid, nonpharmacologic, calcineurin inhibitor) limited to the English language, and used the strength of the recommendation taxonomy to grade the evidence. A total of 246 articles were included in the review, and evidence tables were used by the work group to develop the recommendations. Expert opinion was relied on in situations where evidence was not available. The JTF performed a systematic literature review of PubMed and the Cochrane Database using a number of medical subject headings (eg, atopic dermatitis/atopic eczema, diagnosis, management, immunomodulating agents), and a classification of recommendations and evidence was used to grade the evidence. A consensus expert opinion on each section was obtained before publication. The European Task Force on Atopic Dermatitis evaluated existing evidence-based guidelines using the Appraisal of Guidelines Research and Evaluation method. They also searched the newer literature
Box. Similarities Among Recommendations From AAD Guidelines,4-7 JTF Guidelines,8,9 European Guidelines,10,11 and Asia–Pacific Guidelines12 Regarding AD Management Similarities Among the Guidelines Topical Therapies
Emollients, topical corticosteroids, and topical calcineurin-inhibitors are mainstays of management Not enough evidence to definitively recommend specialty emollients (eg, ceramide-dominant preparations) Maintenance therapy with topical corticosteroids or topical calcineurin-inhibitors can be used to prevent flares Wet wraps or dressings with topical corticosteroids can be recommended, especially during disease flares No role for topical antihistamines Systemic Therapies
Phototherapy and oral immunomodulatory therapies are to be used for chronic AD recalcitrant to topical therapy No significant differences in efficacy among oral treatment options (cyclosporine, methotrexate, azathioprine, mycophenolate mofetil) have been clearly demonstrated Oral antihistamines are useful for sedation if sleep is disturbed; not recommended on a regular basis for itch Oral antibiotics recommended if clinically overt secondary infection is present Other Management Considerations
Educational interventions regarding managing their disease (eg, videos, written instructions) may help patients Abbreviations: AAD, American Academy of Dermatology; AD, atopic dermatitis; JTF, Joint Task Force.
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using MEDLINE, EMBASE, and the Cochrane Library. Consensus was reached using the Delphi method. An external review by all European dermatologic societies was also performed before publication. Evidence was systematically graded and classified by strength. The Asia–Pacific Consensus Group for Atopic Dermatitis represented evidence- and experience-based recommendations aimed at physicians in the Asia–Pacific region, but did not elaborate on their approach to gathering the data and did not grade the evidence explicitly in the guideline document.
Results There was disparity among the groups in terms of the approach to gathering and grading the evidence. However, all appeared to acknowledge the relatively large gaps in high-quality evidence and the necessity to use lower-quality studies and clinical experience to develop a comprehensive guideline.
Topical Therapy Topical Emollients and Anti-Inflammatory Therapy
All the management guidelines review topical therapy for AD. The guidelines agree on the basic tenets of AD management such as using emollients as first-line therapy, with inconclusive evidence that specialized moisturizers, such as ceramide-dominant preparations, are more effective than others. All the guidelines similarly recommend the use of TCS as initial anti-inflammatory therapy and the use of topical calcineurin inhibitors in specific situations, such as for eczema on the face or eyelids or for proactive maintenance therapy to prevent flares. All the guidelines also recommend wet-wrap therapy with TCS for severe manifestations of disease and find no role for topical antihistamines (Box). Several differences among the guidelines do exist, however. The AAD group discusses combination TCS and topical calcineurin inhibitor therapy being potentially more efficacious than either used alone and the European Task Force specifically recommends against combination therapy, concluding that it is not useful, while the other groups remain silent on this point (Table). The “soak and smear technique” with topical anti-inflammatories for severely inflamed lesions was endorsed by the AAD and the Asia–Pacific groups, while the JTF only mentioned applying moisturizer after soaking in water. Notably, the AAD and Asia–Pacific guidelines promote physicians counseling patients against incorrect beliefs about TCS (ie, fear of corticosteroid use) to prevent poor efficacy of treatment owing to nonadherence; this issue is not broached by the JTF or the European group. Topical Antimicrobial Therapy
The AAD group concluded that patients with moderate to severe AD with frequent bacterial infections could benefit from diluted bleach baths. The European Task Force and Asia–Pacific group also endorse the use of diluted bleach baths, while the JTF is less conclusive about this therapy, stating that bleach baths require more study and that the most appropriate AD subtype that would benefit from this treatment remains unclear (Table). The JTF articulates, however, that the use of antiseptics (eg, triclosan and chlorhexidine gluconate) may help patients with excessive Staphylococcus aureus
