Pediatric Atopic Dermatitis

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Background

Atopic dermatitis (AD) is a chronically relapsing skin disorder with an immunologic basis.[1] The clinical presentation varies from mild to severe. In the worst cases, atopic dermatitis may interfere with normal growth and development. Treatment consists of adequate skin hydration, avoidance of allergenic precipitants, topical anti-inflammatory medications, systemic antihistamines, and antibiotic coverage of secondary infections.

Although often used interchangeably, the terms eczema and atopic dermatitis are not equivalent. Eczema is a reaction pattern with various causes and the most common pediatric cause is atopic dermatitis. Other causes of eczematous dermatitis include allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, nummular eczema, dyshidrotic eczema, asteatotic eczema, and lichen simplex chronicus. Eczematous reactions can be classified as acute, subacute, or chronic, depending on historical and physical characteristics.

The images below depict patients with atopic dermatitis.



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Typical atopic dermatitis on the face of an infant.



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Flexural involvement in childhood atopic dermatitis.

Pathophysiology

Clinically unaffected skin in patients with atopic dermatitis has increased numbers of T-helper type 2 (Th2) cells compared with skin in patients without atopic dermatitis. Increased levels of interleukin (IL)-4 and IL-13 (Th2 cytokines) are seen in acute atopic dermatitis skin lesions, whereas chronic atopic dermatitis lesions show increased expression of IL-5 (Th2 cytokine) and IL-12 and interferon (IFN)-γ (Th1 cytokines). Chronic atopic dermatitis lesions also exhibit greater eosinophil infiltration compared with skin in patients without atopic dermatitis.

IL-4 enhances differentiation of T-helper cells along the Th2 pathway, and IL-13 acts as a chemoattractant for Th2 cells to infiltrate atopic dermatitis lesions. IL-13 may also directly induce IL-5 expression and eosinophil infiltration, thereby facilitating the transition from acute lesions into chronic lesions.[2]

In addition, patients with atopic dermatitis appear to have significantly decreased levels of skin barrier molecules compared with normal controls. Ceramide lipids in the stratum corneum, which are responsible for water retention and permeability functions, and skin barrier proteins such as filaggrin are expressed at significantly lower levels in the skin of patients with atopic dermatitis compared with the skin of patients without atopic dermatitis.[2, 3]

Significant evidence favors the hygiene hypothesis for the development of atopic dermatitis. An inverse relationship is recognized between helminth infections and atopic dermatitis but no other pathogens.[4] In addition, early day care, endotoxin, unpasteurized farm milk, and animal exposure appear to be beneficial, likely because of a general increase in exposure to nonpathogenic microbes.

Positive association was shown between maternal exposure to increased concentrations of particulate matter and atopic dermatitis.[5]

Epidemiology

Frequency

United States

Atopic dermatitis occurs in approximately 10-20% of children and 2% of adults.[2] Children with concurrent asthma or hayfever have a 30-50% incidence of developing atopic dermatitis.

International

Prevalence rates for atopic dermatitis in children over a 1-year period ranged from around 2% in Iran and China to about 20% in Australasia, England, and Scandinavia.[6] Interestingly, populations that migrate from areas of low prevalence to areas of higher prevalence have shown an increased incidence of atopic dermatitis, bolstering the idea of strong environmental influences in the development of atopic dermatitis.

Race

No clear racial predilections have been identified.

Sex

Males and females are affected with equal incidence and severity.

Age

Atopic dermatitis may occur in people of any age but often starts in infants aged 2-6 months. Ninety percent of patients with atopic dermatitis experience the onset of disease prior to age 5 years.[7] Seventy-five percent of individuals experience marked improvement in the severity of their atopic dermatitis by age 14 years; however, the remaining 25% continue to have significant relapses during their adult life. A recent study concluded that the prevalence of atopic dermatitis in children younger than 2 years was 18.6%.[8]

Prognosis

Atopic dermatitis persists into adulthood in 20-40% of children with the condition. Many children outgrow severe atopic dermatitis and only experience itchy or inflamed skin if exposed to exogenous irritants as adults.

Patient Education

For excellent patient education resources, visit eMedicineHealth's Skin Conditions and Beauty Center. Also, see eMedicineHealth's patient education article Eczema.

History

Diagnostic criteria for atopic dermatitis (AD) have been proposed by Hanifin and Rajka (1980) and largely adopted by the American Academy of Allergy, Asthma, and Immunology.[9] Appropriate cases must have at least 3 major characteristics and at least 3 minor characteristics.

Major characteristics include the following:

Minor characteristics are as follows:

Most children with atopic dermatitis relate a history notable for intense pruritus and dry skin. The quality of the pruritus is referred to as a spreading itch. Affected children often have a lowered itch threshold, resulting in increased levels of cutaneous reactivity in response to stimuli. Patients may succumb to a vicious itch-scratch-itch cycle, in which pruritus stimulates a bout of scratching. This, in turn, increases skin inflammation and triggers a greater sensation of itching, thus exacerbating flares.

Altered cell-mediated immunity has been noted in patients with atopic dermatitis; these patients exhibit both impaired skin barrier function and defects in skin innate immunity.[10] This is clinically observed as a history of repeated unusual cutaneous infections (eg, eczema herpeticum, warts, molluscum, dermatophytes).[11, 12]

Physical

Th following three classes of skin lesions are recognized:

Typical locations of lesions by age are as follows:

Associated findings

Associated findings in atopic dermatitis include keratosis pilaris; accentuated palmar creases; lichenification; atopic pleats; allergic shiners; transverse nasal crease; pallor around the nose, mouth, and ears; white dermographism; cataracts; and keratoconus.

Keratosis pilaris, or plucked-chicken skin, consists of large cornified plugs in the upper part of hair follicles and produces a stippled appearance of the skin on the outer aspects of the arms and legs and on the buttocks and trunk.

Hyperlinear palms are usually present at birth and persist throughout life. These consist of an increased number of fine lines and accentuated markings on the palms.

Lichenification of the wrists, ankles, popliteal fossae, or antecubital fossae is characteristic of chronic atopic dermatitis. It is observed as thickened, leathery, hyperpigmented patches of skin with a deepening of normal skin creases. Lichenification has been studied with a statistical model.[13]

Atopic pleats (also referred to as Morgan-Dennie folds, Morgan folds, Dennie pleats, or mongolian lines) are skin folds observed just below the lower lid of both eyes and are retained throughout life.

Allergic shiners are violet-gray infraorbital discolorations caused by underlying vascular stasis. Increased pressure on nasal and paranasal venous plexuses causes edema in these areas, leading to development of atopic pleats and allergic shiners.

A prominent transverse nasal crease is a common sign of concurrent allergic rhinitis and, along with allergic shiners and atopic pleats, may be a clue to the diagnosis of an atopic diathesis.

