¹Hospital for Sick Children, Toronto, ON, Canada
²University of Calgary, Calgary, AB, Canada
³University of British Columbia, Vancouver, BC, Canada
⁴Toronto Western Hospital, University Health Network, Toronto, ON, Canada and Department of Dermatology, Brown University, Providence, RI, USA
⁵University Health Network, Toronto, ON, Canada
⁶Centre hospitalier universitaire Sainte-Justine, Montreal, QC, Canada
⁷British Columbia Children’s Hospital, Vancouver, BC, Canada
⁸Eczema Society of Canada / Société canadienne de l’eczéma, Keswick, ON, Canada

This manuscript was previously disseminated by Eczema Society of Canada Copyright© by the Eczema Society of Canada / Société canadienne de l’eczéma July 2016; revised 2017. All rights reserved. Third Edition

About Atopic Dermatitis

Eczema (atopic dermatitis), is a chronic, pruritic inflammatory skin condition that follows a relapsing course affecting people of all ages, although it is more frequent in children. Eczema is most often diagnosed and managed by primary care providers. This article aims to provide practical guidance to primary healthcare practitioners who care for patients with eczema. The Eczema Society of Canada/Société canadienne de l’eczéma convened a group of Canadian dermatologists with extensive experience in managing paediatric and adult patients with atopic dermatitis, to develop practical recommendations for the management of atopic dermatitis. They developed clinical recommendations based on expert consensus opinion and the best available medical evidence. The experts developed recommendations that focus on three key areas of managing patients with eczema: (1) patient/caregiver education, (2) addressing skin barrier dysfunction and (3) inflammation control. Therapeutic education directed to the patient or main caregiver(s) has been demonstrated to improve QoL.¹ While complete guidelines on AD are available,^2-5 these guidelines may not be practical for everyday clinical practice in primary care, nor are they specific to the Canadian healthcare system.

Abbreviations: AD – Atopic Dermatitis, QoL – Quality of Life, SOA – Sedating Oral Antihistamine, TCI – Topical Calcineurin Inhibitors, TCS – Topical Corticosteroids

Background

• Atopic dermatitis (AD)-also commonly referred to as eczema or atopic eczema-is a chronic, pruritic, relapsing inflammatory skin condition that impacts quality of life (QoL) and places a significant burden on patients and families.
• It can affect people of all ages but it is more frequent in children.
• Eczema is characterized by periods of acute worsening symptoms, known as flares, alternating with periods of symptom remission, but some patients do not have any remission.
• Patients often have associated atopic disorders, such as allergic rhinoconjuncitivitis, food allergies and/or asthma.
• The onset of eczema is typically between 2 and 6 months of age, although it can begin at any age. It was previously thought that eczema resolved or improved by adulthood in most cases, but evidence suggests that it is a chronic condition that may persist into adulthood.^6-8
• Eczema is caused by a dysfunctional skin barrier and dysregulation of the immune system, due to genetic, immunologic, and environmental factors. Pruritus is the most notable feature of eczema, which is at the centre of much of the disease burden for patients and their families.

Diagnosis & Assessment

• Eczema is most often diagnosed and managed by primary care providers.⁹
• Eczema is diagnosed based on the morphology and distribution of the patient’s skin lesions, associated clinical signs, and family history (Table 1).¹⁰ Eczema can range from mild to severe, based on body surface area involvement, extent of eczematous lesions, and the impact on a patient’s QoL.
• At this time, eczema remains a clinical diagnosis. In select cases additional testing may be performed, such as a biopsy or patch testing, to rule out other conditions, but this is usually unnecessary. If the diagnosis is unclear, referral to a dermatologist should be considered.

Quality of Life in Eczema Assessment

• Eczema has a significant impact on QoL for patients and their families. Physicians should consider addressing this impact on QoL with their patients and patients’ families, in addition to assessing the signs and symptoms of the disease.
• Sleep is disturbed, often for the whole family. Healthcare providers should address itch, sleep loss, and disease impact on mood, activities, behaviour and self-esteem, when diagnosing eczema and formulating a management plan.
• The impact of AD on QoL for the patient and his or her family is often very significant. The level of impact has been found to be similar and at times can surpass the effect that diabetes has on the family.¹¹

Minimizing and Controlling Flares

• Eczema is a relapsing-remitting, chronic disease with cyclical periods of relative quiescence and periods of flares.
• Currently, there is no cure for eczema. As such, the main goal of eczema management is to improve baseline inflammation and xerosis and to reduce the frequency and severity of flares. For some patients, treating baseline disease activity will involve emollient use only. For others it will involve the use of emollients and topical anti-inflammatory medications to any inflamed areas. In periods of flare, treatment needs to be increased beyond this baseline.
• For those mild disease and mild flares, adding a topical anti-inflammatory medication to their emollient regimen may be necessary.
• For others with more severe eczema, a temporary increase in the potency of topical anti-inflammatory medications may be required.
• For patients with frequent flares and flares that require high-potency topical corticosteroids, referral to a dermatologist is recommended.

Patient Education

• Suboptimal treatment and poor adherence to therapy are common in patients with eczema, much like in patients with other chronic diseases that require regular intervention. Therefore, therapeutic education is particularly important in the face of many sources of potentially misleading or inaccurate information, or patient misconceptions and fears present in the community.¹²
• Patient and caregiver education is a key aspect of successful eczema management.¹³ Studies have demonstrated that therapeutic patient education increases adherence to therapy, increases the use of moisturizers, and decreases fear of medications.^14-16

Patient counselling should focus on the following key points:

