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112-1 ATOPIC DERMATITIS The Itch that Erupts when Scratched . . . . . . . . . . . . Level I Rebecca M.T. Law, PharmD CASE SUMMARY A 3½-year-old girl who has had atopic dermatitis since age 6 months has had a worsening over the past 2–3 weeks. The child also has behavioral issues likely related to stressors such as recent placement in day care; and there are other aggravating factors. The child requires both nonpharmacologic and pharmacologic management of the atopic dermatitis flare. Nonpharmacologic management includes avoidance of triggers and social aspects such as behavior modification for the child, counseling for the parents, appropriate skin care, and environmental changes. Pharmacologic agents include a medium-strength corticosteroid topical cream, copious use of scent-free moisturizers, pimecrolimus or tacrolimus if not controlled, and control of itching. QUESTIONS Problem Identification 1.a. Create a drug therapy problem list for this patient. • Julia has signs and symptoms of atopic dermatitis insufficiently managed with hydrocortisone cream and moisturizers. • Recent stressors (eg, placement in day care) and related behavioral issues are likely exacerbating Julia’s atopic dermatitis. • Julia’s caregivers (her parents) are under stress. They require social support and psychological assistance to prevent inadequate or inappropriate care of Julia. 1b. What signs and symptoms of atopic dermatitis does this patient demonstrate? • Generally dry skin (xerosis).1,2 In atopic dermatitis, transepidermal water loss is increased.3 • There are likely pruritic papules in flexure areas and excoriations from scratching. There is some bleeding but areas do not appear to be infected. Some cracking skin lesions are seen behind the ears and knees. There are no lesions on the extensor parts of the body. Sparing of the skin on top of the nose is a characteristic feature (known as the “headlight sign”).1,2 The groin and axillary region are also usually spared.3,4 • There is itch-induced scratching and subsequent excoriations. Pruritus is a quintessential feature of atopic dermatitis, and a diagnosis cannot be made if there is no history of itching.1–4 Scratching or rubbing itchy, atopic skin characterizes this eczema.4 This can further irritate the skin, increase inflammation, and exacerbate itchiness.1 Itching is especially problematic during sleep when conscious control of scratching is lost.1 Julia’s mother has sewn mittens on her pajamas to prevent her from scratching. Also, once there is pruritus, the likelihood that surrounding skin (whether inflamed or noninflamed) will react to light stimuli with itching is increased; this is called allokinesis and is typical of atopic dermatitis. Allokinesis describes a state • Serum IgE is usually elevated in patients with atopic dermatitis1,4 and the level may correlate somewhat with AD disease severity.4 However, elevated allergen-specific IgE levels can be found in 55% of the general US population.4 There is a genetic predisposition in patients with atopy to demonstrate Th2 predominance—hence increased Th2 cell activity.3,4 Several candidate genes that encode cytokines involved in the regulation of IgE synthesis have been identified, notably on chromosome 5q31-33.5 Increased Th2 activity leads to release of IL-3, IL-4, IL-5, IL-10, and IL-13, which causes eosinophilia, increases IgE, and increases the growth and development of mast cells.3 These cytokines also affect B cell maturation, causing a genomic rearrangement that favors isotype class switching from IgM to IgE.5 In addition, increased serum IgE antibodies to a particular food is consistent with a food allergy,1,2 which is common in patients with atopic dermatitis— and Julia has multiple food allergies. • Eosinophilia in peripheral blood. • Positive RAST (radioallergosorbent) test. This is an allergenspecific IgE antibody test used to screen for allergy to a specific substance or substances; in some cases it may be used to monitor immunotherapy or to see if a child has outgrown a specific allergy. Positive (elevated) results usually indicate an allergy to a suspected or known allergen. However, the level of IgE may not correlate with the severity of an allergic reaction, and the IgE level may remain elevated for years after an allergy has been outgrown. • In addition, Julia demonstrates behavioral problems, which are likely related to the stress of beginning day care. She has lots of temper tantrums, appears unhappy, has lost her toilet training and is using diapers again. • A clinically useful set of criteria for the diagnosis of atopic dermatitis is as follows: Essential features (must be present) are pruritus and eczema (acute, subacute, and chronic); important features (usually present and supports the diagnosis) are early age of onset, atopy, and xerosis.4 Atopy can be demonstrated by a personal and/or family history, and by IgE reactivity.4 Julia’s signs and symptoms are all consistent with a diagnosis of atopic dermatitis, perhaps exacerbated by stress. 