Dermographism is a normal reaction in 5% of the population. After a firm pointed instrument is stroked against the skin, the path of the instrument is observed as a red line followed by an erythematous flare that ultimately develops into a wheal. This response occurs within 3 minutes of the insult. White dermographism is a paradoxical reaction wherein the initial red line is replaced within 10 seconds by a white line and an absence of a wheal. This reaction can be observed in atopic dermatitis and allergic contact dermatitis.

Atopic cataracts affect 4-12% of patients with AD and occur much earlier in life than senile cataracts. They typically are bilateral, central, and shield-shaped, and they mature rapidly. Because patients generally are asymptomatic, diagnosis is usually made by slit lamp examination. Incidence of cataracts in atopic patients appears to be unrelated to the use of topical steroids.

Keratoconus is an elongation of the corneal surface that is thought to be caused by long-term eye rubbing and may be a degenerative change in the cornea. Keratoconus affects approximately 1% of children with atopic dermatitis and can generally be alleviated with the use of contact lenses.

Some advocate use a scoring system, the SCORAD (Index) is the best validated scoring system in atopic dermatitis.[14, 15] The extent of disease is measured by "the rule of nines," applied on a front/back drawing of the patient's inflammatory lesions. They are graded from 0-100 on 6 items, including erythema, edema/papulation, excoriations, lichenification, oozing/crusts, and dryness, with each item evaluated on a scale from 0-3.

Causes

The etiology of atopic dermatitis appears to be linked both to genetic causes and to environmental agents.

The prevalence of atopic dermatitis in children with one affected parent is 60% and rises to nearly 80% for children of two affected parents. Additionally, nearly 40% of patients with newly diagnosed cases report a positive family history for atopic dermatitis in at least one first-degree relative. Children of parents with atopic dermatitis have an increased risk of developing atopic dermatitis by age 3 years.[16] Much higher concordance rates for atopic dermatitis are observed in monozygotic twins (77%) than in dizygotic twins (15%).[2]

Recent evidence has demonstrated a strong genetic predisposition towards the development of atopic dermatitis in patients with loss-of-function mutations in the gene that encodes the epidermal structural protein filaggrin (FLG). Filaggrin deficiency causes a significant defect in the normal epidermal barrier that allows for enhanced allergen absorption through the skin, resulting in a higher incidence of dermatitis. FLG gene mutations have been associated with a more severe atopic dermatitis phenotype, earlier onset of atopic dermatitis, increased levels of systemic allergen sensitivity, and a higher proportion of patients with atopic dermatitis who eventually develop asthma.[17]

In addition, the specific loss-of-function null mutation R501x in the filaggrin gene appears to confer a higher risk of developing eczema herpeticum, which is a rare but serious complication that requires treatment with antiviral medications.[18]

Prenatal risk factors for atopic dermatitis are under investigation. Term infants of mothers who had gestational diabetes during pregnancy had an almost 8-fold increase in the prevalence of atopic dermatitis by age 6 years. Interestingly, this relationship did not occur in preterm infants of mothers with gestational diabetes. The reasons for this discrepancy are yet to be determined.[19]

A retrospective study of 414 children and adolescents with atopic dermatitis suggested that prolonged obesity in early childhood may be a risk factor for atopic dermatitis; this advocated the concept that weight loss may facilitate prevention and treatment of childhood atopic dermatitis.[20]

Environmental allergens repeatedly have been shown to trigger exacerbations of atopic dermatitis in susceptible individuals. Contact irritants, climate, sweating, aeroallergens, microbial organisms, and stress/psyche commonly trigger exacerbations.

Contact irritants (eg, soaps, solvents, wool clothing, mechanical irritants, detergents, preservatives, perfumes) compromise the integument, creating inflammation, irritation, and a portal of entry for further environmental insult. These surface irritants, along with the macerative effects of sweating and the drying effects of low humidity, lower the pruritic threshold. A vicious cycle of itching and scratching ensues, in which added cutaneous damage caused by scratching further lowers the pruritic threshold and subsequently causes increased itching.

Aeroallergens (eg, house dust mite, molds, pollen, dander) induce peripheral eosinophilia and elevate serum IgE levels. These early effects lead to increased histamine release from IgE-activated mast cells and elevated activity of the T-helper cell–mediated immune system. The increased release of vascular mediators (eg, bradykinin, histamine, slow-reacting substance of anaphylaxis [SRS-A]) induces vasodilation, edema, and urticaria, which in turn stimulate pruritus and inflammatory cutaneous changes.

Microbial agents (eg, S aureus, Pityrosporum yeasts, Candida organisms, Trichophyton dermatophytes) act in 2 different ways to promote the flares of atopic dermatitis. The microorganisms directly invade the skin, creating local injury and inflammation, and they induce a systemic allergic response to specific antigens, causing a rise in serum IgE and enhanced activity of the immune system.

Nearly all patients with atopic dermatitis are colonized by S aureus on lesional skin. More than half of patients with atopic dermatitis are colonized by S aureus strains capable of producing superantigens. These patients can develop superantigen-specific IgE antibodies that activate inflammatory cells in the skin. Staphylococcal enterotoxin B is a superantigen known to upregulate IL-31 expression in skin. IL-31 has been shown to induce pruritus and skin lesions resembling atopic dermatitis in mice.[2] In addition, methicillin-resistant S aureus strains with reduced susceptibility to vancomycin are increasing worldwide and have been documented in atopic children.[21]

Specific IgE levels to Malassezia furfur have been correlated with atopic dermatitis severity in a subgroup of patients. These Malassezia -specific IgE antibodies have been shown to crossreact with autoantigens in atopic dermatitis skin.[2]

Food allergy is implicated as a cause in one third to one half of children with atopic dermatitis. Food allergens may be the initial trigger for IgE autoreactivity to epithelial autoantigens in young children with atopic dermatitis.[2] The most common food allergens in children are egg, soy, milk, wheat, fish, shellfish, and peanut, which together account for 90% of food-induced cases of atopic dermatitis in double-blind, placebo-controlled food challenges. Fortunately, many clinically significant food allergies self-resolve within the first 5 years of life, eliminating the need for long-term restrictive diets.

Stress may trigger atopic dermatitis at the sites of activated cutaneous nerve endings, possibly by the actions of substance P, vasoactive intestinal peptide (VIP), or via the adenyl cyclase–cyclic adenosine monophosphate (cAMP) system.

Atopic dermatitis is the result of a complex relationship between genetic predisposition and environmental exposures, including climate.[22] Atopic dermatitis prevalence was significantly lower with highest-quartile mean annual relative humidity, and with 2 other factors associated with increased UV exposure.

Laboratory Studies

No definitive laboratory tests are used to diagnose atopic dermatitis (AD). Elevated serum immunoglobulin E (IgE) levels and peripheral blood eosinophilia occur in most individuals with atopic dermatitis, and these findings may be useful in confirming the atopic status of suspected cases. The presence of serum IgE directed against the cell wall of S aureus is observed in hyper-IgE syndrome and atopic dermatitis.