• Eczema is a chronic disease. There is no cure, but control of the disease can be achieved. Eczema typically goes through periods of flares and remissions. Moisturizing is the mainstay of therapy during remission, and prescription treatments are needed for any areas of inflammation.
• Eczema flares can be managed by hydrating the skin (bathing and moisturizing appropriately) and reducing inflammation with topical medication.
• Undertreating, starting treatment too late, or stopping treatment too soon, should be avoided. Treatment of eczema flares should begin at the first sign of inflammation. Patients and caregivers often stop treatment before the skin is fully clear of lesions, mistakenly believing that the vast improvement they have seen means the skin is “clear enough.”
• Clinicians should encourage patients and caregivers to make sure the skin is completely clear of lesions before stopping treatment, since even though eczema flares may seem to be much less severe, the patient still has chronic active inflammation, and often the skin rapidly becomes worse.
• Patients need to be counselled on how to apply the medication, as applying the treatment sparingly may contribute to under treatment.
• Adherence to therapy is essential for the optimal management of eczema. Poor adherence may be the most significant barrier to optimal care in eczema. In a survey of 200 eczema outpatients, 24% admitted that they did not adhere to treatment, and experts estimate this percentage could be significantly higher.⁵ Healthcare providers should counsel patients and caregivers about the importance of adhering to treatment.
• Trigger avoidance:
  • Patients should be counselled to attempt to identify and avoid their triggers, and to understand that some eczema flares occur despite strict trigger avoidance and diligent skin care. This is often a source of frustration for patients.
  • Many eczema flares do result from some environmental trigger. Common triggers include harsh or fragranced soaps and self-care products, rough fabrics, overheating and sweating, and winter weather. Often these triggers can be identified but not avoided, such as weather changes.
  • Lifestyle can impact eczema as well, such as sweating for a young athlete. Instead of advising the patient to avoid pleasurable activities, help the patient learn about ways to manage the eczema flare that may follow an activity or exposure to an eczema trigger.
  • Additional actions can be taken to help the condition, such as keeping nails trimmed short and filed smooth to help reduce damage done by scratching.
  • Distraction can also be helpful during episodes of acute itch, particularly activities that keep the hands busy.
• Patients and caregivers often seek causes or cures for eczema, which diverts attention away from the treatment plan. Patients should be counselled on the chronicity of atopic dermatitis, and reminded that broad panel allergy testing and restrictive diets are not recommended in the absence of signs and symptoms consistent with an IgE-mediated allergy.
• For additional patient support, information and education, recommend reliable sources, such as the Eczema Society of Canada/ Société canadienne de l’eczéma, Canadian Dermatology Association, American Academy of Dermatology, National Eczema Association (USA), or National Eczema Society (UK)

Written Eczema Care Plans

• A written eczema care plan is a recommended tool to improve therapeutic outcomes.^{17, 18} Patients and caregivers may benefit from having a written plan in order to carry out the multi-step plan of caring for eczema, which often includes specific bathing and moisturizing recommendations and instructions for using prescription medications (type and dosage). For a sample written eczema care plan, see Figure 1.

Skin Care

Moisturizers

• Frequent application of moisturizers is the cornerstone of eczema management,¹⁹ helping to decrease itch, preventing and reducing flares, and decreasing the need for prescription medications.
• Xerosis results from skin barrier dysfunction and is present to some degree in most patients with eczema. Moisturizers are used to reduce xerosis, which reduces itching, and they also reduce transepidermal water loss.²⁰
• For patients with mild eczema, frequent and consistent use of moisturizers may sufficiently manage the disease. In moderate to severe disease, moisturizing is still a fundamental part of treatment. Patients may need to be explicitly counselled on how to use moisturizers in conjunction with other topical prescription treatments.
• Patients should select moisturizers that are soothing and do not irritate the skin. Ideal moisturizers contain varying amounts of emollient, occlusive and humectant ingredients. While thicker products that both moisturize and provide a barrier are recommended, there are many moisturizers to choose from and patient preference is important.
• The consistent use of a moisturizer that is well-tolerated by a patient is more important than the specific product selected.
• There is insufficient evidence to recommend a specific optimal regimen for use of moisturizers. However, this consensus group suggests that generous application, one to several times a day, is necessary to help minimize skin dryness. It is highly recommended to apply moisturizers immediately after bathing or any water exposure to improve skin hydration.^{21, 22}

Barrier Repair & Barrier Repair Products

• Patients with atopic dermatitis have impaired skin barrier function, partly due to deficiencies in ceramides (lipids) and filaggrin (a protein), components of the outer skin barrier. These deficiencies contribute to a degraded skin barrier that allows bacteria, irritants, and allergens to enter the skin, and also allows moisture to escape.²³ To address this, ceramides are increasingly available in over-the-counter moisturizers, as well as one prescription barrier repair treatment.

Bathing & Showering

• Daily bathing is often recommended for patients with eczema; however, there is no evidence to support a standard recommendation for the frequency, duration or the method of bathing. Moisturizing after bathing is strongly recommended.^{21, 22}
• Clinicians can recommend that patients bathe or shower (5-10 minutes) in warm, plain water once daily, or every other day, based on patient preference (e.g., baths may sting open eczema lesions making daily bathing challenging).
• Gentle cleansers may be used only on areas that need cleaning, and should be used at the end of the bath or shower. Bathing using this method should not aggravate eczema.
• Moisturizing should immediately follow bathing or showering, since exposure to water can exacerbate eczema if the skin is not moisturized soon after exiting the water.
• Evidence is lacking to support the use of bath additives such as oils, emollients, bath salts, and most other products.

Inflammation Control

Topical Corticosteroids

• Appropriate use of topical corticosteroids (TCS) is a safe and effective first-line therapy in the treatment of the inflammatory component of eczema.²⁴
• Consider factors such as the age of the patient, areas of the body to be treated, xerosis, and patient preference when prescribing appropriate topical corticosteroids.
• Selecting the appropriate agent, including the appropriate strength, can be challenging. In general, low potency TCS (classes VI and VII) are recommended for the face, neck, skin folds, and groin, for both paediatric and adult patients.
• Moderately potent medications (classes III, IV, and V) are recommended for the trunk and extremities. Higher potency TCS may be required for refractory eczema or lichenified areas.
• Consider referral to a dermatologist in these cases.
• Once to twice daily application of TCS are the generally recommended treatment during an acute eczema flare.
• Treatment should be stopped once the affected areas are smooth to the touch and no longer itchy or red.
• If no response to treatment is seen after 1 to 2 weeks, re-evaluate to consider other diagnoses or treatment plans. With appropriate use, the incidence of adverse events is minimal.²⁵
• When prescribing combination treatments, TCS strength should be taken into consideration, as the TCS could be of higher potency than is appropriate.
• Patients and caregivers may fear the side effects of pharmacological treatments. Fear of topical corticosteroids is common and should be recognized and addressed. This may be particularly important for paediatric patients.
• Addressing fears and concerns may help improve adherence and avoid under-treatment or non-treatment.
• Patients who are using corticosteroids over the long term should be monitored, and should have regular physical examinations to watch for cutaneous side effects. Monitoring of eczema patients for systemic side effects from topical corticosteroids is not routinely recommended.^{26, 27}
• In patients who have good adherence to their treatment plan and experience periods of remission, but flare frequently in predictable areas, maintenance treatment with topical corticosteroids may be suitable. Intermittent application (one application 1 to 2 times a week) of a moderately potent topical corticosteroid is recommended for proactive treatment on areas that are commonly at risk of flare.²⁸

