Clinical Insights About Topical Treatment of Mild-to-Moderate Pediatric and Adult Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition, also referred to as atopic eczema, that is identified by itching and recurrent eczematous lesions. It often starts in infancy where it affects up to 20% of children but is also highly prevalent in adults. AD inflicts a significant psychosocial burden on patients and their families and increases the risk of other immune-mediated inflammatory conditions, such as asthma and allergic rhinitis, food allergy, and mental health disorders. It is a lifelong condition associated with epidermal barrier dysfunction and altered immune function. Through the use of emollients and anti-inflammatory agents, current prevention and treatment therapies attempt to restore epidermal barrier function. Acute flares are treated with topical corticosteroids. Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCSs) are used for proactive treatment to prevent remission. There remains a need and opportunity to improve AD care through future research directed toward an improved understanding of the heterogeneity of the disease and its subtypes, the role of autoimmunity in its pathogenesis, the mechanisms behind disease-associated itch and response to specific allergens, and the comparative effectiveness and safety of therapies.

Keywords

atopic dermatitis atopic eczema clinical guidelines

Introduction

Atopic dermatitis (AD) is a common pruritic chronic inflammatory skin disease that presents with relapsing and remitting cycles and significantly burdens patients’ quality of life (QoL).¹ AD affects more than 20% of children and up to 3.5% of adults in many countries and its prevalence is on the rise, especially in the developing world.^2,3 AD prevalence appears to have plateaued in certain developed countries, including New Zealand and the United Kingdom, but continues to rise in lower-income areas, including South East Asia and Latin America, specifically in young children aged 6-7 years.³ AD prevalence varies across race/ethnicity and region as evidenced by its higher incidence in African American children (17.3%) compared with Caucasian children (10.4%); however, the role of race and ethnicity in the pathophysiology of AD remains unclear.^4-6 AD has a multifactorial etiology including immune system dysfunction, skin barrier disorders, genetics, and environmental factors.^7,8 However, the interaction among these factors is poorly understood.⁷ It is imperative to the success of AD management to treat both the epidermal barrier defect and inflammation present in many AD cases.⁹ Recent advances in the knowledge of the immunopathogenesis of AD are promising and expected to yield new therapeutic targets and opportunities for patients.¹⁰ This paper aims to explore recent advances in the treatment of mild-to-moderate AD and develop consensus on the topical treatment of mild-to-moderate AD.

Methods

An expert panel of 9 dermatologists and pediatricians who commonly treat AD patients was convened October 29, 2017, to develop evidence-based consensus treatment recommendations for the topical management of mild-to-moderate AD in pediatric and adult patient populations. The treatment of other forms of dermatitis such as allergic contact dermatitis and irritant dermatitis was beyond the scope of this work. Likewise, the treatment of severe AD and the use of systemic treatment for AD were not included in the scope of this work.

Evidence coupled with the expert opinion and experience of the panel was used to define and address current clinical challenges in the clinical care of mild-to-moderate AD and to develop 15 key statements or recommendations for clinicians to optimize treatment and improve outcomes. The consensus process consisted of a nominal group technique and a Delphi approach.¹¹ Statements were developed based on AD guidelines literature identified prior to the meeting. The panel reached unanimous consensus through 9 blinded reiterations and votes to define the 15 final statements and key points used for discussion in this paper.

Literature Review

Literature describing current best practice in AD treatment was identified in a search prior to the expert panel meeting. Using clinically relevant selected literature, premeeting statements were developed that addressed multidisciplinary aspects of AD management and used validated AD classification systems such as Severity Scoring of Atopic Dermatitis¹² and the Eczema Area and Severity Index.¹³ Guidelines included for discussion were the most current, dated from 2012 to 2016 (Table 1).

Table 1.

Selected Guidelines and Clinical Care Pathways.

