eMedicine Specialties > Pediatrics: General Medicine > Dermatology

Atopic Dermatitis

Caroline C Spagnola, MD, Consulting Staff, Department of Allergy and Immunology, Kaiser Permanente Bellflower

Updated: Sep 30, 2009

Introduction

Background

Atopic dermatitis (AD) is a chronically relapsing skin disorder with an immunologic basis. 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, 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.

Typical atopic dermatitis on the face of an infant.

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.¹

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.^1,2

Frequency

United States

Atopic dermatitis occurs in approximately 10-20% of children and 2% of adults.¹ 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.³ 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.⁴ 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%.⁵

Clinical

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.⁶ Appropriate cases must have at least 3 major characteristics and at least 3 minor characteristics.

• Major characteristics include the following:
  • Pruritus
  • Typical morphology and distribution (ie, flexural lichenification and linearity in adults, facial and extensor involvement in infants and young children)
  • Chronic or chronically relapsing dermatitis
  • Personal or family history of atopy (eg, asthma, allergic rhinoconjunctivitis, atopic dermatitis)
• Minor characteristics are as follows:
  • Xerosis (dry skin)
  • Ichthyosis, palmar hyperlinearity, keratosis pilaris
  • Hand dermatitis, foot dermatitis
  • Cheilitis
  • Nipple eczema
  • Susceptibility to cutaneous infection (eg, with Staphylococcus aureus, herpes simplex virus [HSV], other viruses, warts, molluscum, dermatophytes)
  • Erythroderma
  • Perifollicular accentuation
  • Pityriasis alba
  • Early age of onset
  • Impaired cell-mediated immunity
  • Recurrent conjunctivitis
  • Orbital darkening
  • Infraorbital fold (eg, Dennie pleat, Morgan fold)
  • Anterior neck folds
  • Keratoconus
  • Anterior subcapsular cataracts
  • Sensitivity to emotional factors
  • Food intolerance
  • Pruritus with sweating
  • Intolerance of wool
  • White dermographism
  • Immediate type I skin test response
  • Elevated total serum immunoglobulin E (IgE)
  • Peripheral blood eosinophilia

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. This is clinically observed as a history of repeated unusual cutaneous infections (eg, eczema herpeticum, warts, molluscum, dermatophytes).

Physical

• Three classes of skin lesions are recognized.
  • Acute - Intensely pruritic erythematous papules and vesicles overlying erythematous skin; frequently associated with extensive excoriations and erosions accompanied by serous exudates
  • Subacute - Erythema, excoriation, and scaling
  • Chronic - Thickened plaques of skin, accentuated skin markings (lichenification), fibrotic papules (prurigo nodularis); possible coexistence of all 3 types of lesions in chronic atopic dermatitis
• Typical locations of lesions by age
  • Nonmobile infant - Face and scalp
  • Crawling infant - Extensor surfaces of extremities, trunk, face, and neck
  • Older child and adolescent - Wrists, ankles, antecubital fossae, popliteal fossae, and neck
  • Adult - May be limited to hand and foot eczema
• 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.
  • 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.

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. Much higher concordance rates for atopic dermatitis are observed in monozygotic twins (77%) than in dizygotic twins (15%).¹
• 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.⁷
• 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 interleukin (IL)-31 expression in skin. IL-31 has been shown to induce pruritus and skin lesions resembling atopic dermatitis in mice.¹
    • 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.¹
  • Food allergy is implicated 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.¹ The most common food allergens in children include 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.

Differential Diagnoses

Other Problems to Be Considered

Seborrheic dermatitis
Psoriasis

Workup

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 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 the 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).