Topical Corticosteroid Side Effects

• As with all medications, TCS can have side effects (Table 2). However, when they are used appropriately, the incidence of side effects is low, and patients should be counselled accordingly.²⁹
• The burden of under- and untreated eczema usually outweighs the risks associated with TCS.³⁰

Topical Calcineurin Inhibitors

• Topical calcineurin inhibitors (TCI) (i.e. tacrolimus and pimecrolimus) are a class of anti-inflammatory medications that are a recommended safe and effective second-line therapy option for treatment of acute flares of eczema.³¹
• Whereas TCS are generally considered first-line topical treatment for eczema, TCI can also be used off-label as first-line therapy in select cases, particularly for areas that are sensitive to the adverse effects of TCS, such as the eyelids.
• TCI are also appropriate second-line therapy for eczema that does not respond to TCS or in patients intolerant of TCS.
• TCI can also be used as a preventive therapy, 2 to 3 times a week in areas of predictable flares similar to the preventative strategy described for TCS above.³²
• Proactive, intermittent use of TCI has been shown to be more effective than the use of emollients alone.^{33, 34}

Topical Calcineurin Inhibitor Side Effects

• Mild to moderate burning or stinging sensation of the skin can occur with TCI use, and patients and caregivers should be counselled about this possible reaction.
• Patients who use tacrolimus may have flushing of the face when they consume alcohol.
• Based on concerns about an increased risk of cancer with the use of TCI use, the US Food and Drug Administration (FDA) issued a black-box warning shortly after the class of medications came on to the market. Shortly after the FDA warning was issued, Health Canada issued a similar warning. However, TCI have been available for over 15 years and recently published data does not support those concerns.^35-39 Healthcare providers should be aware of the black-box warning and discuss it with patients.

Adjunctive Therapies

Antimicrobials

• Skin infections can worsen eczema and should be addressed when present.
• Clinical signs of infected eczema include crusting, oozing, and pus.
• Gram-positive bacteria, in particular Staphylococcus aureus, is frequently found on the skin in eczema.⁴⁰
• Mild infection may be treated with a topical antibiotic adjunctively with a topical anti-inflammatory agent.
• The routine use of topical antistaphylococcal antibiotic treatment in the absence of clinical signs of infection is not recommended.⁴¹
• When clinical signs of bacterial infection are seen, swabs for culture and sensitivity should be considered, partly because of the increased prevalence of resistant organisms, and empiric oral antibiotics targeting streptococcal and staphylococcal infections can be started.
• In patients who frequently show clinical signs of secondary bacterial infection, consider bleach baths as prophylactic therapy.⁴²

Bleach Baths

• In patients where infections are common, bleach baths can be done once to twice per week, and consist of bathing in a dilute solution of bleach and clear warm water.⁴³
• Patients and/or caregivers can create a dilute bleach bath at home by adding 120 mL (1/2 a cup) of regular strength household bleach (6% sodium hypochlorite) to a full standard-size bathtub of warm water (which is usually about 150 litres). This concentration of bleach is quite low (0.005%).
• For smaller bathtubs, patients may use 1 teaspoon (5 mL) of regular bleach for every 5 litres of water.⁴²
• The bleach and clear water should be mixed well, and the patient should bathe in the solution for 5 to 10 minutes, thoroughly rinsing the skin after with warm clear water.
• Rinsing should be immediately followed by application of prescription treatments, if needed, and moisturizers.
• Patients and caregivers should be explicitly counselled on how to perform the bleach bath, including how to select the correct concentration of bleach and safe dilution practices.

Managing Viral Infections

• Viral infection with herpes simplex virus can cause eczema herpeticum, a potentially life-threatening condition.
• Swabs for viral detection (such as viral culture, or polymerase chain reaction) should be performed in suspected cases of eczema herpeticum, in addition to initiation of treatment with an appropriate antiviral agent.⁴⁴
• Eczema coxsackium is a form of hand-foot-and-mouth disease in patients with eczema that is more extensive than routine hand-foot-and-mouth disease, and can look similar to eczema herpeticum.
• Molluscum contagiosum occurs more commonly in eczema patients and the presence of the virus can lead to eczema surrounding the mollusca, potentially exacerbating an eczema flare.

Antihistamines

• Due to a lack of evidence of their efficacy in patients with eczema, non-sedating oral antihistamines are not recommended for use.⁴⁵
• Sedating oral antihistamines (SOA), such as hydroxyzine and diphenhydramine, can be used in patients whose disease significantly interferes with sleep.
• It should be noted that long-term use of SOA may lead to a reduction in the efficacy and sedative effects of the treatment.⁴⁶
• Control of inflammation and itch, through the use of previously discussed prescription anti-inflammatory medications and appropriate bathing and moisturizing may mitigate the need for sedating antihistamines in many patients.
• Patient reliance upon regular antihistamine use should be an indication that the treatment plan is not optimally managing the condition.⁴⁷

Allergy Testing & Restrictive Diets

• The relationship between eczema and allergy is complex. While children with eczema have a significantly higher incidence of food allergies, food does not cause eczema flares for most patients.
• In an AD patient who has confirmed food allergies, exposure to the allergenic foods can induce urticaria, which can indirectly worsen the eczema.
• If a patient shows true allergic signs and symptoms such as urticaria or anaphylaxis to a food, that food should be avoided and an epinephrine auto injector should be prescribed, until an allergist/immunologist can be consulted.
• Routine allergy testing with eczema as the only symptom is not currently recommended.
• Broad spectrum panel testing for a variety of foods is not recommended, as it often leads to a number of false positive results.⁴⁸
• Food elimination diets or restrictive diets are not recommended as an eczema intervention.
• Excessive, prolonged food elimination diets, especially in children, may lead to weight loss, poor growth, and nutritional deficiency.⁴⁹

Supplements & Alternative Therapies

• There is limited evidence to support the routine use of dietary supplements and alternative medicines for the treatment of eczema. However, some patients may find dietary supplements or alternative interventions to be helpful.
• If the dietary supplements or interventions are not harmful, the patient should be counselled and supported accordingly. However, if these interventions could be harmful, patients should be counselled and cautioned.
• Extra caution should be taken in the case of infants and children.