Association, Year, Country	Document Title	Contributors
AAD 2014, United States¹⁴	Section 2: Management and treatment of AD with topical therapies	United States/United Kingdom/Canada dermatologists
EADV 2012, EU^15,16	Guidelines for treatment of AD Part I Guidelines for treatment of AD Part II	EU allergists and dermatologists
JDA 2016, Japan¹⁷	Clinical practice guidelines for the management of AD	Japanese dermatologists
Eczema Society of Canada/Société canadienne de l’eczéma 2016, Canada¹⁸	Practical guideline to management of AD	Canadian dermatologists
Not applicable 2016, Canada¹⁹	Case-Based clinical pathway	Canadian dermatologists
ETFAD/EADV AD task force²⁰	Position paper adult and pediatric AD patients, 2015	EU allergists and dermatologists

AAD, American Academy of Dermatology; AD, atopic dermatitis; EADV, European Academy of Dermatology and Venereology; ETFAD, European Task Force on Atopic Dermatitis; EU, European Union; JDA, Japanese Dermatological Association.

Results of the search indicate guidelines for the topical treatment of AD have not changed significantly over the past 10 years. Evidence from the review suggests there is more heterogeneity in topical treatment guidelines and practices for the pediatric AD population^17,21,22 than those for adult AD.^14,15,18-20 For example, TCIs are recommended by the American Academy of Dermatology⁷ and European Academy of Dermatology and Venereology^15,16 endorsed guidelines, but not by the Japanese Dermatological Association¹⁷ guidelines.

Results of the Panel Discussions and Consensus Statements

Subsequently, the expert panel discussed, adapted, and voted on the preestablished statements, as well as ones the panel added, and established the consensus statements for best practice in AD treatment.

Statement 1: AD is a common chronic inflammatory skin disease that presents with relapsing and remitting cycles and affects patients’ QoL.

AD diagnosis starts with a detailed patient history, including ascertainment of family history of atopy (AD, allergic rhinitis, and asthma), known allergies, and exposure profile.²³ This is followed by a physical examination of the patient’s skin to determine the extent of the AD and estimating the percentage of involvement, while severity is determined by grading specific signs of presenting eczema (eg, oozing, scaling, crusting, erythema, edema, lichenification).¹³

In clinical practice, severity should take into account patient criteria such as how AD affects their ability to carry out daily activities and functions, how it affects their QoL, and appearance of lesions and affected body surface area.^20,23 AD flare-ups significantly affect patients’ physical and psychosocial well-being and are associated with high levels of sleep deprivation, stigmatization, social withdrawal, anxiety, and depression.²⁴ Anxiety in people with AD is of particular concern, as psychological stress has been found to trigger the itch-scratch cycle and can precipitate or exacerbate AD leading to flares and abnormal skin barrier function.^24,25 In a study involving 318 AD patients age 4 to 70 years, patients were reported to have significantly lower vitality, social functioning, and mental health than the general population.²⁵ In addition, study participants had statistically lower mental health scores than patients with other chronic illnesses including hypertension and diabetes.²⁵ An international study involving 2002 patients age 13 years and older with moderate to severe AD reported more than 33% of the patients have lower self-confidence because of their condition.²⁶ The same survey found approximately 50% of patients experience depression, unhappiness, and anxiety about the next exacerbation even when in remission.²⁶ Seventy-five per cent (75%) of patients and their caregivers feel that being able to effectively control AD would be the single most important improvement in their QOL.²⁶ For these reasons, it is important AD assessment focus both on physical and QoL aspects of the disease for optimal AD management.

Statement 2: Age, ethnicity, genetics, comorbidities, and burden of disease influence the experience of living with AD.

AD is a common condition in infancy that may disappear by age 3 years in most children.¹⁶ The prognosis is mostly determined by severity, exposure, and sensitization to allergens, the presence of rhinitis, and a positive family history of atopy.²⁷ Up to 70% of AD patients have been reported to have a positive family history of atopic disease and display alterations in epidermal barrier genes (eg, filaggrin, loricrin, involucrin).⁷ The early identification and avoidance of sensitizing allergens coupled with emollient therapy to improve skin barrier function at a young age are therefore extremely important for limiting its progression and impact on the patient as well the population.