Treatment

Medical Care

• 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.⁴ 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.
• 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.⁸
  • 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.⁸ 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 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. 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 infectedsores.²
  • 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. Hot water induces vasodilatation with increased weeping and pruritus; 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 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. However, UVA 1 light sources continue to be prohibitively expensive and are not yet standardized equipment in nonacademic treatment centers nor readily available enough to recommend. A small number of patients develop erythema or disease flares with light treatment.
• 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.⁹

Consultations

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

• Atopic dermatitis that is severe (eg, 20% skin involvement, 10% skin involvement with eyelids/hands/intertriginous areas affected) or is refractory to first-line treatments
• Erythroderma or extensive exfoliation
• Infectious complications
• Ocular complications
• Psychosocial complications
• Coexisting asthma or allergic rhinitis
• Impaired quality of life
• Identification of triggers and allergens
• Atopic dermatitis requiring hospitalization or more than one course of systemic steroids
• Uncertain diagnosis

Diet

• A clinical report from the American Academy of Pediatrics recommended exclusive breastfeeding over cow's milk formula feeding in the first 4 months of life to prevent development of atopic dermatitis in infants at high risk of developing atopy.¹⁰ Furthermore, supplementation with extensively hydrolyzed formulas in this same group of high-risk infants appeared to be more effective at preventing development of atopic dermatitis than supplementation with partially hydrolyzed formulas or cow's milk formulas.
• Many physicians are currently advocating elimination of specific commonly allergenic foods during the first 1-2 years of life in children with acute atopic dermatitis. The short list includes cow's milk, eggs, tomatoes, citrus fruits, chocolate, wheat products, spiced foods, fish, nuts, and peanut butter. These foods may be reintroduced after controlling the initial acute flare of atopic dermatitis, or parents may elect to wait until after the child is aged 2 years because food reactivity diminishes markedly with age.
• 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 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.

Medication

Topical corticosteroids are the mainstay of treatment of atopic dermatitis (AD). 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.

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 work the best on 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. 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.

Systemic cyclosporin A can dramatically reverse severe flares of atopic dermatitis. Because of the risk of severe adverse effects, this treatment should be limited in duration. Once control is obtained, alternative maintenance therapy should be instituted.

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).¹¹

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. However, larger trials to evaluate safety and long-term efficacy are needed.¹²

Conflicting results have been reported regarding the use of probiotics (eg, Lactobacillus, Bifidobacterium) in preventing atopic dermatitis or in controlling symptoms in children.¹² 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.¹³ Further studies on the subject are needed prior to developing firm conclusions on the usefulness of this complementary medicinal treatment.

Topical corticosteroids

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. Remember to use only lower potency steroids on the face, axillae, groin, and intertriginous areas because of increased absorption.

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 as 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.

Hydrocortisone (Cortizone, Dermolate, Westcort)

Adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. It has mineralocorticoid and glucocorticoid effects resulting in anti-inflammatory activity.

Dosing

Adult

1% or 2.5%: Apply sparingly bid to areas of mild eczema, preferably after baths
2.5% or 5%: Apply sparingly bid to areas of moderate eczema
2.5%: Apply sparingly bid to face and intertriginous areas affected by severe eczema

Pediatric

Infants: Apply 0.5% sparingly to affected skin bid in mild-to-moderate eczema; 1% bid in moderate-to-severe eczema
Older children: Apply 1% sparingly to affected skin bid for mild-to-moderate eczema; 2.5% bid in severe eczema
Adolescents: Apply 2.5% or 5% sparingly to affected skin bid for moderate eczema

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use, applying over large surface areas, application of potent steroids, and occlusive dressings may increase systemic absorption of corticosteroids and cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria

Triamcinolone (Kenalog)

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

Dosing

Adult

0.025%: Apply sparingly to trunk and extremities bid/tid for mild to moderate AD
0.1%: Apply sparingly to trunk and extremities bid/tid for moderate AD
0.5%: Apply sparingly to trunk and extremities bid/tid for severe AD

Pediatric

Infants and young children: Apply 0.025%-0.1% sparingly to trunk and extremities bid/tid for severe AD
Adolescents: Apply 0.025%-0.1% sparingly to trunk and extremities bid/tid for moderate AD.
Apply 0.5% sparingly to trunk and extremities bid/tid for severe AD

Interactions

None reported

Contraindications

Documented hypersensitivity; fungal, viral, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use in decreased skin circulation; prolonged use, applications over large areas, and use of potent steroids and occlusive dressings may result in systemic absorption; systemic absorption may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria

Flurandrenolide (Cordran Tape)

Intermediate-potency topical corticosteroid. Each square cm provides 4 mcg.