Refractory and Severe Eczema

• Phototherapy⁵⁰ and/or systemic immunomodulatory agents may be necessary for refractory and severe eczema, and they should be used by health care providers versed in their use.⁵¹
• Phototherapy, specifically broad- and narrow-band UVB, can be used for pediatric and adult patients with AD. It is a safe and effective treatment for most patients, but a major barrier to its use is accessibility as it requires visits to a physician’s office multiple times per week. Furthermore, long term side effects, such as skin cancer, have not been well-established in the paediatric population.
• Cyclosporine, methotrexate, azathioprine and mycophenolate mofetil are the systemic agents commonly used for atopic dermatitis. All of these agents may cause significant adverse events and require regular monitoring, so they should be used with caution and after appropriate discussion of their risks and benefits with patients and their families. Specific guidelines for their use, including dosing schedules and adverse effects, are beyond the scope of this review.
• Referral to a dermatologist should be considered in patients with refractory eczema in whom systemic therapy is being contemplated.

Systemic Corticosteroids

• Systemic corticosteroids, such as prednisone, are not recommended for the routine management of atopic dermatitis.
• While systemic corticosteroids can rapidly ameliorate the signs and symptoms of an acute eczema flare, patients often have a disease flare upon withdrawal of the corticosteroid.
• Given the long-term consequences of chronic systemic corticosteroid use, they should be avoided whenever possible in patients with atopic dermatitis.⁵²

M. Weinstein, MD, FRCPC (Pediatrics), FRCPC (Dermatology)

Assistant Professor of Pediatrics and Medicine, University of Toronto, Toronto, ON, Canada
Staff Dermatologist, Division of Pediatric Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada

Background

Atopic dermatitis (AD) or eczema is a chronic, relapsing skin condition that can lead to xerosis, pruritus, and patches of dermatitis. Coping with the physical and emotional aspects of AD can significantly impact the quality of life. It is most common in childhood, as many patients seem to outgrow the condition by adulthood. The etiology of AD is complex and not fully understood, but contributing factors include a dysfunctional skin barrier that allows moisture to escape and irritants to enter, as well as inflammatory mediators. There is increasing interest in exploring the feasability and efficacy of using non-drug alternatives as adjuncts to conventional pharmacologic approaches. Lifestyle modifications that can aid AD management will also be reviewed.

Diagnostic Features

• Chronic or chronically relapsing dermatitis
• Typical morphology and distribution (e.g., flexural erythema, excoriations, lichenification, xerosis)
  • Facial and extensor involvement in infants and children; flexural dermatitis and lichenification in adults
• Early age of onset – AD affects up to 20% of children¹
• Intensive itching that can cause disruptive sleep or difficulties in concentration
  • Breaks in the skin from scratching can lead to secondary infection
• Personal or family history of atopy (i.e., asthma, allergic rhinitis, AD)
• Hyperreactivity to environmental triggers

Defects in the Skin Barrier

There is growing data to support the longstanding theory that AD may be caused by a genetic defect in the epidermis, permitting environmental irritants, microbes, and allergens to penetrate, which in turn elicit inflammatory responses.²

• The filaggrin gene contributes to the formation and function of the skin.
• Deviations in the gene coding for filaggrin can cause skin barrier defects that contribute to AD.
• Defects in skin barrier development prevent adequate levels of antimicrobial peptides to form in the epidermis. Consequently, bacterial and viral infections may occur in affected lesions.

Treatment Options

• Avoidance of triggers
• Emollients/moisturizers
  • Standard adjunct for prevention and maintenance
• Topical corticosteroids
  • The cornerstone of AD therapy
  • Potential for tachyphylaxis, skin atrophy, and systemic side-effects, especially in long-term use
• Topical calcineurin inhibitors (TCIs)
  • Useful when conventional therapies fail or are unsuitable
  • In 2006, an FDA boxed warning was issued for TCIs over concerns of immunosuppression and the potential risk of malignancy following long-term or continuous use
• Antimicrobials for infection
  • Topical or oral antibiotics may be prescribed to treat infected lesions
  • Overuse or prolonged treatment increase the risk for developing antibiotic resistance
  • Oral antivirals can be used for cases of eczema herpeticum (eczema infected with herpes virus)
• Oral antihistamines for pruritus
  • Often tried for intractable itch, but little evidence exists to support their antipruritic effect
• Systemic corticosteroids, systemic immunosuppressants and phototherapy
  • Reserved for severe disease

Moisturizing and Bathing

Moisturizers

• Daily moisturization is essential for managing AD, both during and between flare-ups.
• A randomized controlled study demonstrated that moisturizers can improve the barrier function of skin; however, the effects are determined by individual product composition.³
• Basic essential components of moisturizers include emollients and humectants.
  • Emollients provide a protective film by filling-in spaces between cells and restoring lost lipids to prevent transepidermal water loss (TEWL).
    • Commonly used emollients include animal oils, butyl stearate, cocoa butter, lanolin, lipids, mineral oil, petrolatum, and shea butter.
    • Petrolatum is the gold standard emollient; its non-sensitizing and highly occlusive properties are effective against TEWL.
    • Ceramides are lipid molecules that are important components of skin structure; they improve the skin barrier by limiting TEWL and preventing the entry of irritants.
    • AD patients have significantly fewer ceramides in their stratum corneum.
    • Lipids can be replaced topically with a ceramide-dominant emollient.
  • A new class of emollients, now available in the US, aims to replenish certain molecules that are deficient in the skin of AD patients. These nonsteroidal moisturizers are very expensive, but study findings indicate their efficacy and safety for mild to moderate AD.⁴
  • Humectants aid in the absorption and retention of moisture, and soften thickened skin.
    • Commonly used humectants include glycerin, hyaluronic acid, lactic acid, propylene glycol, panthenol, silicones, and urea.
    • Glycerin’s high affinity to attract moisture to the skin makes it the most widely used.
    • Panthenol (vitamin B5) functions as a humectant, emollient, and moisturizer. Studies examining adjuvant care with panthenol showed improved hydration and reduced dryness, itching, and inflammation.⁵