Common infections that mimic or complicate atopic dermatitis can be tested for as follows: conduct a Tzanck smear for herpes simplex virus (HSV), a potassium hydroxide (KOH) preparation for dermatophytes, and a Gram stain for bacterial infections.

Other Tests

Prick skin testing to common allergens can help identify specific triggers of atopic dermatitis. For accuracy, antihistamines must be discontinued for 1 week and topical steroids for 2 weeks prior to testing. Although skin tests are used most often in young children with moderate-to-severe disease, false-negative and false-positive test results are not uncommon in children younger than 8 years. If positive, these tests do not necessarily indicate clinically significant triggers. Prick skin tests only indicate that the patient has been sensitized to particular antigens. For example, most children shown to have multiple food allergies by skin tests only demonstrate clinically detectable allergic reactions to 3 or fewer foods when tested by double-blind randomized provocative testing.

Radioallergosorbent test (RAST) and enzyme-linked immunosorbent assay (ELISA) in vitro tests identify serum IgE directed toward specific allergens (allergen-specific IgE). As with prick skin tests, these diagnostic methods show a poor predictive value for clinically significant food allergies and may produce false-positive results when the patient's serum contains elevated nonspecific (or total) IgE levels.

Histologic Findings

Acute eczematous lesions show histologic markings of hyperkeratosis, parakeratosis, and acanthosis with a decreased or absent granular cell layer.

Important features in histologic diagnosis include spongiosis (accumulation of fluid in the intercellular and intracellular areas) and exocytosis (infiltration of leukocytes through the epidermis).

Chronic eczematous lesions display hyperkeratosis with areas of parakeratosis and papillomatosis (upward proliferation of dermal papillae).

Medical Care

Rehydration

The most fundamental and important step in combating atopic dermatitis (AD) is rehydration of the stratum corneum. Adequate rehydration preserves the stratum corneum barrier, minimizing the direct effects of irritants and allergens on the skin and maximizing the effect of topically applied therapies, thus decreasing the need for topical steroids.

Lukewarm soaking baths lasting 10-20 minutes are ideal.[7] Extremely hot water should be avoided to prevent both vasodilation, which can trigger pruritus, and the damage to the skin barrier caused by scalding.

Small amounts of bath oils or emulsification agents may be used for added hydration benefits in older children and adolescents. Bath oils or emulsification agents result in slippery conditions; warn patients and parents of the resultant risks of trauma and drowning after a fall. Readily available over-the-counter bath agents include Aveeno Colloid Oatmeal, RoBathol, Maypo, cottonseed oil with Brij 93, or mineral oil.

Recommended soaps are mild and unscented with a neutral pH. Examples include Dove, Oil of Olay, Caress, Camay, Aveeno, and Purpose. Even these mild soaps are often too drying for atopic skin. If the children are prepubertal, bathing in water alone may be preferable. Postpubertal patients need to use soap in the axillae and groin but do not need it elsewhere.

If soaps are too irritating to the skin, hydrophobic lotions and creams, such as Cetaphil, Diprobase, and Unguentum Merck, may be used. These agents have excellent cleansing properties and low potential for irritation. They should be applied without water and rubbed gently over the skin surface until a light foaming occurs. A soft cotton cloth or tissue can then be applied to wipe away the agent, leaving behind a protective film of stearyl alcohol and propylene glycol.

Baby shampoo may be used to manage scalp dermatitis.

Emollients

Baths should be followed by the immediate application of an occlusive emollient over the entire skin surface to retain moisture in the epidermis. If an emollient is not applied within 3 minutes of leaving the bath, evaporation causes excess drying of the skin. Skin should not be completely dried with a towel prior to application of the emollient; rather, lightly patting the skin with a towel to remove excess moisture is sufficient.

Frequently recommended emollients are hydrophobic and ointment-based; these include Vaseline petrolatum jelly, Crisco, vegetable oil, Aquaphor, and Elta. Occasionally, parents may find these agents too greasy for everyday use, and cream-based alternatives may be offered. Common creams include DML Forte, Moisturel, Aveeno, Curel, Purpose, Dermasil, Neutrogena, and Eucerin. This latter group of moisturizers is less effective because of the weaker occlusive effects of creams as compared to ointments; thus, they should be used only if the ointment-based emollients are not well tolerated.

The newest type of moisturizing product is a ceramide-dominant, lipid-based emollient (TriCeram) aimed at repairing the stratum corneum barrier function lost in atopic dermatitis. One study showed a significant decrease in clinical severity scores and a decrease in transepidermal water loss in children whose traditional moisturizers were replaced by TriCeram for 3 weeks.[23]

Urea-containing products have been shown to soften and moisturize dry skin. Commonly available preparations include Aquacare cream or lotion and Ureacin Crème. Alpha-hydroxy and lactic acid preparations also are helpful as moisturizers. Name brands include Aqua Lacten Lotion, AmLactin Lotion, LactiCare Lotion, Lac-Hydrin Lotion, and Nutraderm 30. In addition, 12% ammonium lactate lotion has been shown to improve skin barrier function and even to mitigate dermal or epidermal atrophy induced by corticosteroids.[23] Because of the stinging sensation experienced by children with acute or fissured dermatoses, the 10% urea concentration is preferred over the higher concentrations, and care should also be used in the application of the alpha-hydroxy and lactic acid preparations. LactiCare-HC Lotion also contains hydrocortisone to further benefit acute flares of atopic dermatitis.

For children with repeated cutaneous infections, adding 2 teaspoons of household bleach (eg, Clorox) per gallon of bath water can help reduce the incidence of such infections. A typical bathtub holds approximately 25-40 gallons of water. During acute atopic dermatitis exacerbations, pouring 1 cup of table salt into the bath may ameliorate the stinging effect these children frequently experience while bathing.

Wet dressings are very useful for diverse types of atopic dermatitic flares and severe recalcitrant atopic dermatitis.[24] They can be used on dry lichenified lesions to improve hydration and increase the penetration of topical corticosteroids; they also work well to dry weeping or oozing lesions via evaporation. The cooling sensation on the skin that results from slow evaporation with wet dressings has an anti-inflammatory effect and suppresses itching. The mechanical barrier of the wet dressing also prevents scratching, allows more rapid healing of lesions, and offers protection from contact with allergens and bacteria. Care should be taken to use only adequately diluted corticosteroid preparations (if used) under occlusive dressings to prevent hypothalamic-pituitary-adrenal axis suppression and local adverse effects on the skin. Wet wrap implementation should be delayed at least 2-3 days after beginning antibiotic treatment for superinfected lesions to allow for observation of clinical improvement of infected sores.[3]

Burow solution 1:40 is a commonly used wet dressing because it is germicidal and directly suppresses weeping lesions by precipitation of protein. The solution is prepared easily by dissolving one Domeboro packet or effervescent tablet in a pint of tepid or lukewarm tap water. Using lukewarm water is essential because hot water induces vasodilatation with increased weeping and pruritus, whereas cold water causes vasoconstriction and secondary vasodilation. Submerge a soft cloth (eg, handkerchief, thin diaper, strips of bed sheets) into the solution until moderately wet but not dripping. Place the dressing over the affected skin site, periodically rewetting the compress. In severe cases, a topical corticosteroid may be applied after the compress for enhanced penetration and action of the medication.