Dosing

Adult

Apply to trunk or extremities for 8-12 h qd on successive days for chronic, lichenified patches of AD

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; application with plastic wrap in acutely infected areas or in areas with enhanced absorption of topical steroids (eg, face, axillae, groin, intertriginous areas) because of the increased risk of adverse effects

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use extreme caution to prevent overuse and consequent development of skin changes, including atrophy, striae, or local infection (eg, miliaria, folliculitis)

Systemic corticosteroids

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.

Prednisone (Deltasone, Orasone)

Decreases inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

1-2 mg/kg/d PO for 7- to 14-d pulse therapy; followed by slow taper

Pediatric

Adolescents with severe refractory eczema: Administer as in adults

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Development of striae, atrophy of skin, perioral dermatitis, rosacea, and telangiectasias; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Antimicrobials

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.

Mupirocin topical cream or ointment (Bactroban)

Inhibits bacterial growth by inhibiting RNA and protein synthesis.

Dosing

Adult

Apply a thin film topically to the affected area 2-5 times per d for 5-14 d

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Prolonged use may result in the growth of nonsusceptible organisms

Cephalexin (Keflex, Keftab)

First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora.

Dosing

Adult

250-500 mg PO qid

Pediatric

25-100 mg/kg/d PO divided qid

Interactions

Coadministration with aminoglycosides increases nephrotoxic potential

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment

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

Macrolide antibiotics that inhibit bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.

Dosing

Adult

Erythromycin: 250-500 mg PO qid
Azithromycin: 500 mg PO on day 1, followed by 250 mg PO qd for next 4 d

Pediatric

Erythromycin: 30-50 mg/kg/d PO divided tid/qid
Azithromycin: 10 mg/kg PO on day 1, followed by 5 mg/kg PO qd for next 4 d

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in liver disease

Oxacillin or dicloxacillin

Bactericidal antibiotic that inhibits cell wall synthesis. Used in the treatment of infections caused by penicillinase-producing staphylococci. May be used to initiate therapy when a staphylococcal infection is suspected.

Dosing

Adult

Oxacillin: 500-1000 mg PO q4-6h
Dicloxacillin: 125-500 mg PO qid

Pediatric

Oxacillin: 50-100 mg/kg/d PO divided q6h
Dicloxacillin: 25-100 mg/kg/d PO divided q6h

Interactions

Decreases efficacy of PO contraceptives; increases effects of anticoagulants; probenecid and disulfiram may increase levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Amoxicillin and clavulanate (Augmentin)

Drug combination treats bacteria resistant to beta-lactam antibiotics. Base dosage regimen on amoxicillin content. Because of different amoxicillin-clavulanic acid ratios in 250-mg tab (250/125) versus 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.

Dosing

Adult

250-500 mg PO tid or 500-875 mg PO bid

Pediatric

20-40 mg/kg/d PO divided tid or 25-45 mg/kg/d PO divided bid

Interactions

Increased risk of amoxicillin rash with concurrent allopurinol; probenecid and disulfiram may increase penicillin levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Acyclovir (Zovirax)

Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h of rash onset. May prevent recurrent outbreaks.