AD prevalence continues to vary and change in different regions of the world. Nigeria, the United Kingdom, New Zealand, and, more recently, Latin America, are currently the areas with the highest childhood prevalence, with a prevalence of about 20%, whereas China and India report the lowest prevalence of 0.2% and 0.9%, respectively.³ Environmental risk factors associated with increased prevalence include higher socioeconomic status, higher level of family education, smaller family size, and urban environment.²⁸

Research indicates the adult prevalence of AD is up to 3.5% in Canada, is generally lower for men vs women, and decreases with age, while severity varies by scale and region.³ However, regardless of age or region, the majority of AD cases in children and adults are mild, while severe cases average between 10% and 20% in children and are slightly higher in the adult population.^3,15

Statement 3: Itch and sleep disturbances are important issues for patients with AD.

Patients with AD frequently experience sleep disturbances that have been shown to be directly related to the severity of pruritus. A 2006 study of 76 patients from general practitioner and dermatologist practices found that more than 50% of patients suffered from sleep disturbance due to pruritus.²⁹ Pruritus and its associated lack of sleep can significantly decrease AD patients’ QoL. A prospective cross-sectional and matched study³⁰ of 1356 adult outpatients with chronic urticaria, psoriasis. or AD showed AD significantly impedes sleep, physical comfort, and daily activities. Of the 386 AD patients included in the study, 46% reported “often” having difficulty with sleep while 10% of patients experienced difficulties sleeping on a daily basis. AD was reported to affect physical comfort more than urticaria or psoriasis (P < .001) and affect daily activities more than psoriasis (P < 0.001).³⁰

Antihistamines have been used to relieve itching in AD patients in past decades, despite there being limited data to support their use.¹⁵ The few randomized trials that have been conducted both with first- and second-generation antihistamines show little or no effect in decreasing pruritus.^15,20 First-generation antihistamines such as hydroxyzine may facilitate sleep better than newer, less-sedating second-generation antihistamines in acute situations during flares but do affect sleep quality.²⁰ As such, guidelines do not support their use for the treatment of pruritus and caution against long-term use for sleep disturbances.^15,18

Statement 4: Patient and/or caregiver education is an essential aspect of AD management.

Patient and caregiver education is a key aspect of effective AD control and should be viewed as a type of intervention in itself that can improve therapeutic outcomes. Although effective treatments for AD are available, outcomes are often limited by poor adherence to treatment plans. It is important for patients and caregivers to understand the chronic relapsing-remitting nature of AD, how to cleanse and hydrate the skin, apply moisturizers and topical medications, when to seek medical advice, how to avoid irritants and triggers, and when to step up or step down treatment for treatment to be successful.^18,31 Education should start with a clear, written treatment plan and continue with each follow-up visit to ensure the plan is well understood and adhered to.³¹ Discussion and individualized, written care plans should provide the opportunity for patients to identify and plan ways to avoid their triggers and be actively involved in their care plan.¹⁸ Educational approaches that utilize a number of different methods and tools such as videos, pamphlets, and support groups, to facilitate the transfer of knowledge and skills to patients and their caregivers have been demonstrated to improve outcomes such as AD disease severity, treatment adherence, QoL, and coping with itch.³²

AD action plans are available from some eczema organizations^18,33 as well as handouts for the topical anti-inflammatory management of AD to facilitate patient and caregiver education.³⁴

Statement 5: Most patients have mild-to-moderate disease, which usually responds to topical therapy.

It is estimated that approximately two-thirds of AD patients have mild disease, 26% moderate, and 7% severe disease.³⁵ Although it is common practice for pediatric patients to be referred and treated by dermatologists or pediatricians, most cases can be adequately treated by primary care physicians with the use of topical anti-inflammatory therapy. Whether patients are referred to a dermatologist, pediatrician, or allergist, family practitioners play a central role in AD care, follow-up, and ongoing patient/caregiver education.³¹

Statement 6: Regular use of moisturizers and avoidance of triggers are recommended as the foundation of management for all patients with AD, regardless of disease severity.