1c. What risk factors or aggravating factors may have contributed to the patient’s atopic dermatitis flare? • Strong family history of atopic diseases and food allergies: severe shellfish allergy in Julia’s father, hay fever in her mother, multiple food allergies in her paternal aunt, asthma in her maternal grandmother, infantile eczema in her paternal first cousin, and severe peanut allergy in her maternal first cousin. The strongest risk factor for atopic dermatitis is a parental history of atopy or eczema, with maternal atopy possibly more predictive than paternal atopy.2,4 • Genome-wide scans have identified atopic dermatitis-related loci on 1q21, 3q21, 16q, 17q25, 20p, and 3p26.3 The filaggrin gene (FLG) on chromosome 1q21.3 has been found to encode a key protein in epidermal differentiation.5 Mutations of FLG were identified in 30% of European patients Copyright © 2017 by McGraw-Hill Education. All rights reserved. Atopic Dermatitis Poh Gin Kwa, MD, FRCPC CHAPTER 112 112 wherein a normally nonpruritic stimulus induces pruritus in the skin surrounding the active lesion; this is experienced by patients with atopic dermatitis as “pruritic attacks” when their skin is touched accidentally by mechanical factors such as clothing. Interleukin-31 (IL-31), a strongly pruritogenic cytokine, has been implicated as a major factor in the genesis of pruritus in atopic dermatitis, along with other cytokines and chemokines.5 However, IL-31 and others are not sensitive or specific enough to be biomarkers for atopic dermatitis.4 112-2 SECTION 14 Dermatologic Disorders with atopic dermatitis, and distinctive FLG mutations have also been reported in Japanese patients.5 Mutations of FLG confer a risk for early-onset atopic dermatitis4,5 and for more severe, persistent disease.4 Other genetic variants coding for other epidermal structures may also be involved. As discussed earlier, genes encoding major elements of the immune system are also involved. Thus, atopic dermatitis appears to be a complex genetic disease with gene–gene interactions and gene–environment interactions. The two major groups of genes involved are genes encoding epidermal or other epithelial structural proteins, and genes encoding major elements of the immune system.3–5 • Environmental influences including lifestyle changes over the past few decades have led to altered prevalences of allergic diseases including atopic dermatitis.3 Environmental factors may include climate, urban versus rural living, diet, breastfeeding and time of weaning, obesity, and pollution/tobacco smoke.4,6 The largest international study of the prevalence of atopic dermatitis (ISAAC—International Study of Asthma and Allergies in Childhood) has shown that prevalence differs from country to country, with large increases in prevalence occurring in developing countries and a decrease in prevalence in developed countries.7 The hygiene hypothesis attributes increasing atopic dermatitis to reduced exposure to various childhood infections and bacterial endotoxins.3,4,6 Support for the hygiene hypothesis includes the following observations: urban living increases risk; exposures to endotoxin, farm animals (even the pregnant mother), and dogs are protective; attending day care within the first year of life is protective; and the consumption of unpasteurized milk and acquired helminth infections may be protective but are not recommended due to health risks.4 Julia just started day care about a month ago (at age 3½). The ISAAC study also suggested that a maximum prevalence plateau of about 20% has emerged.7 Refer to the corresponding Pharmacotherapy textbook chapter on atopic dermatitis for additional details. • Strawberries, raspberries, tomatoes, and eggs appear to be aggravating factors for Julia. This is consistent with the age of onset and the extent of atopic dermatitis in this child. Patients with atopic dermatitis have a higher prevalence of food allergy than those in the general population,1 particularly those of younger age and with more severe disease.6 However, the role of food antigens in the pathogenesis of atopic dermatitis is controversial.3 A current belief is that food allergy may be caused by atopic dermatitis because, in most patients with both conditions, atopic dermatitis precedes the food allergy. In general, the worse the atopic dermatitis and the younger the child, the more likely it is that some type of food allergy is present.1,6 The most common allergenic foods are eggs, milk, peanuts, wheat, soy, and fish.1 Julia is reported to be sharing other children’s foods at the day care; this increases the likelihood that she has recently been exposed to an allergenic food. • Starting day care appears to be an aggravating factor for Julia, and she is still exhibiting clinging behavior after a month. Other stressors for Julia may include being taken care of by various babysitters rather than her parents (the parents’ stressful lifestyle). Emotional factors may play a role in atopic dermatitis.1 • Being bottle-fed from 2 months of age may be a risk factor. Studies on allergies and breastfeeding indicate that breastfeeding an infant for at least 4 months may protect the child from developing allergic conditions.1 • Being exposed to cigarette smoke (the mother has restarted smoking) may be a risk factor. Copyright © 2017 by McGraw-Hill Education. All rights