Dosing

Adult

Herpes zoster: 800 mg PO 5 times per d for 7-10 d
Varicella-zoster: 800 mg PO qid for 5 d

Pediatric

Mucocutaneous HSV: 25-30 mg/kg/d PO divided q8h for 7-10 d for initial infection or for 5 d for recurrence
Varicella zoster: 80 mg/kg/d PO divided qid for 5 d; not to exceed 3200 mg/d

Interactions

Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or when using nephrotoxic drugs

Ketoconazole (Nizoral)

Imidazole broad-spectrum antifungal agent. Inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

Dosing

Adult

Tinea: Apply 2% cream to affected skin bid
Scalp involvement: Use 2% shampoo twice a week

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

If sensitivity or irritation develops, discontinue use; for external use only; avoid contact with eyes

Antipruritics

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

Pramoxine (Prax, PrameGel) or doxepin topical cream (Zonalon)

Pramoxine elicits anesthetic effect by blocking nerve conduction and impulses by inhibiting depolarization of neurons. Doxepin topical cream is a potent antihistamine and is indicated for pruritus.

Dosing

Adult

Pramoxine: Apply to affected skin tid/qid prn for pruritus
Doxepin: Apply 5% cream to affected skin qid

Pediatric

Pramoxine: Apply to affected skin tid/qid prn for pruritus
Doxepin: Not recommended

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Pramoxine: Caution in patients with trauma in area to be treated
Doxepin: >20% of patients experience drowsiness if applied to >10% of body surface area

Diphenhydramine (Benadryl), hydroxyzine (Vistaril), or doxepin (Sinequan)

For symptomatic relief of symptoms caused by release of histamine in allergic reactions.

Dosing

Adult

Diphenhydramine: 25-50 mg PO qhs or q6h
Hydroxyzine: 25-50 mg PO qhs or q4-6h
Doxepin: 25-75 mg PO qhs

Pediatric

Diphenhydramine: 5 mg/kg/d PO divided q6h
Hydroxyzine: 2 mg/kg/d PO divided q6-8h
Doxepin: Not recommended

Interactions

CNS depression may increase with alcohol or other CNS depressants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and thyroid replacement therapy

Immunomodulators

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. 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. 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.

Physicians are advised to use the following guidelines when prescribing topical immunomodulators such as tacrolimus and pimecrolimus:^14,15

• Use in patients older than 2 years.
• Use intermittently as needed, not on a daily basis for prolonged periods (ie, >6 weeks).
• Avoid use in immunocompromised patients or in those with neoplasms.
• Atypical atopic dermatitis, including new onset disease in an adult, should warrant a skin biopsy prior to topical immunomodulator use, to rule out other diagnoses (eg, cutaneous T-cell lymphoma, Netherton syndrome).
• Encourage sun protection to reduce the risk of photocarcinogenesis.

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.

A small, nonrandomized, nonblinded study of 6 patients with severe atopic dermatitis showed significant improvement in skin symptoms within the first 4-8 weeks of treatment with Rituximab.¹¹ Larger, randomized controlled studies are needed to verify this finding.

Tacrolimus, topical (Protopic)

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-a, 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 downregulate the expression of FCeRI on Langerhans cells. 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 where 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%.

Dosing

Adult

Apply 0.03% or 0.1% to affected skin bid
For short-term and intermittent use only

Pediatric

<2 years: Not established
2-15 years: Apply 0.03% to affected skin bid
>15 years: Administer as in adults
For short-term and intermittent use only

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients may experience a burning sensation during first few days of application; skin can become photosensitive, caution patients about exposure to direct or artificial sunlight and encourage use of sunscreen; safety and efficacy in infected AD is not known; application under occlusion, which may promote systemic exposure, has not been evaluated (do not use tacrolimus ointment with occlusive dressings); absorption of tacrolimus following topical applications of tacrolimus ointment is minimal (relative to systemic administration), but tacrolimus is excreted in human milk and, thus, a decision should be made whether to discontinue breastfeeding or to discontinue drug, taking into account importance of drug to mother (potential for serious adverse reactions in breastfeeding infants from tacrolimus should also be a concern)
The FDA issued a public health advisory in 2004 based on reports of a possible link between use of the topical calcineurin inhibitors and malignancies; this concern is based on information from animal studies, case reports in a small number of patients, and knowledge of how drugs in this class work; human studies of 10 years or longer may be needed to determine if Protopic is linked to cancer; in the meantime, this risk is uncertain, and the FDA advises that Protopic should be used only as labeled and only after other prescription treatments have failed to work or cannot be tolerated

Pimecrolimus (Elidel cream)

First nonsteroid cream approved in the US for mild-to-moderate atopic dermatitis. Derived from ascomycin, a natural substance produced by 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. Available as a 1% cream.