Choosing a Moisturizer

• Generally, the greasier the better. Bland ointments, such as petrolatum, are non-irritating and provide an excellent barrier, but they can be perceived by patients as being too thick.
• Less greasy creams and lotions may be more irritating.
• Some acids (e.g., salicylic acid and lactic acid) and humectants (e.g., urea) can be poorly tolerated by eczematous skin. Avoid their use in infants and small children due to the risk of systemic absorption.

Bathing

• Bathing first, and then applying a moisturizer while the skin is still damp, will help trap moisture in the skin. Medicated treatments should be applied to any dermatitis and moisturizers to unaffected skin.
• Bathing more than once daily is not always practical. Although, during flare-ups, several short baths followed by daytime applications of a moisturizer can be helpful.
• Baths (or showers) should be taken with warm (not hot) water and limited in duration.

Advancements in the Use of Natural Anti-inflammatories

Increasingly, patients prefer to supplement medical treatments with over-the-counter skin care products that incorporate natural ingredients. Plant-derived extracts are one of the largest categories of additives found in moisturizers. A few notable compounds have emerged following scientific evaluation, which supports their therapeutic benefits for alleviating symptoms associated with AD and other inflammatory skin conditions.⁶

Aloe Vera

• Applications include its use as an anti-inflammatory, analgesic, antipruritic, antioxidant, and wound healing agent.
• Chamomile (Matricaria recutita)
• Topical use can relieve skin irritation. The active components (á-bisabolol, á-bisabolol oxide A and B, matricin) inhibit enzymes that mediate inflammation and suppress histamine release.
• Its anti-inflammatory effect is approximately 60% of that elicited by hydrocortisone 0.25%.⁷

Colloidal Oatmeal

• It has multiple active components that include enzymes, flavonoids, lipids, proteins, polyphenols (avenanthramides), polysaccharides, and vitamins.
• Avenanthramides are potent phytochemicals that inhibit the release of proinflammatory cytokines, resulting in reduced contact hypersensitivity and inflammation.⁸
• It also has antioxidant, anti-irritant, antihistaminic, and immunomodulatory effects.
• Colloidal oatmeal is one of few natural ingredients approved as a skin protectant by the US FDA.

Feverfew (Tanacetum parthenium)

• Its broad spectrum of clinical applications is attributable to its potent anti-inflammatory, antioxidant and anti-irritant properties.
• Parthenolides are compounds in feverfew that can produce skin sensitivities. Development of a purified extract that is free of parthenolides has been shown to have strong anti-inflammatory activity through inhibition of proinflammatory cytokine release.⁹

Licorice Extracts (Glycyrrhiza glabra, Glycyrrhiza inflata)

• Glycyrrhiza glabra (contains glabridin) reduces irritation, inflammation, and melanin production.
• Glycyrrhiza inflata (contains licochalcone A) decreases irritation and inflammation.
• Twice daily application of a licochalcone A-containing lotion for 8 weeks by patients with mild to moderate red facial skin produced statistically significant improvements in erythema scores.¹⁰

Avoidance of Triggers

Avoidance of triggers is a key AD management strategy. Each patient and his or her physician need to identify and eliminate relevant triggers.

Food

• While AD patients are more prone to food allergies (type 1 hypersensitivity), it is unclear if certain foods can cause a flare-up, which is more of a type 4 hypersensitivity reaction.
• If there appears to be a food trigger, parents or patients should keep a diary to track foods eaten and flare-ups. Food elimination diets should be physician supervised.
• If type 1 allergic symptoms develop in response to a particular food, avoid ingestion until testing can be undertaken. If a food source is unclear, it may be useful to involve an allergist.

Aeroallergens

• Certain aeroallergens (e.g., dust mites or seasonal allergens) can trigger AD flares.^11,12
• Confirmatory testing may be useful in refractory
• patients. If results are positive, deploy dust mite prevention strategies (e.g., frequently laundering mattress covers and avoid stuffed toys, feather pillows, duvets, and carpets).

Humidity/Sweating

• Sweating can aggravate itching and humid conditions that increase perspiration can induce flares. Frequently cooling off, changing clothes, and adjusting activities in humid weather can help.
• Heat and sweating can promote nighttime scratching. Recommend one layer each of sleepwear and covering. The bedroom should also be kept cool (but not cold).

Low Humidity/Dry Weather

• Due to the dry weather, most patients have worse flares in the winter. Moisturizing several times per day is crucial. Use of a cool mist humidifier in the bedroom can be helpful.

Infection

• AD patients are commonly colonized with Staphylococcus aureus (S. aureus) and have problems with S. aureus killing mechanisms.¹³ This frequently presents as a worsening of AD that is not responsive to therapy. Infected areas can appear as wet, oozing, or crusted lesions that require topical or oral antibiotics.
• S. aureus may drive AD flares through superantigen mechanisms, even in the absence of an actual clinical infection.¹⁴ Therefore, patients who have frequent flare-ups may need strategies to reduce S. aureus colonization and inflammation.

Environmental Irritants

• AD patients can be especially sensitive to dry grass, perfumes or fragrances in skin care products, and certain fabrics (wool and synthetics).
• Wearing cotton clothing can be helpful. Some evidence suggests that specially treated silk or silver-coated fabrics may also be beneficial.^15,16

Chlorine

• Swimming can be a good sport for AD patients, because sweating is not a concern. However, to avoid irritation, they should rinse off thoroughly afterwards and apply a moisturizer.
• There is a lack of data to confirm if salt water or chlorinated pools are better for AD patients.