reserved. • Environmental aeroallergens (the child had been left by the babysitter on the floor/carpet) may have been contributing factors. Dust mites, pollens, molds, and dander from animal hair or skin may worsen the symptoms of atopic dermatitis.1,6 Reactivity to aeroallergens seems to increase with age, and skin contact with an aeroallergen may trigger eczematous skin lesions in some patients.6 1d. Could the patient’s signs and symptoms be caused by a drug? • No. The child is currently receiving topical medications for atopic dermatitis, which should not cause her current signs and symptoms. • Oral diphenhydramine used to relieve the itch should also not cause atopic dermatitis, and the drowsiness it causes may be relaxing and may promote more restful sleep. Desired Outcome 2.What are the treatment goals for this patient? • Control the itching. Itching is one of the most bothersome features of atopic dermatitis, and in this child it has led to excoriations. Furthermore, because of the child’s atopic skin, she might experience parental touching differently; and an altered tactile experience in early infancy could affect the development of stable physical and emotional boundaries; some patients may use scratching to define their physical boundaries and needs.8 Body image and self-esteem can be affected as the child grows. Selfesteem is often diminished in patients with atopic dermatitis. • Control the atopic dermatitis. • Eliminate any food triggers and environmental aeroallergens. • Prevent future flare ups of atopic dermatitis. • Minimize drug toxicity. • Provide cost-effective therapies. • Provide adequate relief of the stressors affecting the child (to help control her behavior). • Provide social support and psychological assistance/counseling for the parents to ensure continuing appropriate care of the child. • Improve the quality of life (for Julia and her parents). Therapeutic Alternatives 3.What feasible nonpharmacologic and pharmacologic alternatives are available managing this patient’s pruritus and atopic dermatitis? Pruritus • Cool compresses and tepid baths, followed by liberal use of moisturizers (see below) are important nonpharmacologic measures to relieve itching.9,10 • Oatmeal baths, lotions containing menthol or phenol, EMLA cream (rarely used), and 5% doxepin cream (rarely used) are potential topical pharmacologic treatments for reducing pruritus.8 Short-term adjunctive use of topical doxepin may reduce pruritus but is limited by side effects. • Topical corticosteroids decrease pruritus9 and also control the underlying atopic dermatitis. • Tacrolimus and pimecrolimus are topical immunomodulating agents that appear to be the most promising antipruritic agents for atopic dermatitis.2,3 • Oral antihistamines, antidepressants (doxepin, SSRIs), and anxiolytics are systemic pharmacologic therapies sometimes used 112-3 Atopic dermatitis • Both nonpharmacologic and pharmacologic management strategies are important in controlling the disease. These include minimizing preventable risk factors such as stress, avoiding triggers and known allergens, environmental control, proper bathing and moisturizing techniques, use of scent-free moisturizers, medium-strength topical corticosteroids, topical immunomodulators, and phototherapy.1–4,9–11 • Nonpharmacologic management strategies are important in controlling flare-ups of atopic dermatitis and reducing its primary symptom (itching). Minimizing preventable risk factors and eliminating or avoiding what provokes the flare ups should be the objective.6 Regardless of disease severity, basic management strategies should be implemented for every patient with atopic dermatitis. These strategies include: proper skin care (discussed below), antiseptic measures (ie, dilute bleach baths—discussed below), and patient-specific trigger/irritant avoidance (discussed below).10 Acute treatment is added to these baseline maintenance strategies for flares. • Hydration is crucial, and adequate skin hydration is a fundamental part of managing atopic dermatitis.1,9,10 Transepidermal water loss is greater in atopic skin than in normal skin. Thus, any measures to improve skin moisturization (discussed below) would be beneficial. It is recommended that the humidity in the home be kept at or above 50% and the room temperature be kept on the cool side. • Identifying food or environmental allergens/triggers specific to the patient may be important. If triggers can be identified, avoidance may lead to longer intervals between flares and even complete disease clearance in some cases.10 Nonspecific triggers may include harsh soaps, detergents, wool and other abrasive fabrics, tight-fitting clothing, certain chemicals, airborne irritants (tobacco smoke and air pollution), and extremes or transitions in temperature and humidity.10 Relevant allergens differ by age, with young children more likely to have food allergies and older children and adults more likely to be sensitive to aeroallergens.10 The National Institute of Allergy and Infectious Diseases (NIAID) Food Allergy Expert Panel suggests limited food allergy testing (ie, cow’s milk, eggs, wheat, soy, and peanut) if a child <5 years old has moderate-to-severe atopic dermatitis and (1) persistent disease despite optimized therapies; (2) reliable history of an immediate allergic reaction after ingesting a specific food; or (3) both.6 Tests include skin prick testing (SPT) and serum-specific IgE levels using in vitro assays such as radioallergosorbent (RAST) testing or immunoCAP testing.6,10 • Managing identified food allergies is important. The role of food as a trigger or clinical association should be considered in all • Reducing dust mites or molds in the house may help reduce allergen exposure (eg, encasing mattresses and pillows in dustmite protective covers, washing bedding regularly with hot water, removing carpets if possible, and frequent vacuuming of bare floors and any carpeting—especially if the child sits/plays on the floor). However, evidence to support the routine use of house dust mite covers is limited.6 • Avoiding woolen or other rough/irritating fabrics may be helpful for both child and parents.1–3,6,10 Smooth clothing may minimize skin irritation, and soft cotton or silk are preferred. There are a few controlled studies showing that specialty silk garments may improve atopic dermatitis severity scores. However, it is unclear whether silk and specialty silks impregnated with antibacterial agents provide significantly more improvement than soft cotton.6 • Tobacco smoke may be an irritant and should be avoided.1,10 Air pollution may also be an irritant.10 However, study results are inconsistent, and personal or secondhand/household smoking status do not appear to significantly affect the development of atopic dermatitis, even though smoking is detrimental to those with asthma and has many other negative health risks.4 Because the mother has restarted smoking, she should be encouraged to use other methods to handle her stress and enroll in a smoking cessation program if needed. The mother should also avoid using perfumes or any fragranced products (eg, fabric softener sheets, deodorant sprays, hair sprays, and room deodorants). • Minimizing stress is also important. Psychotherapeutic approaches with a combination of educational and psychological interventions may be beneficial. • Educating patients and caregivers is an important intervention.6 A written action plan (regarding when to apply moisturizers and topical medications, when to step-up or step-down treatment, when to seek medical advice, what triggers to avoid) may reinforce teachings6 and is critical to ensuring good long-term Copyright © 2017 by McGraw-Hill Education. All rights reserved. Atopic Dermatitis • Topical antihistamines should be avoided due to their potentially irritant or sensitizing effects.2 infants with moderately severe to severe atopic dermatitis. However, the role of food antigens in the pathogenesis of atopic dermatitis remains controversial, as discussed earlier.3 Food allergies may coexist and do represent important triggers in a small subset of individuals with atopic dermatitis,6,10 but the true frequency of food allergies causing an isolated flare of disease is probably low.6 Thus restricted elimination diets (eg, exclusion of eggs, cow’s milk, peanuts, nuts, and fish especially in children under age 2) which was once thought to be helpful is currently a controversial practice, and most physicians currently do not withdraw food from the diet.3 Multiple dietary restrictions and long-term dietary avoidance should only be done with documented, clinically relevant food allergies.6 Food elimination diets based solely on the findings of food allergy test results are not recommended for managing of atopic dermatitis.6 Excessively restrictive diets, especially in atopic children, have resulted in weight loss, poor growth, calcium deficiency, hypovitaminosis, and kwashiorkor.6 Current research attempts to desensitize patients by inducing tolerance: results using desensitization protocols from limited studies have shown benefit in a few patients with food allergies. Avoidance of known offending foods in the particular patient (ie, tomatoes, strawberries, raspberries, and eggs for Julia) may improve skin symptoms in a subset of patients with moderately severe to severe atopic dermatitis.6 Sometimes, elimination of a particular food may be difficult, and recurring flare-ups may be caused by missed hidden offending food ingredients (eg, a utensil used to serve cookies with or without peanut butter can contaminate the peanut-free cookie with enough peanut protein to cause a reaction; egg may be hidden in pasta, sweets, or cake). 