Dosing

Adult

Apply topically to affected areas bid
Short-term and intermittent use only

Pediatric

<2 years: Not established
>2 years: Administer as in adults
Short-term and intermittent use only

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Potential exacerbation of existing infection at site of application; may cause burning and irritation; caution with conditions that suppress the immune system (eg, AIDS, cancer); possible risk of lymph node or skin cancer based on animal studies and a small number of patients; may increase risk of viral infections; other adverse effects include headache, sore throat, flulike symptoms, fever, and cough
The FDA issued a public health advisory in 2004 based on reports of a possible link between use of the topical calcineurin inhibitors and malignancies, this concern is based on information from animal studies, case reports in a small number of patients, and knowledge of how drugs in this class work; human studies of 10 years or longer may be necessary to determine if use of Elidel is linked to cancer; in the meantime, this risk is uncertain, and the FDA advises Elidel should be used only as labeled after other prescription treatments have failed to work or cannot be tolerated

Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions.

Dosing

Adult

5 mg/kg/d PO qd

Pediatric

Not established

Interactions

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Contraindications

Documented hypersensitivity; uncontrolled hypertension or malignancies; concomitant administration with PUVA or UVB radiation in psoriasis (may increase risk of cancer)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO

Follow-up

Further Outpatient Care

• 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.

Deterrence/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:¹⁶
  • Skin care products that contain alcohol and astringents should be avoided.
  • New clothes should be laundered before use to remove formaldehyde and other chemicals.
  • Liquid detergents are preferred over powder detergents for laundering clothes, as liquids are easier to rinse out. A second rinse cycle may also improve removal of residual detergent.
  • Patients should shower immediately after swimming in chlorinated pools and should subsequently apply moisturizer.
  • Fragrance-free skin products that are hypoallergenic or made for "sensitive skin" may be less irritating than other kinds of skin products.
• 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.¹³ Larger, randomized controlled studies are needed to confirm these initial findings.
• A dog living in the home at the time of birth has also been associated with a 50% decrease in the incidence of atopic dermatitis at age 3 years.¹⁷

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 (e.g. nafcillin, oxacillin, dicloxacillin) if S aureus is a possible cause. Hospitalization and use of intravenous antibiotics are indicated in cases of invasive infection (e.g. 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).

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 eMedicine's Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Eczema.

Multimedia

Media file 1: Typical atopic dermatitis on the face of an infant.

Media file 2: Flexural involvement in childhood atopic dermatitis.

References

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Keywords

atopic dermatitis, AD, eczema, immunologic skin disorder, hyperactive T helper cell 2, hyperactive Th2, elevated serum immunoglobulin E, elevated serum IgE, deficient levels of omega-6 fatty acids, disorder of fatty acid metabolism, pruritus, dermatitis, flexural lichenification and linearity in adults, facial and extensor involvement in infants and young children, atopy, dry skin, xerosis, skin inflammation, inflamed skin, asthma, hayfever, Staphylococcus aureus, herpes simplex virus, HSV, warts, molluscum, dermatophytes, food intolerance, keratosis pilaris, accentuated palmar creases, lichenification, atopic pleats, allergic shiners, transverse nasal crease

Contributor Information and Disclosures

Author

Caroline C Spagnola, MD, Consulting Staff, Department of Allergy and Immunology, Kaiser Permanente Bellflower
Caroline C Spagnola, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, and American College of Allergy, Asthma and Immunology
Disclosure: Nothing to disclose.

Medical Editor

Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center
Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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