Top

Normal Routines

School

• Children with severe eczema may engage in school-avoidance behaviours that are caused by fatigue due to nocturnal pruritus, or anxiety from being teased. These issues must be addressed promptly to re-establish a normal school routine.

Sunscreen

Many sunscreen products contain irritating ingredients. If regular sunscreens are unsuitable, suggest using sensitive skin formulations or physical sunblocks (e.g., titanium dioxide or zinc oxide).
A comprehensive sun protection strategy combines regular sunscreen use, avoidance of peak sun exposure times, and wearing hats and protective clothing.

Sleep

• Sleep disturbance from pruritus can be a major problem for many patients and their families, particularly if parents sleep with their AD-afflicted child and help to scratch or restrain their child’s hand to prevent scratching.¹⁷ Both practices should be discouraged and may indicate a need to increase antipruritic therapy and the use of emollients.
• Poor sleep can lead to patient and/or parental difficulties in concentration, irritability, and fatigue.

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Additional Tips

• Keep nails short to minimize tissue damage from scratching.
• Keep moisturizing creams in the refrigerator, as the cold sensation is soothing to itchy skin.
• For topical medical therapy, ointments are usually better tolerated than creams or lotions.
• Ask families if sleep routines are satisfactory and if sleep is disturbed. Many families do not volunteer this information to physicians.
• Patients should be steered toward good sources of information (e.g., http://www.eczemahelp.ca).

Conclusion

Successful AD management is best undertaken with a step-wise approach that considers multiple factors including disease severity, therapeutic side-effects, patient preferences, itch intensity, and sleep quality. As well, psychosocial impacts from AD cannot be overlooked. The regimented use of moisturizers can improve the skin barrier and significantly reduce xerosis and itch. As such, it can serve as useful adjunctive care for maintenance and flares. The new research realm directed at the epidermal barrier and the important immune factors carries the hope that innovative therapeutic approaches will lead to reduced infections and improved management of AD patients.

References

1. Williams H, et al. J Allergy Clin Immunol 103:125-38 (1999 Jan).
2. Hanifin JM. J Invest Dermatol 129(2):320-2 (2009 Feb).
3. Buraczewska I, et al. Br J Dermatol 156(3):492-8 (2007 Mar).
4. Boguniewicz, M, et al. J Pediatr 152:854-9 (2008 Jun).
5. Eichenfield LF, et al. Cutis 80(6Suppl):2-16 (2007 Dec).
6. Wu J. J Drugs Dermatol 7(7 Suppl):s13-6 (2008 Jul).
7. Albring M, et al. Methods Find Exp Clin Pharmacol 5(8):575-7 (1983 Oct).
8. Sur R, et al. Arch Dermatol Res 300(10):569-74 (2008 Nov).
9. Martin K, et al. Parthenolide-free feverfew: an extract with effective anti-irritant activity in vitro. Presented at: 63rd Annual Meeting of the American Academy of Dermatology; New Orleans, LA; February 18-22, 2005. Poster #P1039.
10. Weber TM, et al. J Cosmet Dermatol 5(3):227-32 (2006 Sep).
11. Boralevi F, et al. Allergy 63(2):205-10 (2008 Feb).
12. Ponyai G, et al. J Eur Acad Dermatol Venereol 22(11):1346-55 (2008 Nov).
13. Kisich KO, et al. J Allergy Clin Immunol 122(1):62-8 (2008 Jul).
14. Schlievert PM, et al. Clin Infect Dis 46(10):1562-7 (2008 May 15).
15. Koller DY, et al. Pediatr Allergy Immunol 18(4):335-8 (Jun 2007).
16. Gauger A, et al. J Eur Acad Dermatol Vernereol 20(5):534-41 (2006 May).
17. Chamlin SL, et al. Arch Pediatr Adolesc Med 159(8):745-50 (2005 Aug).

Background

Atopic dermatitis (AD) or eczema is a chronic, relapsing skin condition that can lead to xerosis, pruritus, and patches of dermatitis. Coping with the physical and emotional aspects of AD can significantly impact the quality of life. It is most common in childhood, as many patients seem to outgrow the condition by adulthood. The etiology of AD is complex and not fully understood, but contributing factors include a dysfunctional skin barrier that allows moisture to escape and irritants to enter, as well as inflammatory mediators. There is increasing interest in exploring the feasability and efficacy of using non-drug alternatives as adjuncts to conventional pharmacologic approaches. Lifestyle modifications that can aid AD management will also be reviewed.

Diagnostic Features

• Chronic or chronically relapsing dermatitis
• Typical morphology and distribution (e.g., flexural erythema, excoriations, lichenification, xerosis)
  • Facial and extensor involvement in infants and children; flexural dermatitis and lichenification in adults
• Early age of onset – AD affects up to 20% of children¹
• Intensive itching that can cause disruptive sleep or difficulties in concentration
  • Breaks in the skin from scratching can lead to secondary infection
• Personal or family history of atopy (i.e., asthma, allergic rhinitis, AD)
• Hyperreactivity to environmental triggers

Defects in the Skin Barrier

There is growing data to support the longstanding theory that AD may be caused by a genetic defect in the epidermis, permitting environmental irritants, microbes, and allergens to penetrate, which in turn elicit inflammatory responses.²

• The filaggrin gene contributes to the formation and function of the skin.
• Deviations in the gene coding for filaggrin can cause skin barrier defects that contribute to AD.
• Defects in skin barrier development prevent adequate levels of antimicrobial peptides to form in the epidermis. Consequently, bacterial and viral infections may occur in affected lesions.