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Table. Differences Among Recommendations From AAD Guidelines, JTF Guidelines, European Guidelines, and Asia–Pacific Guidelines Regarding AD Management Guideline AAD4-7
JTF8,9
European10,11
Asia-Pacific12
TCS + TCI combination
Combination TCS and TCI therapy may be more effective than either alone
Not discussed
Recommend against combination TCS and TCI therapy, concluding it is not useful
Not discussed
“Soak and smear” technique
Soak and smear technique with TCS or TCI recommended
Soak and smear technique with moisturizer recommeded
Not discussed
Soak and smear technique with TCS recommended
Fear of corticosteroid use
Promotes counseling patients regarding fear of corticosteroid use
Not discussed
Not discussed
Disucsses a need to address concerns regarding fear of corticosteroid use
Bleach baths
Bleach baths effective as therapy Bleach baths are promising but require more study to decolonize Staphylococcus aureus
Bleach baths appear to be useful in reducing AD severity
Bleach baths effective in patients with AD who have secondary bacterial infection
Topical antiseptics
Topical antiseptics not supported as they provide no benefit
Topical antiseptics can be used to control S aureus colonization
Topical antiseptics may be considered but may not help
Topical antiseptics not supported as they provide no benefit
Topical tar
Not enough data to recommend topical tar use
Topical tar may be of benefit but should not be used on acutely inflamed skin
Not discussed
Not discussed
Oral medications
Tabulates recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral immunomodulatory therapies
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Recommendations regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications of oral therapies not tabulated
Antibiotics for secondary infection, with or without skin culture
Skin culture if initial antibiotic therapy fails
Suggest skin culture for methicillin-resistant S aureus before initially prescribing antibiotics
Not discussed
Not discussed
Treatment Topical Therapies
Systemic Therapies
Other Management Considerations Silver-impregnated clothing and silk clothing
Efficacy of silver-impregnated or Silver-impregnated clothing or silk clothing unclear silk clothing may help patients
Silver-impregnated clothing or Not discussed silk clothing may help patients
Bath additives
Not enough evidence to support bath additives
Bath additives (eg, oatmeal and baking soda) may have antipruritic effects
Not discussed
Emollient additives may be used while bathing
Vitamin D
Not enough evidence to recommend vitamin D use
Supports vitamin D use
Not enough evidence to recommend vitamin D use
Not discussed
Environmental modifications
Not enough evidence to support laundry modifications; temperature and humidity modifications not discussed
Recommend environmental modifications (temperature and humidity control and laundry modifications)
Avoiding irritating fabrics and occlusive clothing is recommended
Not discussed
Aeroallergens
Testing needed before aeroallergen minimization indicated; supports only house dust mite covers
Supports minimizing exposure to aeroallergens without testing and use of house dust mite covers, weekly bedding washes, and removing carpeting
Supports minimizing exposure to house dust mites without testing
Not discussed
Allergen-specific immunotherapy
Not enough evidence to support immunotherapy
Testing needed before using immunotherapy to specific allergens
Testing needed before using immunotherapy to specific allergens
Not discussed
Food allergy testing
Supports diagnostic elimination diet for 4-6 weeks or controlled oral food challenge if specific food allergy suspected clinically
Recommends food-specific IgE testing if specific food allergy suspected clinically; oral food challenge only if IgE test results are negative
Recommends controlled oral food challenge if specific food allergy suspected clinically
Not discussed
Psychological care
Not discussed
Recommends psychological evaluation and treatment for patients with emotional distress if it is affecting treatment adherence
Psychosomatic counseling can be helpful for patients
Not discussed
Abbreviations: AAD, American Academy of Dermatology; AD, atopic dermatitis; JTF, Joint Task Force; TCI, topical calcineurin-inhibitors; TCS, topical corticosteroids.
colonization, in agreement with the European guidelines that also place antiseptics in their recommendations. The AAD directly opposes this recommendation by stating they did not find any clear benefit for topical antibiotics/antiseptics, in accord with the Asia– Pacific group.
Other Topical Therapies
Other differences in topical therapy recommendations include the JTF and Asia–Pacific groups suggesting that additives in bathwater (eg, oatmeal and emollients) may have beneficial effects. On the other hand, the AAD group does not promote the use of bath addi-
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tives because they found no convincing supportive evidence of their effectiveness, while the European guidelines do not discuss them at all.