4,6 CHAPTER 112 for itching. There is little evidence that sedating or nonsedating antihistamines are effective when used alone for the itch in atopic dermatitis.8 Several trials with fexofenadine and cetirizine used in conjunction with topical corticosteroids showed some benefit (fexofenadine further reduced the pruritus symptom score when added to a topical corticosteroid, and cetirizine reduced the duration of corticosteroid use).2 Other recent trials with loratadine and chlorpheniramine did not show benefit.2 However, sedating antihistamines such as diphenhydramine may reduce nighttime scratching and promote more restful sleep when taken at bedtime.1,11 These may be useful for patients with significant sleep disruption due to itch, allergic dermatographism, or allergic rhinoconjunctivitis.8 1–3 112-4 SECTION 14 Dermatologic Disorders treatment adherence.10 A formal, 6-week educational program of patients and their families, led by an interprofessional team having dermatologic, nutritional, and psychological components, resulted in decreased severity of disease in a randomized, controlled trial with 825 children and adolescents with moderate-to-severe atopic dermatitis.6 • Appropriate skin care is crucial in preventing flare-ups.1,3,9,10 A daily skin care routine should include the following: ✓Using scent-free moisturizers ad lib throughout the day. Large quantities can be used. There are presently no recommendations regarding the appropriate amount or dosing frequency of moisturizers.9 ✓ Bathing in lukewarm water (never hot) for 5–10 minutes one or more times daily.9 Soaking daily for 20 minutes followed immediately by application of topical agents (eg, corticosteroids) without towel drying is known as the “soak and smear” technique and is useful when the topical agent alone is inadequate.9 Twice-daily bathing during disease flares may also be a useful method for enhancing skin penetration of topical therapies and for debridement of crusting and staphylococcal colonization. Dilute bleach baths with intranasal topical mupirocin may be helpful in moderate-tosevere atopic dermatitis patients with frequent bacterial skin infections and may be particularly useful as maintenance therapy.9 There is insufficient evidence to recommend other routine bath additives (such as bath oils) or topical antimicrobial preparations (such as antiseptics, antibacterial bath soaps) other than dilute bleach baths.9 ✓The skin should be lightly towel dried except when the “soak and smear” technique is used (pat to dry, avoid rubbing, or brisk drying).9 ✓Moisturizer (scent-free) should then be applied while the skin is still moist or slightly damp (within 3 minutes of towel drying).2 Some fragrance-free moisturizers include Aveeno Moisture Cream, Cetaphil, Neutrogena Hand Cream, and Vanicream. Lotions may be used on the scalp and other hairy areas and for mild dryness on the face, trunk, and limbs; creams are more occlusive than lotions; ointments are the most occlusive and can be used for drier, thicker or more scaly areas.2 Occlusive moisturizers are the best since they slow transepidermal water loss by providing a layer of oil on the skin surface, increasing the moisture content of the stratum corneum. ✓ Limited use of nonsoap skin cleansers that are neutral to low pH, hypoallergenic, and fragrance free is recommended.9 Lipid-free and fragrance-free skin cleansers may be particularly advantageous (eg, Cetaphil Gentle Skin Cleanser, Free and Clear Liquid Cleanser, Spectro Jel for sensitive problem prone skin). Aquanil, Dove, Neutrogena, and pHisoderm sensitive skin products have also been recommended as low irritant products, and some are lipid-free. ✓Avoiding alcohol-containing topical products including lotions, swabs and wipes (they may be drying). ✓The use of specific laundering techniques, such as double rinsing, detergents, or other laundry products cannot be recommended for atopic dermatitis treatment because of the lack of clinical studies.6 • Pharmacologic management strategies: ✓Topical corticosteroids (TCS) are the standard of care to which other treatments are compared.9,10 However, despite their extensive use, there is limited data regarding optimal TCS concentrations, duration and frequency of therapy, and quantity of application.1,2,9 The use of long-term intermittent Copyright © 2017 by McGraw-Hill Education. All rights reserved. TCS appeared to be beneficial and safe in two randomized controlled studies. To maximize the anti-inflammatory benefit and minimize adverse effects, the choice of TCS should ideally be matched with the severity and site of disease.3 Low-potency TCS, such as hydrocortisone 1% cream, are suitable for the face, and medium-potency TCS such as betamethasone valerate 0.1% may be used for the body. For longer-duration maintenance therapy, low-potency TCS are recommended.9 There is no established optimum regimen for controlling flare-ups—starting with a short burst of high-potency TCS to rapidly control active disease followed by a rapid taper in potency is equally acceptable as using the lowest-potency agent thought to be needed and then adjusting upward if treatment fails.9 Although twice-daily application is the usual clinical practice, there is some evidence of efficacy with once-daily use of some potent TCS.9 Refer to the psoriasis chapter of the Pharmacotherapy textbook for a corticosteroid potency comparison chart. Ointment bases are preferred due to their occlusive properties. There is still limited data regarding optimal duration and frequency of application. There should be a beneficial response in 10–14 days.2 If no improvement is seen, a dermatologist should be consulted for further assessment. Daily TCS applications should continue until the inflammatory lesions are significantly improved, which may take up to several weeks at a time.9 Once disease activity is controlled, TCS should be tapered to a less potent preparation and used intermittently (eg, once or twice weekly) or withdrawn (with moisturizers used alone). Applying a TCS once or twice weekly to areas of the patient’s body where frequent/repeated flare-ups occur has reduced rates of relapse for patients who experience frequent flare-ups at the same body sites.9 Corticosteroids should not be used continuously for more than several weeks because they can cause cutaneous side effects such as skin atrophy, stretch marks (striae), purpura, telangiectasias, focal hypertrichosis, and acneiform or rosacea-like eruptions, as well as less common systemic side effects including adrenal suppression, infections, and growth retardation in children.9,10 Growth retardation may be related to the chronicity of the illness rather than to corticosteroid use or dietary factors. Although tachyphylaxis is a clinical concern, there is no experimental documentation.9 Although cataracts and glaucoma are possible with systemic corticosteroid use, a definite association with TCS is unclear.9 Nevertheless, minimizing use at periocular sites is prudent.9 ✓Wet wrap therapy (WWT) involves covering TCS application with a wetted first layer of tubular bandages, gauze, or a cotton suit, followed by a dry second/outside layer. WWT has been shown to quickly reduce disease severity and can be used in patients with significant flare-ups and/or recalcitrant disease in either hospital or ambulatory settings.9 WWT provides occlusion, decreases water loss, and acts as a physical barrier against scratching. The wrap can be worn from several hours to 24 hours at a time, depending on patient tolerance.9 ✓Topical immunomodulators such as the calcineurin inhibitors tacrolimus ointment (Protopic) and pimecrolimus cream (Elidel) are approved for atopic dermatitis in adults and children older than age 2.1–4,9,10 Although clinical trials conducted in younger infants (eg, 2–23 months old) also showed significant efficacy without appreciable adverse effects, use in children younger than age 2 is not FDA approved. Calcineurin inhibitors have been shown to reduce 112-5 ✓Tar preparations are another topical alternative that may be beneficial.9 However, there are few clinical trials and use is limited by poor adherence. Tar preparations can be malodorous, and adverse effects include tar folliculitis, acneiform eruptions, irritant dermatitis, photosensitivity, and a burning sensation. ✓Topical phosphodiesterase inhibitors are a new class of antiinflammatory treatments that are presently available only in clinical trials.9 ✓Phototherapy (ie, ultraviolet light therapy) is effective and may also be corticosteroid-sparing, allowing for the use ✓Systemic therapies are not routinely used in managing atopic dermatitis. Cyclosporine is effective for severe or recalcitrant atopic dermatitis but has limiting side effects including nephrotoxicity and hypertension. Systemic corticosteroids may be effective for rapid disease suppression, but little evidence exists to support their use. Rebound flaring occurs with short courses of oral corticosteroids,11 and long-term side effects are limiting and of particular concern in the growing child. Thus they are generally not recommended due to an unfavorable risk-benefit profile.11 Recombinant interferon gamma or oral methotrexate may be effective in a subset of patients with severe disease. With respect to the efficacy of azathioprine, mycophenolate mofetil, and intravenous immunoglobulin (IVIG), the limited data are primarily in small case series or open-label studies in adults with recalcitrant atopic dermatitis.11 Biologic agents are not currently approved for atopic dermatitis, and theoretically, using protein-based therapies may be inherently risky in a patient population more prone to developing IgE-sensitization to protein antigens. There are a few case reports and small case series, but additional research is needed.11 Oral antihistamines have mixed evidence of efficacy for disease control, except for sedating antihistamines used at night for patients with poor sleep due to pruritus.11 ✓Probiotics may prove to be beneficial for treatment of atopic dermatitis. Probiotics are live microorganisms that confer a health benefit on the host when administered in adequate amounts. However, a 2010 review of 18 prevention or treatment studies concluded that results are mixed.12 One prevention study showed a 50% reduction in the incidence of atopic dermatitis, whereas another study showed no reduction. The results sometimes appeared to depend on the specific strain of probiotics used. Treatment studies also demonstrated conflicting results.12 Presently, issues including which organisms are effective, optimal dosing, duration of therapy, efficacy and safety issues all require further investigation, although adverse effects have been uncommon. Thus, at the moment there is insufficient evidence to support a recommendation for using probiotics for prevention or treatment of atopic dermatitis.6 Optimal Plan 4.What treatment regimen is best suited for this patient? • Institute all of the nonpharmacologic management strategies described previously that are applicable in this situation, such as avoiding woolen or other rough fabrics, appropriate skin care and proper