Seek psychologic counseling, biofeedback, relaxation techniques, massage therapy, and behavioral modifications if emotional stressors are a contributing factor to atopic dermatitis.

Ultraviolet light

Ultraviolet light may benefit some patients.

Ultraviolet light in the UVB range may provide control and eliminate or markedly reduce the need for steroids. The new narrow band units are especially effective. Ultraviolet light in the UVA range has been used alone, in combination with oral psoralen administration (PUVA), or with high-dose UVA 1 (ie, 340-400 nm spectrum units).

A significant decline in the usage of UVA light therapy and psoralen has been recently observed because this regimen clearly accelerates photoaging and increases the risk of skin cancer. UVA 1 spectrum light works by reducing cellular immunoglobulin E (IgE) binding sites and inducing apoptosis in inflammatory cells and has demonstrated significant efficacy in treating atopic dermatitis. A small number of patients develop erythema or disease flares with light treatment.

Allergen immunotherapy

Allergen immunotherapy is currently indicated only for patients with allergic rhinitis or allergic asthma. However, several small randomized controlled trials have shown a significant clinical benefit of subcutaneous immunotherapy or sublingual immunotherapy with house dust mite extract in patients sensitized to the house dust mite. Larger randomized, double-blind, placebo-controlled trials are needed to confirm these findings.[25]

Consultations

Consider consultation with an allergist/immunologist or dermatologist for the following conditions:

Diet

Whether breastfeeding can help prevent development of atopic dermatitis in children remains unclear. A clinical report from the American Academy of Pediatrics recommended exclusive breastfeeding as opposed to cow's milk formula feeding over the first 4 months of life to prevent development of atopic dermatitis in infants at high risk of developing atopy.[26] However, several studies have found no protective benefit of exclusive breastfeeding in the first 3-6 months of life.[27, 28]

Supplementation with extensively hydrolyzed formulas in infants at high risk of developing atopic dermatitis appeared to be more effective at preventing atopic dermatitis than supplementation with partially hydrolyzed formulas or cow's milk formulas.[26] However, partially hydrolyzed cow's milk formula may be beneficial in treating infants with mild-to-moderate atopic dermatitis during the first 6 months of their life without affecting their nutritional status.[29]

For children older than 5 years, nutritionally adequate elimination diets are the goal if double-blind placebo-controlled trials indicate a clinically significant food allergy. However, most skin tests, radioallergosorbent tests (RASTs), and enzyme-linked immunosorbent assays (ELISA) that reveal positive results against food allergens are not borne out to cause disease flares in clinical trials; thus, elimination diets are only rarely indicated.

Activity

Prohibit smoking in the home and in other areas that are frequented by children with allergies.

Implement dust mite control measures for children with documented sensitivity to dust mites. Counsel parents to use dust mite–proof plastic cases around pillows, mattresses, and box springs. Wash bedding in hot water weekly to remove dust mites. Remove carpets and drapes from the bedroom or vacuum carpets and drapes weekly to remove dust mites.

In the subgroup of children with atopic dermatitis who also experience respiratory allergies to animal allergens, parents should consider removing animals from the home or confining them to areas of the house where susceptible children do not come into contact with their dander or saliva.

Avoid irritants that trigger the itch-scratch-itch cycle (eg, soaps, detergents, chemicals, abrasive clothing, extremes of temperature and humidity).

Use pH-neutral minimally defatting soaps (eg, Dove). Avoid excessive drying of the skin with alcohol-containing astringents. Launder new clothes before wearing to remove manufacturing chemicals. Use liquid detergent rather than powder detergent and add a second rinse cycle to remove all residual detergent.

Wear loose fitting open-weave cotton or cotton-blend clothing; avoid wool.

Use a humidifier in the winter to prevent excessive skin dryness and an air conditioner in the summer to prevent sweating and associated macerative effects on the skin. Decreased humidity indoors helps prevent the growth of mold.

Complications

The most common complication of atopic dermatitis is secondary infection.

Staphylococcus species and group A beta-hemolytic streptococci are the most frequent organisms cultured from skin lesions. Superinfected eczematoid lesions appear as erythema associated with serous or purulent exudates and crusting. Greasy moist scales on the surface of the lesions and small pustules at the advancing edges may be present. Always consider infection in acute flares of chronic atopic dermatitis or in cases that are unresponsive to appropriate therapy.

Topical antibiotic therapy is useful for localized infections; however, systemic treatment is preferred for recurrent or widespread infections. The agent of choice is penicillin G if group A streptococci is the known infectious organism. Use erythromycin or a semisynthetic penicillin (eg, nafcillin, oxacillin, dicloxacillin) if S aureus is a possible cause. Hospitalization and use of intravenous antibiotics are indicated in cases of invasive infection (eg, osteomyelitis). Perform urinalysis and closely observe patients for symptoms for at least 7 weeks after treatment in endemic areas because systemic antibiotic treatment does not prevent postinfectious glomerulonephritis after a cutaneous infection with nephritogenic M strains of streptococci.

Less commonly, patients with atopic dermatitis may develop an explosive vesicular eruption known as Kaposi varicelliform eruption or eczema herpeticum. Vesicles and pustules are typically umbilicated and are initially confined to eczematous skin but may later spread to normal skin. Later in the course of the disease, erosions may be commonplace and confluent, resulting in denuded areas. Tzanck smear of vesicles or a viral culture confirms the diagnosis. Treatment is with acyclovir (if mild, administer 25-30 mg/kg/d, up to 200 mg 5 times per day orally; if severe, administer 5 mg/kg/dose every 8 h or 1.5 g/m2/d intravenously).

Atopic dermatitis nearly doubles an individual's risk of developing lymphoma. This risk increases with usage of potent topical steroids, especially for prolonged time periods.[30]

Sleep disturbances are common in those with atopic dermatitis.[31] They have reduced sleep efficiency, longer sleep onset latency, more sleep fragmentation, and less nonrapid eye movement sleep. Reduced nocturnal melatonin secretion may be linked.

Prevention

Prevention of acute flares and the subsequent development of chronic lesions of atopic dermatitis are indicators of successful treatment for this disease. Maintenance of adequate hydration of the stratum corneum, avoidance of known or probable allergens and irritants, rapid self-treatment with the proper class of topical steroids, and judicious use of complementary therapies (eg, antipruritics, stress relievers, antibiotics) are the cornerstones of ensuring a high quality of life unimpeded by the more severe aspects of this disease.

Nonspecific triggers of inflammation in patients with atopic dermatitis may include physical or chemical irritants. The following simple measures should be followed in daily life to reduce the frequency and severity of irritant-induced atopic dermatitis flares[32] :

Prenatal and postnatal probiotic supplementation may be helpful in preventing the development of atopic dermatitis in young children. In a recent meta-analysis, the most commonly studied probiotic was Lactobacillus rhamnosus GG.[33] Larger, randomized controlled studies are needed to confirm these initial findings.