Moisturizers remain the cornerstone of treatment for all severities of AD to counter and control the xerosis, decrease epidermal water loss, and improve the dysfunctional epidermal barrier.¹⁴ A Cochrane review³⁶ with a focus on moisturizers that contained humectants, lipids, and/or ceramides (or their precursors)³⁷ reported their daily use reduced the rate of flares and enhanced the efficacy of topical steroid treatment. The panel agreed with established guidelines^14-20,23 supporting the daily use of moisturizers, alone or in combination with other therapy, for all AD patients to prevent itching, reduce flare frequency, and restore the lipid balance of the skin. In accordance with established guidelines, the panel acknowledged the application of moisturizers should be liberal and frequent, and the choice of moisturizer will be dependent on individual preference but ideally should be effective, inexpensive, and free of potentially sensitizing agents. Moisturizers should also be applied soon after bathing, to improve skin hydration.¹⁴ Although the frequency of bathing is controversial, short-duration warm baths are recommended for all patients with AD as part of standard care, immediately followed by adequate application of moisturizer to damp skin.^14-17,20 Dilute bleach baths (using one-half cup sodium hypochlorite per full bath or 1 mL/L) twice weekly may be recommended for patients with recurrent skin infections.^15,31

Statement 7: When routine moisturizing does not control symptoms, anti-inflammatory topical therapy should be added and continued until control is achieved.

If moisturizers and avoidance of triggers is not sufficient, topical anti-inflammatory agents, such as TCSs or TCIs, are recommended and should be applied to involved skin daily or twice per day until clear, while moisturizers should continue to be applied to all areas.^{14-17,23,38,39} TCSs are the most widely used first-line anti-inflammatory option and are available in a variety of strengths from mild (group I) to potent and very potent (groups III and IV).²⁰ Super-potent TCSs are not recommended for mild-to-moderate AD, especially in children. There seems to be no consensus regarding what agent, strength, or dose of TCS to use for the treatment of flares, as there are limited controlled, comparative studies with TCS products.^14,40,41 Once-daily use of a potent TCS for 3-6 days is usually sufficient for treatment of flares, followed by a quick taper in potency (see Figures 1 and 2).^15,20 Another common practice is to use the lowest-potency agent thought to be needed and adjust upward only if it fails.¹⁴

If topical TCS or TCI treatment does not manage to control AD inflammation, phototherapy may be helpful to get the disease under control, while continuing topical products.²⁰

Statement 8: Patient age, location/appearance/extent of lesions, response to previous therapy, and patient preferences should be considered when choosing a topical anti-inflammatory treatment for AD.

There is a multitude of formulations of topical anti-inflammatory treatments. The broad categories are ointments, oils, creams, lotions, gels, foams, and sprays.¹⁰ Gels, foams, and sprays are more recent developments and may lead to enhanced medication delivery. Cream and ointment formulations, however, are commonly available in generic form and are thus the best options for patients with financial constraints. In general, for eroded lesions or nonintact skin, ointments, or oils are preferred as they do not contain the preservatives required to stabilize other formulations that may cause burning or stinging of the patient’s skin.¹⁰ Ointments are generally also more potent than their equivalent amount in other formulations and so are very effective in the treatment of drier areas of the body, including palms and soles.¹⁰ Foams, sprays, and gels are generally more appealing to use on hair-bearing areas such as the scalp and on oily skin areas, such as the face.¹⁰ Sprays are also good for locations that might be widespread or difficult to reach.

Low-potency TCS products are considered appropriate for face and folds and for the very young, while high-potency TCSs are generally not used in AD unless the lesions are very chronic and lichenified. TCI products, including pimecrolimus cream and tacrolimus ointment, are safe and effective for children older than age 2 years and can be used on all areas of the body and face.²⁰ However, they may not be well tolerated on very inflamed skin.

Statement 9: Patient/caregiver concerns about topical anti-inflammatory therapies (eg, steroid phobia, black box warning) should be addressed.

TCSs are generally safe when used appropriately; however, potential side effects such as skin atrophy, purpura, telangiectasia, striae, focal hypertrichosis, impaired wound healing, allergic contact dermatitis, and acneiform or rosacea-like eruptions on the face can occur, particularly if TCSs are used inappropriately. The potential for these and other side effects, however, may result in a patient’s fear to comply with TCS treatment and should be discussed with the patient to improve adherence and avoid under-treatment.²⁰

Similarly, TCI usage may result in short-term side effects that could negatively affect compliance such as cutaneous viral infections, skin burning, and pruritus, especially when applied to acutely inflamed skin.^14,20 Patients should be advised of these potential side effects to avoid premature discontinuation of treatment. The FDA-issued black box warning on TCIs regarding a possible risk for lymphoma cancer should also be discussed with patients prior to start of treatment.¹⁵ Clinicians should assure patients that no causal relationship has been established between lymphoma cancer and TCI and that 5-year postmarketing surveillance data from 11 000 patients confirm there is no higher incidence of cancer in TCI-exposed patients than in the general population.⁴¹

Statement 10: Maintenance therapy with topical anti-inflammatory agents may reduce flares and should be considered in patients with frequently relapsing disease.