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Treatment Options

• Avoidance of triggers
• Emollients/moisturizers
  • Standard adjunct for prevention and maintenance
• Topical corticosteroids
  • The cornerstone of AD therapy
  • Potential for tachyphylaxis, skin atrophy, and systemic side-effects, especially in long-term use
• Topical calcineurin inhibitors (TCIs)
  • Useful when conventional therapies fail or are unsuitable
  • In 2006, an FDA boxed warning was issued for TCIs over concerns of immunosuppression and the potential risk of malignancy following long-term or continuous use.
• Antimicrobials for infection
  • Topical or oral antibiotics may be prescribed to treat infected lesions
  • Overuse or prolonged treatment increase the risk for developing antibiotic resistance
  • Oral antivirals can be used for cases of eczema herpeticum (eczema infected with herpes virus)
• Oral antihistamines for pruritus
  • Often tried for intractable itch, but little evidence exists to support their antipruritic effect
• Systemic corticosteroids, systemic immunosuppressants and phototherapy
  • Reserved for severe disease

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Moisturizing and Bathing

Moisturizers

• Daily moisturization is essential for managing AD, both during and between flare-ups.
• A randomized controlled study demonstrated that moisturizers can improve the barrier function of skin; however, the effects are determined by individual product composition.³
• Basic essential components of moisturizers include emollients and humectants.
  • Emollients provide a protective film by filling-in spaces between cells and restoring lost lipids to prevent transepidermal water loss (TEWL).
    • Commonly used emollients include animal oils, butyl stearate, cocoa butter, lanolin, lipids, mineral oil, petrolatum, and shea butter.
    • Petrolatum is the gold standard emollient; its non-sensitizing and highly occlusive properties are effective against TEWL.
    • Ceramides are lipid molecules that are important components of skin structure; they improve the skin barrier by limiting TEWL and preventing the entry of irritants.
    • AD patients have significantly fewer ceramides in their stratum corneum.
    • Lipids can be replaced topically with a ceramide-dominant emollient.
  • A new class of emollients, now available in the US, aims to replenish certain molecules that are deficient in the skin of AD patients. These nonsteroidal moisturizers are very expensive, but study findings indicate their efficacy and safety for mild to moderate AD.⁴
  • Humectants aid in the absorption and retention of moisture, and soften thickened skin.
    • Commonly used humectants include glycerin, hyaluronic acid, lactic acid, propylene glycol, panthenol, silicones, and urea.
    • Glycerin’s high affinity to attract moisture to the skin makes it the most widely used.
    • Panthenol (vitamin B5) functions as a humectant, emollient, and moisturizer. Studies examining adjuvant care with panthenol showed improved hydration and reduced dryness, itching, and inflammation.⁵

Choosing a Moisturizer

• Generally, the greasier the better. Bland ointments, such as petrolatum, are non-irritating and provide an excellent barrier, but they can be perceived by patients as being too thick.
• Less greasy creams and lotions may be more irritating.
• Some acids (e.g., salicylic acid and lactic acid) and humectants (e.g., urea) can be poorly tolerated by eczematous skin. Avoid their use in infants and small children due to the risk of systemic absorption.

Bathing

• Bathing first, and then applying a moisturizer while the skin is still damp, will help trap moisture in the skin. Medicated treatments should be applied to any dermatitis and moisturizers to unaffected skin.
• Bathing more than once daily is not always practical. Although, during flare-ups, several short baths followed by daytime applications of a moisturizer can be helpful.
• Baths (or showers) should be taken with warm (not hot) water and limited in duration.

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Advancements in the Use of Natural Anti-inflammatories

Increasingly, patients prefer to supplement medical treatments with over-the-counter skin care products that incorporate natural ingredients. Plant-derived extracts are one of the largest categories of additives found in moisturizers. A few notable compounds have emerged following scientific evaluation, which supports their therapeutic benefits for alleviating symptoms associated with AD and other inflammatory skin conditions.⁶

Aloe Vera

• Applications include its use as an anti-inflammatory, analgesic, antipruritic, antioxidant, and wound healing agent.

Chamomile (Matricaria recutita)

• Topical use can relieve skin irritation. The active components (á-bisabolol, á-bisabolol oxide A and B, matricin) inhibit enzymes that mediate inflammation and suppress histamine release.
• Its anti-inflammatory effect is approximately 60% of that elicited by hydrocortisone 0.25%.⁷

Colloidal Oatmeal

• It has multiple active components that include enzymes, flavonoids, lipids, proteins, polyphenols (avenanthramides), polysaccharides, and vitamins.
• Avenanthramides are potent phytochemicals that inhibit the release of proinflammatory cytokines, resulting in reduced contact hypersensitivity and inflammation.⁸
• It also has antioxidant, anti-irritant, antihistaminic, and immunomodulatory effects.
• Colloidal oatmeal is one of few natural ingredients approved as a skin protectant by the US FDA.

Feverfew (Tanacetum parthenium)

• Its broad spectrum of clinical applications is attributable to its potent anti-inflammatory, antioxidant and anti-irritant properties.
• Parthenolides are compounds in feverfew that can produce skin sensitivities. Development of a purified extract that is free of parthenolides has been shown to have strong anti-inflammatory activity through inhibition of proinflammatory cytokine release.⁹

Licorice Extracts (Glycyrrhiza glabra, Glycyrrhiza inflata)

• Glycyrrhiza glabra (contains glabridin) reduces irritation, inflammation, and melanin production.
• Glycyrrhiza inflata (contains licochalcone A) decreases irritation and inflammation.
• Twice daily application of a licochalcone A-containing lotion for 8 weeks by patients with mild to moderate red facial skin produced statistically significant improvements in erythema scores.¹⁰

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Avoidance of Triggers

Avoidance of triggers is a key AD management strategy. Each patient and his or her physician need to identify and eliminate relevant triggers.

Food

• While AD patients are more prone to food allergies (type 1 hypersensitivity), it is unclear if certain foods can cause a flare-up, which is more of a type 4 hypersensitivity reaction.
• If there appears to be a food trigger, parents or patients should keep a diary to track foods eaten and flare-ups. Food elimination diets should be physician supervised.
• If type 1 allergic symptoms develop in response to a particular food, avoid ingestion until testing can be undertaken. If a food source is unclear, it may be useful to involve an allergist.

Aeroallergens

• Certain aeroallergens (e.g., dust mites or seasonal allergens) can trigger AD flares.^11,12
• Confirmatory testing may be useful in refractory
• patients. If results are positive, deploy dust mite prevention strategies (e.g., frequently laundering mattress covers and avoid stuffed toys, feather pillows, duvets, and carpets).