A dog living in the home at the time of birth has been associated with a 50% decrease in the incidence of atopic dermatitis at age 3 years.[16] One study found that, at age 4 years, dog-sensitized children experienced less risk for eczema, whereas cat sensitization significantly increased the risk.[34]

Children with ichthyosis vulgaris should avoid neonatal cat exposure to prevent atopic dermatitis.[35]

Breastfeeding during the first 4 months of life may reduce in incidence and severity of childhood atopic disease but only modestly and only in those at high risk.[36]

Long-Term Monitoring

Frequent follow-up is needed early in the course of atopic dermatitis (AD) to ensure compliance and assess patient responsiveness to therapy. Analyze treatment failures for the presence of resistant organisms, contact dermatitis to a medication (eg, preservatives in steroid preparations, bacitracin), or parental noncompliance.

Medication Summary

Topical corticosteroids are the mainstay of treatment of atopic dermatitis (AD).[37] These medications reduce inflammation and pruritus primarily by inhibiting the transcriptional activity of various proinflammatory genes. Topical steroids should be applied only to areas of acute exacerbations, whereas emollients should be used over the remainder of the skin. The absorption of topical steroids is much better through hydrated skin; thus, the ideal time for application is in the first 3 minutes after a bath or shower. The various topical steroid formulations, in ascending order of occlusiveness, include lotions, creams, gels, and ointments. The proactive wet-wrap method with diluted corticosteroids has been advocated.[38]

A new topical 2% ointment, crisaborole, a phosphodiesterase 4 inhibitor, has shown promise for children and adolescents with atopic dermatitis.[39] This boron-based phosphodiesterase-4 inhibitor may prove a good choice for twice-daily use in mild-to-moderate atopic dermatitis.[40] It reduces the dermatitis and associated pruritus without apparent undesirable side effects.

Lotions contain water and may be drying because of the evaporative effect; thus, they are used mostly in scalp and beard areas where drying effects are not as problematic. Lotions containing alcohol may cause a burning sensation upon application, especially on skin with fissured or ulcerated areas. Lotions may contain preservatives, solubilizers, and fragrances that can irritate the skin.

Creams are generally well tolerated but are less moisturizing than ointments. Creams are popular for their nongreasy appearance on treated skin and are more convenient during hot weather because they cause less occlusion of eccrine sweat glands than ointments and gels. As with lotions, creams may contain preservatives, solubilizers, and fragrances that can irritate the skin.

Gels are highly occlusive, but the propylene glycol base is irritating to the skin and promotes dryness. Therefore, gels, similar to lotions, are used mostly in scalp and beard areas where the drying effects are not as problematic. They are very effective in the management of acute weeping or vesicular lesions of atopic dermatitis.

Ointments are the most moisturizing of the topical steroid vehicles, but their occlusiveness may not be well tolerated because of their interference with sweat gland function and resultant development of sweat retention dermatitis, especially in warm humid climates. Ointments are the preferred vehicle for thickened, lichenified plaques of atopic dermatitis.

Systemic corticosteroids have been used in severe chronic atopic dermatitis, but use has been limited in the pediatric population because of the risk of severe adverse effects associated with chronic usage, including growth retardation and immune suppression.

Oral antihistamines are effective as systemic antipruritics, sedatives, and mild anxiolytics. These are beneficial especially at nighttime because pruritus is usually worse at night. Commonly used oral antihistamines include diphenhydramine, hydroxyzine, and doxepin. Pramoxine is a topical antipruritic agent and can be found as Prax, Pramosone, or PrameGel.

Coal tar topical preparations have antipruritic and anti-inflammatory effects.[41] They work as disinfectants and astringents and help to correct abnormal keratinization by decreasing both epidermal proliferation and dermal infiltration. They are effective as second-line agents for subacute, chronic, and lichenified atopic dermatitis. Cosmetically acceptable preparations recently have been made available and include AquaTar, Estar, Fototar, PsoriGel, and Neutrogena T/Derm Tar Emollient. Tar shampoos, such as Neutrogena T-Gel, are effective for scalp involvement. Adverse effects may include folliculitis and photosensitivity.

Topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus) are the newest class of topical medications for atopic dermatitis. These nonsteroidal immunomodulators act by down-regulating the mediator release or cytokine expression of various cells, including Th1 helper cells, Th2 helper cells, mast cells, eosinophils, keratinocytes, and Langerhans cells. Calcineurin inhibitors may be especially useful for treating face, groin, or axillary areas, where steroid-sparing treatments are preferred. The safety of pimecrolimus has been stressed for infants and other children, with the conclusion made that labeling restrictions be lifted.[42]  Calcineurin inhibitors and corticosteroids have similar benefit, but the former is more expensive and may produce skin burning and pruritus.[37]

Several studies have documented the rapid and prolonged improvement in clinical severity scores in children and adults with a range of severity of atopic dermatitis treat with topical calcineurin inhibitors. Research has shown the beneficial effect of topical calcineurin inhibitors in patients refractory to topical corticosteroid therapy.[43, 44] The most common adverse effect is a local burning sensation upon application, but this symptom tends to diminish after the first few days of use.

In January 2006, the Food and Drug Administration (FDA) approved a black box warning for tacrolimus and pimecrolimus topical medications. The warning emphasized the lack of long-term safety data and a possible link to malignancies. No causal link between these agents and the development of malignancies has been established. Long-term studies on the safety of these agents in humans are not yet available, and the black box warning was based on case reports in humans and on animal studies. An analysis of tacrolimus ointment use in patients with atopic dermatitis over 4 years did not show any increased risk of infections or cancer.[45] However, longer term studies (10 y of follow-up or longer) are needed before firm conclusions about these concerns can be reached. The safety of pimecrolimus has been stressed; labeling restrictions may be unnecessary.[42]

Establishing the long-term safety profile of topical calcineurin inhibitors is of paramount importance because they appear to provide an effective alternative to topical corticosteroid treatment in certain patients. Furthermore, pimecrolimus has been shown to improve the epidermal skin barrier without the concurrent risk of local skin atrophy commonly seen with topical corticosteroid treatment.[46] Thus, pimecrolimus appears to be an attractive candidate for long-term use in either a therapeutic or preventative capacity.

At the present time, physicians are advised to use the following guidelines when prescribing topical immunomodulators such as tacrolimus and pimecrolimus[47, 48] :

Oral cyclosporine has proven beneficial in patients with severe atopic dermatitis refractory to treatment with topical steroids. Discontinuation of cyclosporine frequently results in rapid relapse of skin disease. Significant adverse effects (eg, nausea, abdominal discomfort, hypertrichosis, paresthesias, hypertension, hyperbilirubinemia, renal impairment) have diminished enthusiasm for this drug, especially with the advent of the topical immunomodulators mentioned above.