TCSs and TCIs may be used intermittently to maintain control if moisturizers alone do not. TCSs may be used proactively 1-2 times per week or TCIs may be used 2-3 times per week after disease stabilization to prevent recurrences in previously affected skin areas (Figure 1).^{14-20,23,38,39,42} Data from several different trials show proactive therapy with TCSs or TCIs reduces the number of flares and improves the QoL of AD patients and improves mild, moderate AD care.⁴³ The occurrence of side effects does not depend on the proactive or reactive use of the substances, but on the respective potency of the TCIs and TCSs.⁴³ Proactive therapy allows patients to actively control their disease; however, the additional cost associated with long-term maintenance therapy and the need for more frequent medical follow-up may be of concern for some patients and health care providers. These concerns warrant consideration, discussion, and planning to ensure patient adherence and safety.

Statement 11: Patients on long-term TCS therapy should be periodically assessed for potential side effects.

The long-term safety of TCSs has not been confirmed by long-term follow-up studies.⁴³ Therefore, the continuous use of higher-potency products with higher risks for systemic side effects should be avoided, particularly in children. Cutaneous side effects and skin atrophy should be monitored for with regular physical examinations both in children and adults.^14,15,17-20

Statement 12: Secondary infections of AD should be treated with short-term topical or systemic antibiotic or antiviral therapy as per causative agent; antibiotics should not be used long term.

Secondary infections are a common problem in patients with AD and may warrant short-term topical or systemic antibiotic treatment.^15,20 This is particularly important since bacterial infections can flare AD. However, they should be used only for short periods and not long term to avoid antibiotic resistance.^15,20 Cultures should be performed to confirm the bacterial infection. For patients with repeat infections, bleach baths provide another effective therapy to control infection, using one-half cup of 5% household bleach per full bath (or 1 mL/L) two times a week.²⁰

Statement 13: Panel allergy testing and dietary modification are not routinely recommended for mild-to-moderate AD.

There is a perception that most patients with AD have food allergies. While atopic patients have more allergies than the rest of the population, the majority of mild/moderate AD patients do not.

Patient history should be used to guide the determination of what role, if any, specific food and environmental allergens play in the patient’s AD. For example, some patients’ eczema may be worse in the spring and fall when pollen is around or there are abrupt changes in temperature, or react shortly after eating certain foods, which may indicate a significant allergen. Patients should be assessed by an allergist for confirmation of an alleged food allergy and employ restricted diets or food avoidance only after allergies have been confirmed, according to established National Institute of Allergy and Infectious Disease guidelines.⁴⁴ Currently, there is no evidence that milk- or egg-free elimination diets or food-restricted diets benefit patients with AD.¹⁵

Statement 14: Many patients with AD have difficulty adhering to management recommendations, leading to poorer outcomes.

Patient outcomes and clinical improvement are closely related to topical medication adherence and are especially important in chronic dermatological diseases such as AD. Providers can help increase adherence with the selection of the correct medication, the involvement of family members or friends in the patient’s treatment plan, the use of simple and clear written treatment plans, by explaining likely side effects to the patient prior to use of the medication, and through frequent, ongoing follow-up clinic visits.⁴⁵ Table 2 lists key elements providers should strive to provide in their patient interactions that improve patient adherence to prescribed therapy.²⁵

Table 2.

10 Steps to Improve Patient Compliance.

1	Look patients in the eye; first impressions count.
2	Allow patients to verbalize their story.
3	Show you are interested and prepared to listen.
4	Touch and feel their skin.
5	Explain the condition and the rationale for treatment.
6	Solicit input and questions.
7	Demonstrate the application process.
8	Keep the treatment regimen simple.
9	Give patients contact information.
10	Provide instruction sheets for later home reference and education.