Humidity/Sweating

• Sweating can aggravate itching and humid conditions that increase perspiration can induce flares. Frequently cooling off, changing clothes, and adjusting activities in humid weather can help.
• Heat and sweating can promote nighttime scratching. Recommend one layer each of sleepwear and covering. The bedroom should also be kept cool (but not cold).

Low Humidity/Dry Weather

• Due to the dry weather, most patients have worse flares in the winter. Moisturizing several times per day is crucial. Use of a cool mist humidifier in the bedroom can be helpful.
• Infection
• AD patients are commonly colonized with Staphylococcus aureus (S. aureus) and have problems with S. sureus killing mechanisms.13 This frequently presents as a worsening of AD that is not responsive to therapy. Infected areas can appear as wet, oozing, or crusted lesions that require topical or oral antibiotics.
• S. aureus may drive AD flares through superantigen mechanisms, even in the absence of an actual clinical infection.¹⁴ Therefore, patients who have frequent flare-ups may need strategies to reduce S. aureus colonization and inflammation.

Environmental Irritants

• AD patients can be especially sensitive to dry grass, perfumes or fragrances in skin care products, and certain fabrics (wool and synthetics).
• Wearing cotton clothing can be helpful. Some evidence suggests that specially treated silk or silver-coated fabrics may also be beneficial.^15,16

Chlorine

• Swimming can be a good sport for AD patients, because sweating is not a concern. However, to avoid irritation, they should rinse off thoroughly afterwards and apply a moisturizer.
• There is a lack of data to confirm if salt water or chlorinated pools are better for AD patients.

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Normal Routines

School

• Children with severe eczema may engage in school-avoidance behaviours that are caused by fatigue due to nocturnal pruritus, or anxiety from being teased. These issues must be addressed promptly to re-establish a normal school routine.

Sunscreen

• Many sunscreen products contain irritating ingredients. If regular sunscreens are unsuitable, suggest using sensitive skin formulations or physical sunblocks (e.g., titanium dioxide or zinc oxide).
• A comprehensive sun protection strategy combines regular sunscreen use, avoidance of peak sun exposure times, and wearing hats and protective clothing.

Sleep

• Sleep disturbance from pruritus can be a major problem for many patients and their families, particularly if parents sleep with their AD-afflicted child and help to scratch or restrain their child’s hand to prevent scratching.¹⁷ Both practices should be discouraged and may indicate a need to increase antipruritic therapy and the use of emollients.
• Poor sleep can lead to patient and/or parental difficulties in concentration, irritability, and fatigue.

Top

Additional Tips

• Keep nails short to minimize tissue damage from scratching.
• Keep moisturizing creams in the refrigerator, as the cold sensation is soothing to itchy skin.
• For topical medical therapy, ointments are usually better tolerated than creams or lotions.
• Ask families if sleep routines are satisfactory and if sleep is disturbed. Many families do not volunteer this information to physicians.
• Patients should be steered toward good sources of information (e.g., http://www.eczemahelp.ca).

Conclusion

Successful AD management is best undertaken with a step-wise approach that considers multiple factors including disease severity, therapeutic side-effects, patient preferences, itch intensity, and sleep quality. As well, psychosocial impacts from AD cannot be overlooked. The regimented use of moisturizers can improve the skin barrier and significantly reduce xerosis and itch. As such, it can serve as useful adjunctive care for maintenance and flares. The new research realm directed at the epidermal barrier and the important immune factors carries the hope that innovative therapeutic approaches will lead to reduced infections and improved management of AD patients.

Top

References

1. Williams H, et al. Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood. J Allergy Clin Immunol 103:125-38 (1999 Jan).
2. Hanifin JM. Evolving concepts of pathogenesis in atopic dermatitis and other eczemas. J Invest Dermatol 129(2):320-2 (2009 Feb).
3. Buraczewska I, et al. Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial. Br J Dermatol 156(3):492-8 (2007 Mar).
4. Boguniewicz, M, et al. MAS063DP is effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study. J Pediatr 152:854-9 (2008 Jun).
5. Eichenfield LF, et al. Natural advances in eczema care. Cutis 80(6Suppl):2-16 (2007 Dec).
6. Wu J. Anti-inflammatory ingredients. J Drugs Dermatol 7(7 Suppl):s13-6 (2008 Jul).
7. Albring M, et al. The measuring of the anti-inflammatory effect of a compound on the skin of volunteers. Methods Find Exp Clin Pharmacol 5(8):575-7 (1983 Oct).
8. Sur R, et al. Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity. Arch Dermatol Res 300(10):569-74 (2008 Nov).
9. Martin K, et al. Parthenolide-free feverfew: an extract with effective anti-irritant activity in vitro. Presented at: 63rd Annual Meeting of the American Academy of Dermatology; New Orleans, LA; February 18-22, 2005. Poster #P1039.
10. Weber TM, et al. Skin tolerance, efficacy, and quality of life of patients with red facial skin using a skin care regimen containing Licochalcone A. J Cosmet Dermatol 5(3):227-32 (2006 Sep).
11. Boralevi F, et al. Epicutaneous aeroallergen sensitization in atopic dermatitis infants-determining the role of epidermal barrier impairment. Allergy 63(2):205-10 (2008 Feb).
12. Ponyai G, et al. Contact and aeroallergens in adulthood atopic dermatitis. J Eur Acad Dermatol Venereol 22(11):1346-55 (2008 Nov).
13. Kisich KO, et al. Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3. J Allergy Clin Immunol 122(1):62-8 (2008 Jul).
14. Schlievert PM, et al. Superantigen profile of Staphylococcus areus isolates from patients with steroid-resistant atopic dermatitis. Clin Infect Dis 46(10):1562-7 (2008 May 15).
15. Koller DY, et al. Action of a silk fabric treated with AEGIS in children with atopic dermatitis: a 3-month trial. Pediatr Allergy Immunol 18(4):335-8 (Jun 2007).
16. Gauger A, et al. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. J Eur Acad Dermatol Vernereol 20(5):534-41 (2006 May).
17. Chamlin SL, et al. The price of pruritus: sleep disturbance and cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med 159(8):745-50 (2005 Aug).