Oral and Systemic Therapy The guidelines also provide recommendations on oral and systemic therapies for AD (Table). All agree that oral and systemic therapies are to be used for chronic AD recalcitrant to proper skin care and topical therapies. All the guidelines discuss many of the same therapies that may be used (eg, phototherapy, cyclosporine, methotrexate, azathioprine, and systemic corticosteroids) and the fact that few studies have been conducted that have found significant differences in efficacy among oral treatments. All guidelines also agree that oral antihistamines are typically only effective in AD for sedation, if pruritus is disturbing sleep, or if a patient has urticaria or other atopic conditions, such as hay fever, that may benefit from use of these drugs. Of all the guidelines, only the AAD recommendations have specific discussions regarding dosing, adverse effects, baseline and follow-up testing, drug interactions, and contraindications. Systemic Antimicrobial Therapy
Another difference among the guidelines involves oral antimicrobial therapy. Oral antibiotics are recommended by all the groups if clinical signs of secondary infection exist, but the JTF also suggests a skin culture for methicillin-resistant S aureus before prescribing antibiotics or empirically using antibiotics effective against methicillinresistant S aureus if practicing in an area of known bacterial resistance. The AAD group recommends skin culture only if initial antibiotic therapy has failed, and, furthermore, does not mention specific antibiotics. The other groups do not discuss this point. Last, only the JTF discusses avoiding the smallpox vaccine since it may lead to eczema vaccinatum, although this immunization is not commonly administered in current practice and would be relevant to only a fairly small segment of the population.
gens before intervention. In contrast, the JTF and European groups suggest that patients with AD minimize exposure to aeroallergens without testing, and support the use of strategies to avoid house dust mites. The JTF and European guidelines also concur that immunotherapy to specific allergens is sometimes useful in AD management. Food Allergens
The guidelines also have different views on the role of food allergies. The AAD guidelines do not oppose patients attempting a diagnostic elimination diet for 4 to 6 weeks even before an oral food challenge, although they mention that a placebo-controlled oral food challenge is the criterion standard for diagnosing food allergy and that avoidance diets are “unlikely to affect the course of AD.”7(p9) The European guidelines, while not definitive in their recommendation, seem to favor eliminating only foods that have tested positive with oral provocation. The JTF guidelines, however, promote the use of food-specific IgE antibody testing in patients with food allergy symptoms and recommend an oral food challenge only if results of the IgE testing are negative. Indeed, Thompson et al13 reported that dermatologists are less likely to tell patients with AD that allergy played a role in their disease, and Hanifin14 writes that allergists tend to test for serum IgE too frequently. This is an interesting discrepancy, given that it has been reported that elimination diet with a food challenge test was used more often by allergists than by dermatologists.1 With regard to environmental patch testing, the AAD supports its use if physicians suspect a component of causing allergic contact dermatitis or in patients with recalcitrant AD. In addition, the AAD asserts that positive results of patch testing should be confirmed by improvement of symptoms after the avoidance of suspected allergens. However, environmental patch testing is minimally discussed by the JTF and not at all by the other 2 groups. Vitamin D
Preventive Measures and Alternative Therapies There are substantive differences observed among the guidelines regarding supplementary methods to control AD, including preventive measures and alternative medicine.
The AAD and the European group do not recommend vitamin D supplementation for patients with AD, whereas the JTF advocates its use, especially for patients with AD who have low levels or intake of vitamin D. The Asia–Pacific group did not address this issue.
Environmental Modifications
Environmental modifications are another area of significant difference among the guidelines. The JTF parameters recommend several environmental modifications for patients, including controlling temperature and humidity to avoid increased pruritus, avoiding sports that cause intense perspiration or are played in the heat (ie, swimming is preferred), and using nonirritating sunscreen with avoidance of prolonged sun exposure, as well as several clothing modifications (laundering new clothing before wearing, using liquid rather than powder detergent with a second rinse cycle, avoiding tight clothing, and using cotton clothing), while the European guidelines also support the use of smooth clothing and avoiding irritating fabrics. The AAD guidelines conclude there is not enough evidence to support clothing modifications. Aeroallergens
The AAD group says that the role of aeroallergens in AD is controversial and recommends a confirmed diagnosis of specific allerE4
Discussion Overall, the JTF and European guidelines appear to be more amenable to the use of low-risk adjunctive strategies, such as using vitamin D, minimizing exposure to aeroallergens, and implementing other environmental strategies such as clothing modifications, whereas the AAD more often states that if there is little or lowquality evidence supporting such management strategies, they cannot be recommended. Perhaps this pattern exists because allergists are more apt to focus on preventive strategies and triggers of allergic or irritant responses, as their training emphasizes this focus.15 However, this emphasis in allergists’ training does not explain the European dermatologists’ agreement on some of these issues. United States dermatologists appear to relatively de-emphasize allergic or irritant triggers and instead stress avoiding treatment failure caused by nonadherence with antiinflammatory therapies.