Provided by Feldman SR, Horn EJ, Balkrishnan R, et al. Psoriasis: improving adherence to topical therapy. J Am Acad Dermatol. 2008;59(6):1009-1016. doi:10.1016/j.jaad.2008.08.028.⁴⁵

Statement 15: New therapies based on a better knowledge of the pathogenesis of AD may lead to improved outcomes.

There remain an opportunity and a need to improve AD treatment with new approaches that treat the underlying disease and prevent the onset of new lesions by affecting pathogenic mechanisms. Recently 3 new, nonsteroidal, barrier creams (Atopiclair, Mimyx, and Epiceram) have entered the marketplace and have been shown to improve AD by repairing damaged skin barrier and providing some anti-inflammatory activity.⁴⁶ In addition, for moderate patients, newer agents that target immune responses and inhibit T cells and target T helper cells (Th)1, Th2, Th22, phosphodiesterase-4 (PDE4), IL-4 and IL-31, such as pascolizumab, REGN668, and crisaborole, show promise for the treatment of AD and are being evaluated.⁴⁷

Crisaborole ointment, a novel anti-inflammatory inhibitor of PDE4, has been shown to establish early sustained control of mild-to-moderate AD in patients aged ≥ 2 years in two 28-day, short-term, multicenter, phase 3 trials in which topical 2% crisaborole therapy reduced AD severity and pruritus severity, and improved other signs of AD (erythema, exudation, excoriation, induration/papulation, and lichenification) when compared with vehicle.⁴⁸ The favorable safety profile observed with crisaborole over the longer term in a multicenter, extension study (up to 52 weeks) suggests PDE4 agents such as crisaborole have the potential to effectively treat AD over the longer term without safety concerns.⁴⁹

Discussion

Inconsistencies and differences among guidelines were acknowledged and addressed given they can have a negative impact on implementation and adherence and result in inconsistent, suboptimal patient care. It is hoped that this update and review of guidelines coupled with the expert opinion and clinical experience of the panel will help standardize and guide topical AD care. Recommendations contained in this paper aim to assist primary care physicians, allergists, pediatricians, and dermatologists in their treatment of mild-to-moderate AD and address clinical challenges and inconsistencies in treatment.

Limitations

Statements used in the position paper were based on a mix of data and expert opinion. While it is possible that alternatives for AD treatment guidelines could exist, the statements are suggestions for best practice developed from a panel of expert clinicians that are supported by peer-reviewed literature and other existing guidelines.

Conclusions

The treatment of AD should involve a multitherapeutic approach that incorporates management of acute flares and preventive strategies to prolong the time between flares. Clear, simple treatment plans, agreed on jointly between the health care provider and patient and close, frequent follow-up provide means to improve the poor adherence associated with chronic topical therapies. Patient preferences, and cost of moisturizers and topical anti-inflammatories, should both be considered when developing a treatment plan, and plans should be adjusted and changed according to patient safety, effectiveness, and compliance.

DERMA AD Algorithm for Topical Treatment and Maintenance of Mild-to-Moderate AD

The DERMA (D: Diagnosis/Distribution; E: Education/Emollients; R: Red/Itchy; M: Medication/Maintenance; A: Assessment /Adherence) AD Algorithm was developed for health care professionals treating patients with AD. The algorithm is targeted to a wide base of health care professionals such as nurses, general practitioners, pediatricians, pediatric dermatologists, and dermatologists.

The DERMA AD Algorithm (Figure 3) gives recommendations based on the consensus statements discussed in this paper using a nominal group technique and a Delphi approach.¹¹

The easy-to-apply algorithm aims to optimize topical treatment and maintenance therapy for patients with mild-to-moderate AD of all ages. To ensure accuracy, outcome reproducibility and the user-friendly nature of the algorithm, we used criteria (eg, the acronyms “SCRAP” and “RECUR,” as described by one of the authors [LG]) to analyze the algorithm. SCRAP: Simple (no unnecessary steps), Complete (must contain inputs/outputs), Right/correct (product correct results), Abstraction (major steps to details), Precise (unambiguous); and RECUR: R: Reliable (same outcome each time); E: Efficient (no extra steps); C: Clear instructions/Logical; U: Understandable (make sense); R: Remember (easy).