Experimental treatments for atopic dermatitis have included trials of gamma-interferon and IL-2; both are inhibitors of Th2 cell functions and have been promising. Oral mycophenolate mofetil, an inhibitor of purine synthesis, has also been shown to be an effective alternative form of treatment for severe disease. A small study of 6 patients with severe atopic dermatitis showed promising results for treatment with anti-CD20 monoclonal antibody (Rituximab).[49]

Some evidence suggests that the use of traditional Chinese medicine herb combinations may result in short-term improvements in SCORing of Atopic Dermatitis (SCORAD) index scores, quality of life scores, and topical steroid use.[50] However, larger trials to evaluate safety and long-term efficacy are needed.

Conflicting results have been reported regarding the use of probiotics (eg, Lactobacillus, Bifidobacterium) in preventing atopic dermatitis or in controlling symptoms in children.[50] A recent meta-analysis indicated that prenatal and postnatal probiotic supplementation may be helpful in preventing the development of atopic dermatitis in young children but does not appear to be effective in treating existing atopic dermatitis.[33] Further studies on the subject are needed prior to developing firm conclusions on the usefulness of this complementary medicinal treatment. Deo et al have suggested low-dose methotrexate as a treatment option in the pediatric population.[51]

Hydrocortisone topical (Cortizone, Dermolate, Westcort)

Clinical Context:  Hydrocortisone topical is an adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. It has mineralocorticoid and glucocorticoid effects, resulting in anti-inflammatory activity.

Triamcinolone topical (Kenalog)

Clinical Context:  It treats inflammatory dermatosis that is responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.

Flurandrenolide (Cordran Tape)

Clinical Context:  Flurandrenolide is an intermediate-potency topical corticosteroid. Each square cm provides 4 mcg.

Class Summary

In older children and adolescents, treat mild cases of atopic dermatitis with a low-potency (class VI or VII) topical steroid twice a day to decrease inflammation. Examples include hydrocortisone cream or ointment, 1% and 2.5%. For moderate cases of atopic dermatitis, intermediate-potency steroids (class III, IV, V) may be used for brief periods (< 2 wk) to control an eczematous flare. Subsequently, low-potency steroids can be used to maintain remission. For severe cases of atopic dermatitis, pulse therapy with high-potency topical steroids (class II) or oral steroids may be beneficial in adolescents. Use only low-potency steroids on the face, axillae, groin, and intertriginous areas because of increased absorption and increased local steroid adverse effects.

For mild atopic dermatitis in infants, class VI or VII topical steroids should be effective. If the infant has more severe atopic dermatitis, a moderate-potency steroid can be prescribed for as long as 1 week and then tapered down to a lower-potency medication for maintenance therapy. In general, do not treat infants with topical steroids in the high-potency classes (class II or above) without a referral to a dermatologist.

Cordran tape is a corticosteroid-impregnated polyethylene film that enhances topical steroid penetration up to 100-fold. Occlusion of a topical steroid under plastic wrap seems to work equally well. These methods are especially useful for chronic lichenified plaques of atopic dermatitis.

In order to achieve a quick, complete remission of atopic dermatitis symptoms, adequate amounts of topical steroid must be used. Many patients initially use suboptimal amounts of topical steroid products, leading to poor control of their atopic dermatitis symptoms and ultimate discontinuation of their therapy. Approximately 30 grams of medication is needed to cover the entire surface area of an adult body. For children, the fingertip unit (FTU) has been shown to accurately measure an appropriate amount of medication. The FTU is defined as the amount of topical medication that will cover the child's index finger from the tip to the metacarpophalangeal joint. For topical steroids, 1 FTU covers the hand or groin, 2 FTUs cover the face or foot, 3 FTUs cover an arm, 6 FTUs cover a leg, and 14 FTUs cover the trunk.

Atopic dermatitis increases the risk of developing lymphoma (both Hodgkin disease and non-Hodgkin lymphoma). This risk correlates with increasing severity of disease. An even higher risk of lymphoma occurs in patients with atopic dermatitis treated with topical corticosteroids. The risk reportedly rose with increasing potency of the topical corticosteroid and with longer duration of use.

Prednisone (Deltasone, Orasone)

Clinical Context:  Prednisone decreases inflammation by reversing increased capillary permeability and suppressing PMN activity.

Class Summary

Symptoms typically dramatically improve in the first few days of treatment with systemic steroids, only to be followed by an equally dramatic rebound flare after cessation of treatment. Tapering oral steroids over 10-14 days may mitigate this effect. In addition, an intensified focus on hydration with bathing and appropriate use of topical steroids should be emphasized to prevent rebound phenomena after discontinuation of systemic steroids.

Mupirocin topical cream or ointment (Bactroban)

Clinical Context:  Mupirocin topical cream or ointment inhibits bacterial growth by inhibiting RNA and protein synthesis.

Cephalexin (Keflex, Keftab)

Clinical Context:  Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms. Its primary activity is against skin flora.

Erythromycin (E.E.S., Erythrocin) or azithromycin (Zithromax)

Clinical Context:  Erythromycin is a macrolide antibiotic that inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.

Oxacillin (Bactocill)

Clinical Context:  Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci and may be used to initiate therapy when a staphylococcal infection is suspected.

Amoxicillin and clavulanate (Augmentin)

Clinical Context:  This drug combination treats bacteria resistant to beta-lactam antibiotics. Base dosage regimen on amoxicillin content. Because of different amoxicillin-clavulanic acid ratios in the 250-mg tablet (250/125) versus the 250-mg chewable tablet (250/62.5), do not use the 250-mg tablete until the child weighs more than 40 kg.

Acyclovir (Zovirax)

Clinical Context:  Patients experience less pain and faster resolution of cutaneous lesions when used within 48 hours of rash onset. Acyclovir may prevent recurrent outbreaks.

Ketoconazole (Nizoral)

Clinical Context:  Ketoconazole is an imidazole broad-spectrum antifungal agent. It inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Dicloxacillin

Clinical Context:  Dicloxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci and may be used to initiate therapy when a staphylococcal infection is suspected.

Class Summary

Antistaphylococcal antibiotics (eg, topical mupirocin or bacitracin, first-generation cephalosporins, macrolides, penicillinase-resistant extended-spectrum penicillins such as oxacillin or dicloxacillin if resistant strains of S aureus are encountered, amoxicillin-clavulanate) are helpful in secondary bacterial infections. Herpes simplex superinfections (eczema herpeticum) should be suspected if vesicles are present or if no improvement is observed with oral antibiotics. Tzanck smear of the base of vesicles is positive in 70% of cases. Treat with oral or intravenous acyclovir for 10 days. Varicella infections may become severe in the setting of atopic dermatitis, and early treatment with acyclovir is recommended. Counsel all children with atopic dermatitis as to the benefits of vaccination against varicella. Treat dermatophyte infections with topical or oral antifungals, such as topical ketoconazole cream or shampoo.