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Differences in subtypes of patients seen by the groups, with a bias of those with allergic triggers being seen by allergists and those with more intrinsic AD being seen preferentially by dermatologists, could also help explain these different emphases. While the guidelines all appeared to draw from a similar data set, each noted that there were significant gaps in the evidence, thus leaving room for interpretation based on background and experience.
Conclusions The purpose of this review was twofold. First, we establish that while basic principles of AD management are similar in all the included guidelines, there are noteworthy differences in recommendations, especially regarding adjunctive therapies and ancillary management. These remedies tend to have less supporting evidence, which ARTICLE INFORMATION Accepted for Publication: February 2, 2015. Published Online: April 8, 2015. doi:10.1001/jamadermatol.2015.0250. Author Contributions: Drs Lio and Mohan had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Mohan. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: Mohan. Study supervision: Lio. Conflict of Interest Disclosures: Dr Lio served as a member of the Joint Task Force Atopic Dermatitis Workgroup and is one of the authors of those guidelines. No other disclosures were reported. REFERENCES 1. Saavedra JM, Boguniewicz M, Chamlin S, et al. Patterns of clinical management of atopic dermatitis in infants and toddlers: a survey of three physician specialties in the United States. J Pediatr. 2013;163(6):1747-1753. 2. Henderson RL, Fleischer AB Jr, Feldman SR. Dermatologists and allergists have far more experience and use more complex treatment regimens in the treatment of atopic dermatitis than other physicians. J Cutan Med Surg. 2001;5(3): 211-216.
may engender disagreement regarding their use. Most important, these guidelines underscore areas in which additional study is needed to further our understanding of the best practices to manage this disease. The other purpose of this review was to facilitate integration of knowledge from different guidelines for management of the same disease. Because this article reviews certain aspects of the AAD and JTF parameters and includes comparison with other international AD management guidelines,10-12 health care professionals from different disciplines and areas of the world may be able to not only compare their own AD management strategies but also encounter differing recommendations than they would otherwise come across in their practice. There are other useful AD management strategies that exist, but they were not considered here.15 The juxtaposition of different guidelines can enhance individualization of treatment for a patient with AD by drawing from different disciplines with varying traditions and perspectives.
3. Baron ED, Barzilai D, Johnston G, et al. Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K. Br J Dermatol. 2002;147(4):710-715. 4. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis, section 1: diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2): 338-351. 5. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis, section 2: management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132. 6. Sidbury R, Davis DM, Cohen DE, et al; American Academy of Dermatology. Guidelines of care for the management of atopic dermatitis, section 3: management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71 (2):327-349. 7. 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(6):1218-1233. 8. Schneider L, Tilles S, Lio P, et al. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013;131(2):295-299.e1-27. 9. Lio PA, Lee M, LeBovidge J, Timmons KG, Schneider L. Clinical management of atopic dermatitis: practical highlights and updates from the atopic dermatitis practice parameter 2012. J Allergy Clin Immunol Pract. 2014;2(4):361-370.
Dermatology and Venereology (EADV); European Federation of Allergy (EFA); European Task Force on Atopic Dermatitis (ETFAD); European Society of Pediatric Dermatology (ESPD); Global Allergy and Asthma European Network (GA2LEN). Guidelines for treatment of atopic eczema (atopic dermatitis), part I. J Eur Acad Dermatol Venereol. 2012;26(8): 1045-1060. 11. Ring J, Alomar A, Bieber T, et al; European Dermatology Forum; European Academy of Dermatology and Venereology; European Task Force on Atopic Dermatitis; European Federation of Allergy; European Society of Pediatric Dermatology; Global Allergy and Asthma European Network. Guidelines for treatment of atopic eczema (atopic dermatitis), part II. J Eur Acad Dermatol Venereol. 2012;26(9):1176-1193. 12. Rubel D, Thirumoorthy T, Soebaryo RW, et al; Asia–Pacific Consensus Group for Atopic Dermatitis. Consensus guidelines for the management of atopic dermatitis: an Asia–Pacific perspective. J Dermatol. 2013;40(3):160-171. 13. Thompson MM, Tofte SJ, Simpson EL, Hanifin JM. Patterns of care and referral in children with atopic dermatitis and concern for food allergy. Dermatol Ther. 2006;19(2):91-96. 14. Hanifin JM. Atopic dermatitis nomenclature variants can impede harmonization. J Invest Dermatol. 2012;132(2):472-473. 15. Shi VY, Nanda S, Lee K, Armstrong AW, Lio PA. Improving patient education with an eczema action plan: a randomized controlled trial. JAMA Dermatol. 2013;149(4):481-483.
10. Ring J, Alomar A, Bieber T, et al; European Dermatology Forum (EDF); European Academy of
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