bathing techniques, minimizing food triggers and allergens. The teachers at day care should be instructed to monitor that Julia is not sharing other children’s food. In addition, the following psychotherapeutic approaches, combining educational and psychological interventions, should be provided: ✓Counseling for the parents regarding handling of stress and behavior modification for Julia (who has lost her toilettraining and has behavioral issues such as frequent tantrums). Encourage the parents to seek additional social support. Copyright © 2017 by McGraw-Hill Education. All rights reserved. Atopic Dermatitis ✓Prescription emollient devices (PEDs) are barrier creams that act to repair the damaged skin barrier and may provide some anti-inflammatory activities.9 The FDA has approved their use as “medical devices,” (which is a less rigorous process), based on the assertion that they serve a structural role in skin barrier function and do not exert their effects by any chemical actions.9 There is limited efficacy and safety data.9 Products include Atopiclair, which contains hyaluronic and glycyrrhetinic acids, MimyX, which contains N-palmitoylethanolamine, and EpiCeram, which contains ceramides, cholesterol and free fatty acids. These are generally recommended for use two to three times daily.9 of lower potency TCS. Phototherapy is a recommended second-line intervention for treatment of atopic dermatitis and may be used for acute or maintenance therapy in children and adults.11 Patients require eye protection during UV treatments. Adverse effects include erythema, skin burning (“sunburn”), pruritus, pigmentation, photoaging, and risk of skin cancer. CHAPTER 112 the extent, severity, and symptoms of atopic dermatitis in children and adults.9 Due to continuing concerns regarding a possible risk of cancer, both drugs are recommended for use as second-line treatments for short-term and noncontinuous chronic use in atopic dermatitis when the use of TCS is ineffective or inadvisable.9 They may be appropriate in patients with corticosteroid-related side effects, patients with large body-surface areas of disease, patients unresponsive to corticosteroids, or where treatment with corticosteroids is otherwise inadvisable. Unlike topical corticosteroids, calcineurin inhibitors can be used on all body locations for prolonged periods.2 They may be used as two to three times weekly chronic therapy for long-term maintenance10 and may also be used as steroid-sparing agents (sequentially or concomitantly with TCS), although clinical data are limited.9 Pimecrolimus cream provides a rapid and sustained effect in controlling pruritus, with benefit often seen within 48 hours. The relief of pruritus is seen across a diverse patient population in terms of age (>3 months) and severity of disease. It provides rapid and sustained relief of exacerbations and minimizes recurrence better than conventional treatment (ie, intermittent topical corticosteroids for disease flare-ups). The cream should be applied at the first signs of a flare (eg, local redness and pruritus) and continued for 5–7 days after clearance of lesions.2 Tacrolimus ointment also provides a rapid and sustained benefit in controlling signs and symptoms of atopic dermatitis in children and adults with moderate-to-severe disease. The 0.03% ointment is approved for moderate-to-severe disease for ages 2 and older, whereas the 0.1% ointment is limited to ages 16 and older. The most common adverse effect of both agents is transient discomfort (burning sensation) at the application site. This usually disappears within 2–3 days. There does not appear to be an increased risk of bacterial or viral infections, although there is a possible risk of cutaneous malignancy; sun protection is recommended.2 A high sun protection factor (SPF) broad-spectrum sunblock (eg, SPF 30 or higher) should be applied daily to all exposed skin, especially for those with the highest risk of developing skin cancers (eg, patients receiving phototherapy). 112-6 SECTION 14 ✓Parental education regarding environmental changes such as reducing dust mites and removing carpets, stopping smoking, and education about atopic dermatitis. Encourage the mother to seek a smoking cessation program if needed. Provide a written action plan with specific management strategies tailored for Julia’s atopic dermatitis (see Ref. #10 for details).10 Dermatologic Disorders • Give diphenhydramine 6.25 mg PO at bedtime nightly, and consider giving it every 4–6 hours as needed (maximum 37.5 mg/day) for not more than 14 days. • Apply a medium-strength corticosteroid (eg, betamethasone dipropionate 0.1% cream) twice daily to lesions for 10–14 days and reassess. Use hydrocortisone 1% ointment on face and skinfolds. Once the disease activity is controlled, either withdraw the corticosteroid cream or use it intermittently if longterm therapy is needed to control flare-ups. The least potent preparation that maintains adequate control of the disease should be selected. If no improvement is seen in 14 days, start pimecrolimus 1% cream and continue for 5–7 days after the lesions have cleared, or continue intermittently as maintenance. parents should be taught how to apply the topical