Pramoxine topical (Azo Itch Relief Maximum Strength Analgesic Cream, Eczemin, Itch-X Gel)

Clinical Context:  Pramoxine elicits anesthetic effect by blocking nerve conduction and impulses by inhibiting depolarization of neurons.

Doxepin cream (Prudoxin, Xepin, Zonalon)

Clinical Context:  Doxepin topical cream is a potent antihistamine and is indicated for pruritus.

Diphenhydramine (Alka-Seltzer Plus Allergy, Benadryl, Benadryl Allergy Dye-Free LiquiGels)

Clinical Context:  Diphenhydramine can be used for symptomatic relief of symptoms caused by the release of histamine in allergic reactions.

Hydroxyzine (Vistaril)

Clinical Context:  Hydroxyzine can be used for symptomatic relief of symptoms caused by the release of histamine in allergic reactions.

Doxepin (Silenor)

Clinical Context:  Doxepin can be used for symptomatic relief of symptoms caused by the release of histamine in allergic reactions.

Class Summary

Topical local anesthetics or antihistamines (topical or systemic) may be used to decrease pruritus.

Tacrolimus, topical (Protopic)

Clinical Context:  The mechanism of action of tacrolimus in atopic dermatitis is not known. This agent reduces itching and inflammation by suppressing the release of cytokines from T cells. It also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-α, all of which are involved in the early stages of T-cell activation. Additionally, this agent may inhibit the release of preformed mediators from skin mast cells and basophils, and it may down-regulate the expression of FCeRI on Langerhans cells. It is used for the short-term or intermittent long-term treatment of moderate-to-severe atopic dermatitis that is unresponsive to first-line therapies (eg, topical corticosteroids) or in cases in which first-line therapies are not applicable. The manufacturer and FDA recommend that the smallest amount and lowest potency that is efficacious be used to achieve control of symptoms. It is available as an ointment in concentrations of 0.03% and 0.1%.

Pimecrolimus (Elidel cream)

Clinical Context:  Pimecrolimus is the first nonsteroid cream approved in the US for mild-to-moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by the fungus Streptomyces hygroscopicus var. ascomyceticus. This agent selectively inhibits production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy was not observed in clinical trials, a potential advantage over topical corticosteroids. This agent is indicated only after other treatment options have failed. Pimecrolimus is available as a 1% cream.

Cyclosporine (Sandimmune, Neoral)

Clinical Context:  Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions.

Class Summary

Topical tacrolimus ointment and pimecrolimus cream have both been shown to diminish pruritus and inflammation markedly within 3 days of initiating therapy and to have persistent effects for as long as 12 months.

Author

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Disclosure: Nothing to disclose.

Specialty Editors

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Caroline C Spagnola, MD, to the development and writing of this article.