The algorithm is designed to follow treatment steps for every patient throughout his or her journey emphasizing education and moisturizer use as integral parts of treatment and maintenance of AD at every stage. As well it is important throughout treatment to address initial evaluation and adherence to treatment and undertake evaluation and reevaluation of the patient’s condition and tolerance to treatment. Table 2 describes 10 steps to improve patient adherence.⁴⁵ Assessment is ideally scheduled within 8 weeks to determine whether adequate progress is being made and to address confounding factors.

The algorithm is presented both in a paper and digital version.

Additional information for the DERMA Atopic Dermatitis Algorithm paper version is as follows:

Differential Diagnosis

Steps in the diagnosis are described in the text following statement 1 and include a detailed patient history with particular attention to other atopic diseases, family history of atopy, frequency, and severity of flares and triggers.²³ Complete physical examination of the patient’s skin is required to determine the extent of involvement as well as the severity of AD.^13,20,23-25

AD Diagnosis

Diagnostic procedures are usually not needed; however, patch testing may be considered to rule out allergic contact dermatitis, and cultures or scrapings may be necessary to rule out infection.¹³

Elements of the diagnosis include age, location, extent, and severity of affected skin, face/fold involvement. Itch, sleep disturbances, and effect on QoL should be taken into account when determining treatment. Adherence should be continuously reassessed, especially when there is lack of improvement with treatment. In addition, misdiagnosis should also be considered.

Education

Education is a crucial aspect of AD management and cannot be overemphasized. Patient education should cover all aspects of eczema management, including routine skin care, bathing, and trigger avoidance. Patients may also be educated about the skin barrier changes in AD and the rationale for therapy. Appropriate expectations and goals for management can be discussed.

Triggers of AD

Triggers of AD should be avoided when possible. Such triggers may include irritants, contact allergens, and aeroallergens.¹³

Bathing

The frequency of bathing is controversial; short-duration lukewarm baths are often recommended for patients with AD as part of standard care and should be immediately followed by adequate application of a moisturizer to damp skin.^14-17,20 Nonsoap mild cleansers with a low or neutral pH (5.4-5.9) and those that are fragrance free should be used sparingly to “dirty” areas (ie, genitals, axillae, other folds). For patients with recurrent skin infections or those patients for whom Staphyloccocus aureus is thought to play a role, diluted bleach baths (using one-half cup sodium hypochlorite per full bath or 1 mL/L) twice weekly may be recommended.^15,31

Moisturizer Use

Moisturizer use is the cornerstone of skin care for all patients with AD. Moisturizers should be continued both in periods of remission and during flares when they are used in conjunction with medications.^14-20,23

Instructions for Use Per Severity

Mild AD or face and folds: Consider low-potency TCSs or TCIs or PDE4s for patients older than age 2 years. Even for mild AD on the trunk and extremities, mid-potency TCS could be considered.

Moderate AD: Consider a mid-potency TCS or TCI or PDE4. If the patient does not improve after 4 weeks of adherent therapy, consider a different class of medication. If the skin clears but then flares quickly, then consider initiation of maintenance therapy with a TCS or TCI twice per week.

If the patient does not clear after 4 weeks, then reassess adherence, reassess AD severity, and ensure that the diagnosis is correct. Further information can be found on the Eczema Society of Canada website and the Canadian Pediatric Society websites: https://eczemahelp.ca/eczema-treatment/ and www.caringforkids.cps.ca.

TCS Classes

TCSs are available in various strengths from low, mid to potent, and very potent.²⁰ Low-potency TCS products are considered appropriate for face and folds and for the very young, while high-potency TCSs are generally used for lesions that are very chronic and lichenified.

TCIs

Other recommended topical anti-inflammatories are TCIs. These are applied to involved skin twice a day until the skin is clear or almost clear.^{14-17,23,38,39} TCIs are approved in Canada for age ≥ 2 years.

Once the skin is clear, reduce frequency of application of TCI to twice a week as maintenance, still using moisturizers twice a day. If skin remains clear, stop the TCI and continue the moisturizer. If there are frequent flares, keep the patient on a maintenance treatment with TCI for twice a week.

PDE4s

Crisaborole ointment is an anti-inflammatory inhibitor of PDE4 for mild-to-moderate AD in patients age ≥ 2 years.⁴⁹ The ointment can be used twice daily until the skin is clear or almost clear.