corticosteroid cream, some side effect information for the medications, the appropriate daily skin care routine for Julia, the triggers to avoid, and appropriate environmental control measures, as discussed previously. The written action plan should be patient-specific for Julia with detailed courses of action about treatment of acute flares, maintenance/control therapies, and other management strategies (see Ref. #10). • The parents should be provided with personal psychologic assistance and social support to ensure compliance with the child’s care—both overall care and specific care for the atopic dermatitis condition. Ensuring that Julia has a restful night’s sleep (and hence the mother’s sleep) will help ease her stress. As mentioned earlier, the parents would benefit from stress management instruction. • In addition, Julia’s mother should be encouraged to enroll in a smoking cessation program. This is important for both her and Julia. Cigarette smoke may be a trigger for Julia’s atopic dermatitis and may potentially increase her risk of developing asthma. • Apply petroleum jelly to the affected areas ad lib. Outcome Evaluation 5.What efficacy and adverse effects monitoring is needed for the management strategies you recommended? Efficacy Monitoring • Itching should improve in 3–4 days. • The appearance of the atopic skin should improve within 3–7 days, definitely by 10–14 days. • The skin should appear less dry over time with continued use of moisturizers and appropriate skin care. • It is important to involve the parents in monitoring their child’s progress and ensuring that excoriated/bleeding lesions do not become secondarily infected. • It is important to also monitor for behavioral improvements in Julia. If allowed to continue, stress and lack of social interaction may lead to further psychological issues. Adverse Effect Monitoring • Diphenhydramine may cause dry mouth and daytime sleepiness. • Topical corticosteroids may cause local side effects including skin atrophy, fungal or bacterial skin infections, striae, skin pigmentation, and acne, especially if use is prolonged. Systemic side effects including HPA-axis suppression, growth suppression, osteoporotic changes, and Cushing’s syndrome are also possible especially with high-potency topical corticosteroids or weaker ones used under occlusion.9 • If pimecrolimus is required, there may be some transient burning at the application sites. Patient Education 6.How would you inform the patient’s caregiver about the treatment regimen to enhance compliance and ensure successful therapy? • The importance of adequate and appropriate education of the patient’s caregivers about atopic dermatitis and its management cannot be overemphasized. Julia’s parents should be informed about the prognosis including time to healing and possible effects on emotional health, body image and self-esteem. The Copyright © 2017 by McGraw-Hill Education. All rights reserved. REFERENCES 1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on Health: Atopic Dermatitis. US Department of Health and Human Services, 2013. NIH Publication No. 09-4272. Available at: http://www.niams.nih.gov/health_info/atopic_dermatitis/default.asp. Accessed September 2, 2015. 2. Lynde C, Barber K, Claveau J, et al. Canadian practical guide for the treatment and management of atopic dermatitis. J Cutan Med Surg (incorporating Medical and Surgical Dermatology), published online June 28, 2005. Available at: http://www.springerlink.com/content /r5432000056r2748/fulltext.html. Accessed September 2, 2015. 3. Kim BS. Atopic Dermatitis. Medscape eMedicine updated July 1, 2015. Available at: http://emedicine.medscape.com/article/1049085-overview. Accessed August 29, 2015. 4. Eichenfield LE, Tom WL, Chamlin SI, et al. Guidelines of care for the management of atopic dermatitis—Section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol 2014;70:338–351. 5. Bieber T. Mechanisms of disease: atopic dermatitis. N Engl J Med 2008;358:1483–1494. 6. Sidbury R, Tom WL, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis—Section 4: Prevention of disease flares and use of adjunctive therapies and approaches. J Am Acad Dermatol 2014; published online Sept. 25, 2014. Available at: http://dx.doi .org/10.1016/j.jaad.2014.08.038. 7.DaVeiga SP. Epidemiology of atopic dermatitis: a review. Allergy Asthma Proc 2012;23:227–234. 8. Koblenzer CS. Itching and the atopic skin. J Allergy Clin Immunol 1999;104(3 Pt 2):S109–S113. 9. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis—Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014;71(1):116–132. 10. Eichenfield LF, Boguniewicz M, Simpson EL, et al. Translating atopic dermatitis management guidelines into practice for primary care providers. Pediatrics 2015;136(3):554–565. Published online at: www .pediatrics.org/cgi/doi/10.1542/peds.2014-3678 Accessed August 27, 2015. 11. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis—Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 2014;71:327–349. 12. van der Aa LB, Heymans HS, van Aalderen WM, Sprikkelman AB. Probiotics and prebiotics in atopic dermatitis: review of the theoretical background and clinical evidence. Pediatr Allergy Immunol 2010;21(2 Pt 2):e355–e367.