References

  1. Turner JD, Schwartz RA. Atopic dermatitis. A clinical challenge. Acta Dermatovenerol Alp Panonica Adriat. 2006 Jun. 15(2):59-68. [View Abstract]
  2. Ong PY, Leung DY. Immune dysregulation in atopic dermatitis. Curr Allergy Asthma Rep. 2006 Sep. 6(5):384-9. [View Abstract]
  3. Oranje AP, Devillers AC, Kunz B, et al. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel's opinion and review of the literature. J Eur Acad Dermatol Venereol. 2006 Nov. 20(10):1277-86. [View Abstract]
  4. Flohr C, Yeo L. Atopic dermatitis and the hygiene hypothesis revisited. Curr Probl Dermatol. 2011. 41:1-34. [View Abstract]
  5. Stelmach I, Bobrowska-Korzeniowska M, Smejda K, Majak P, Jerzynska J, Stelmach W, et al. Risk factors for the development of atopic dermatitis and early wheeze. Allergy Asthma Proc. 2014 Sep. 35(5):382-389. [View Abstract]
  6. Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR,. Is eczema really on the increase worldwide?. J Allergy Clin Immunol. 2008 Apr. 121(4):947-54.e15. [View Abstract]
  7. Ong PY, Boguniewicz M. Atopic dermatitis. Prim Care. 2008 Mar. 35(1):105-17, vii. [View Abstract]
  8. Kvenshagen B, Jacobsen M, Halvorsen R. Atopic dermatitis in premature and term children. Arch Dis Child. 2009 Mar. 94(3):202-5. [View Abstract]
  9. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venreol. 1980. 92:44-7.
  10. Mrabet-Dahbi S, Maurer M. Innate immunity in atopic dermatitis. Curr Probl Dermatol. 2011. 41:104-11. [View Abstract]
  11. Lee R, Schwartz RA. Pediatric molluscum contagiosum: reflections on the last challenging poxvirus infection, Part 2. Cutis. 2010 Dec. 86(6):287-92. [View Abstract]
  12. Lee R, Schwartz RA. Pediatric molluscum contagiosum: reflections on the last challenging poxvirus infection, Part 1. Cutis. 2010 Nov. 86(5):230-6. [View Abstract]
  13. Glazenburg EJ, Mulder PG, Oranje AP. A statistical model to predict the reduction of lichenification in atopic dermatitis. Acta Derm Venereol. 2015 Mar. 95 (3):294-7. [View Abstract]
  14. Oranje AP. Practical Issues on Interpretation of Scoring Atopic Dermatitis: SCORAD Index, Objective SCORAD, Patient-Oriented SCORAD and Three-Item Severity Score. Curr Probl Dermatol. 2011. 41:149-55. [View Abstract]
  15. van Oosterhout M, Janmohamed SR, Spierings M, Hiddinga J, de Waard-van der Spek FB, Oranje AP. Correlation between Objective SCORAD and Three-Item Severity Score used by physicians and Objective PO-SCORAD used by parents/patients in children with atopic dermatitis. Dermatology. 2015. 230 (2):105-12. [View Abstract]
  16. Bisgaard H, Halkjaer LB, Hinge R, et al. Risk analysis of early childhood eczema. J Allergy Clin Immunol. 2009 Jun. 123(6):1355-60.e5. [View Abstract]
  17. Leung DY. Our evolving understanding of the functional role of filaggrin in atopic dermatitis. J Allergy Clin Immunol. 2009 Sep. 124(3):494-5. [View Abstract]
  18. Gao PS, Rafaels NM, Hand T, et al. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum. J Allergy Clin Immunol. 2009 Sep. 124(3):507-13, 513.e1-7. [View Abstract]
  19. Kumar R, Ouyang F, Story RE, et al. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood. J Allergy Clin Immunol. 2009 Nov. 124(5):1031-8.e1-4. [View Abstract]
  20. Silverberg JI, Kleiman E, Lev-Tov H, et al. Association between obesity and atopic dermatitis in childhood: A case-control study. J Allergy Clin Immunol. 2011 May. 127(5):1180-1186.e1. [View Abstract]
  21. Alzolibani AA, Al Robaee AA, Al Shobaili HA, Bilal JA, Issa Ahmad M, Bin Saif G. Documentation of vancomycin-resistant Staphylococcus aureus (VRSA) among children with atopic dermatitis in the Qassim region, Saudi Arabia. Acta Dermatovenerol Alp Panonica Adriat. 2012 Sep. 21(3):51-3. [View Abstract]
  22. Silverberg JI, Hanifin J, Simpson EL. Climatic factors are associated with childhood eczema prevalence in US. J Invest Dermatol. 2013 Jan 18. [View Abstract]
  23. Chamlin SL, Kao J, Frieden IJ, et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002 Aug. 47(2):198-208. [View Abstract]
  24. Leloup P, Stalder JF, Barbarot S. Outpatient Home-based Wet Wrap Dressings with Topical Steroids with Children with Severe Recalcitrant Atopic Dermatitis: A Feasibility Pilot Study. Pediatr Dermatol. 2015 Apr 22. [View Abstract]
  25. Novak N. Allergen specific immunotherapy for atopic dermatitis. Curr Opin Allergy Clin Immunol. 2007 Dec. 7(6):542-46. [View Abstract]
  26. [Guideline] Greer FR, Sicherer SH, Burks AW. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics. 2008 Jan. 121(1):183-91. [View Abstract]
  27. Yang YW, Tsai CL, Lu CY. Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies. Br J Dermatol. 2009 Aug. 161(2):373-83. [View Abstract]
  28. Miyake Y, Tanaka K, Sasaki S, et al. Breastfeeding and atopic eczema in Japanese infants: The Osaka Maternal and Child Health Study. Pediatric Allergy & Immunology. May 2009. 20:234-241. [View Abstract]
  29. Jin YY, Cao RM, Chen J, Kaku Y, Wu J, Cheng Y, et al. Partially hydrolyzed cow's milk formula has a therapeutic effect on the infants with mild to moderate atopic dermatitis: a randomized, double-blind study. Pediatr Allergy Immunol. 2011 May 4. [View Abstract]
  30. Arellano FM, Arana A, Wentworth CE, et al. Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom. J Allergy Clin Immunol. 2009 May. 123(5):1111-6, 116.e1-13. [View Abstract]
  31. Chang YS, Chou YT, Lee JH, Lee PL, Dai YS, Sun C, et al. Atopic dermatitis, melatonin, and sleep disturbance. Pediatrics. 2014 Aug. 134(2):e397-405. [View Abstract]
  32. Boguniewicz M. Topical treatment of atopic dermatitis. Immunol Allergy Clin North Am. 2004 Nov. 24(4):631-44, vi-vii. [View Abstract]
  33. Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol. 2008 Jan. 121(1):116-121.e11. [View Abstract]
  34. Epstein TG, Bernstein DI, Levin L, Khurana Hershey GK, Ryan PH, Reponen T, et al. Opposing effects of cat and dog ownership and allergic sensitization on eczema in an atopic birth cohort. J Pediatr. 2011 Feb. 158(2):265-71.e1-5. [View Abstract]
  35. Thyssen JP, Godoy-Gijon E, Elias PM. Ichthyosis vulgaris - the filaggrin mutation disease. Br J Dermatol. 2013 Jan 10. [View Abstract]
  36. Blattner CM, Murase JE. A practice gap in pediatric dermatology: does breast-feeding prevent the development of infantile atopic dermatitis?. J Am Acad Dermatol. 2014 Aug. 71(2):405-6. [View Abstract]
  37. Broeders JA, Ahmed Ali U, Fischer G. Systematic review and meta-analysis of randomized clinical trials (RCTs) comparing topical calcineurin inhibitors with topical corticosteroids for atopic dermatitis: A 15-year experience. J Am Acad Dermatol. 2016 May 11. [View Abstract]
  38. Janmohamed SR, Oranje AP, Devillers AC, Rizopoulos D, van Praag MC, Van Gysel D, et al. The proactive wet-wrap method with diluted corticosteroids versus emollients in children with atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2014 Jun. 70(6):1076-82. [View Abstract]
  39. Jarnagin K, Chanda S, Coronado D, Ciaravino V, Zane LT, Guttman-Yassky E, et al. Crisaborole Topical Ointment, 2%: A Nonsteroidal, Topical, Anti-Inflammatory Phosphodiesterase 4 Inhibitor in Clinical Development for the Treatment of Atopic Dermatitis. J Drugs Dermatol. 2016 Apr 1. 15 (4):390-6. [View Abstract]
  40. Draelos ZD, Stein Gold LF, Murrell DF, Hughes MH, Zane LT. Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies. J Drugs Dermatol. 2016 Feb 1. 15 (2):172-6. [View Abstract]
  41. Paghdal KV, Schwartz RA. Topical tar: back to the future. J Am Acad Dermatol. 2009 Aug. 61(2):294-302. [View Abstract]
  42. Luger T, Boguniewicz M, Carr W, et al. Pimecrolimus in atopic dermatitis: Consensus on safety and the need to allow use in infants. Pediatr Allergy Immunol. 2015 Jun. 26 (4):306-15. [View Abstract]
  43. Leung DY, Hanifin JM, Pariser DM, et al. Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial. Br J Dermatol. 2009 Aug. 161(2):435-43. [View Abstract]
  44. Doss N, Reitamo S, Dubertret L, et al. Superiority of tacrolimus 0.1% ointment compared with fluticasone 0.005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial. Br J Dermatol. 2009 Aug. 161(2):427-34. [View Abstract]
  45. Remitz A, Reitamo S. Long-term safety of tacrolimus ointment in atopic dermatitis. Expert Opin Drug Saf. 2009 Jul. 8(4):501-6. [View Abstract]
  46. Jensen JM, Pfeiffer S, Witt M, et al. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol. 2009 May. 123(5):1124-33. [View Abstract]
  47. [Guideline] Patel TS, Greer SC, Skinner RB Jr. Cancer concerns with topical immunomodulators in atopic dermatitis: overview of data and recommendations to clinicians. Am J Clin Dermatol. 2007. 8(4):189-94. [View Abstract]
  48. Ring J, Mohrenschlager M, Henkel V. The US FDA 'black box' warning for topical calcineurin inhibitors: an ongoing controversy. Drug Saf. 2008. 31(3):185-98. [View Abstract]
  49. Simon D, Hosli S, Kostylina G, Yawalkar N, Simon HU. Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol. 2008 Jan. 121(1):122-8. [View Abstract]
  50. Bukutu C, Deol J, Shamseer L, Vohra S. Complementary, holistic, and integrative medicine: atopic dermatitis. Pediatr Rev. 2007 Dec. 28(12):e87-94. [View Abstract]
  51. Deo M, Yung A, Hill S, Rademaker M. Methotrexate for treatment of atopic dermatitis in children and adolescents. Int J Dermatol. 2014 Aug. 53(8):1037-41. [View Abstract]

Typical atopic dermatitis on the face of an infant.

Flexural involvement in childhood atopic dermatitis.

Typical atopic dermatitis on the face of an infant.

Flexural involvement in childhood atopic dermatitis.