Frequent Flares

If the patient continues to experience frequent flares despite ongoing daily moisturizer, consider continuing TCS/TCI, or PDE4 to affected areas once or twice per week as maintenance therapy, although maintenance with PDE4 has not yet been studied. If the flares are infrequent, then the patient can use a moisturizer and routine skin care daily and resume medicated therapy only for subsequent flares.

Facial Mild-to-Moderate AD

Higher-potency TCSs may cause thinning on facial skin and is generally avoided. Low-potency TCSs are suitable for facial AD and TCIs or PDE4s can be utilized in this location as TCS-sparing agents. If this doesn’t work, consider AD as severe and refer to a specialist.

Footnotes

Acknowledgements

The authors acknowledge and thank Anita Simon and Anneke Andriessen, PhD, for their invaluable assistance with preparing this manuscript.

Declaration of Conflicting Interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:

Charles W. Lynde has been a consultant, principal investigator, and speaker for Celgene, Galderma, Genzyme, GSK, Johnson & Johnson, LeoPharma, Novartis, Pfizer, Sanofi Aventis, and Valeant.

James Bergman has been a consultant for Aralez, Cipher, Dermtek, Galderma, GlaxoSmithKline, Janssen, Johnson & Johnson, La Roche Posay, Leo, Mead Johnson, Mustela, Nestle, Novartis, Pediapharm, Pierre Fabre, Pfizer, and Valeant; and a speaker for Aralez, Cipher, Johnson & Johnson, Nestle, PediaPharm, Pierre Fabre, and Valeant.

Loretta Fiorillo has been a consultant for Amgen, Abbvie, Celgene, Galderma, Johnson & Johnson, Leo Pharma, Pfizer, and Valeant; an investigator for Celgene; and a speaker for Astellas, Celgene, Pedia Pharma, and Novartis.

Lyn Guenther has been a consultant for Celgene, Galderma, GSK, Johnson & Johnson, Leo Pharma, Pfizer, Sanofi Aventis, and Valeant; an investigator for Celgene, GSK, Leo Pharma, Novartis, and Roche; a speaker for Astellas, Celgene, GSK, Leo Pharma, Novartis, Pfizer, Sanofi Aventis, and Valeant; and has given expert testimony for Leo Pharma.

Jill Keddy-Grant has been a clinical investigator for Abbvie, Amgen, Astellas, Celgene, Galderma, Regeneron, and Leo Pharma; and has served on advisory boards for Abbvie, Actelion, Aralez, Bayer, Celgene, Cipher, Janssen, Leo Pharma, Mustela, Pierre Fabre, and Valeant.

Ian Landells has been an investigator for Abbvie, Janssen/J&J, Amgen/Pfizer, Merck, Valeant, BMS, Celegene, Galderma, Allergan, Leo, Basilea, Novartis, Astellas; a speaker for Abbvie, Janssen/J&J, Amgen/Pfizer, Merck, Valeant, Astellas, Pediapharm, Leo, Novartis, GSK, and Lilly; and an advisor for Abbott, Janssen/J&J, Amgen/Pfizer, Celegene, Cipher, GSK, Novartis, Allergan, Lilly, and Valeant.

Danielle Marcoux has been a consultant for Abbvie, Celgene, Galderma, GSK, Johnson & Johnson, Leo Pharma, Pfizer, Sanofi-Regeneron, and Valeant; an investigator for Abbvie, Celgene, Galderma, Leo Pharma, Lilly, and Novartis; and a speaker for Fondation Dermatite Atopique, Pfizer, Sanofi, Leo Pharma, Johnson & Johnson, and Valeant.

Michele Ramien has been a consultant for Actelion, Amgen, Abbvie, Cipher, Johnson & Johnson, Leo Pharma, Novartis, Pierre Fabre, Pfizer, and Valeant.

Wingfield Rehmus has been a consultant for Abbvie, Cipher, Mustela, Pfizer, Pierre Fabre, and Valeant; and a speaker for Abbvie and Valeant.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by unrestricted educational grant from Pfizer.

ORCID iDs

Jill Keddy-Grant

Michele Ramien

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