Atopic dermatitis (AD) (Figure 1), or hereditary eczema are interchangeable terms for an inflammatory condition of the skin characterized by erythema, pruritus, scaling, lichenification, and papulovesicles. AD is a distinct condition in individuals who are genetically predisposed to developing IgE-mediated hypersensitivity reactions. It is characterized by the "itch-scratch" cycle: affected individuals have the sensation of itch, followed by scratching and the subsequent creation of a rash. The classic triad of atopy includes eczema, asthma, and allergies. A wide range of environmental factors, such as contact allergens, stress, food, skin flora, and humidity, play a role in the development and severity of AD.

Perioral and periorbital dermatitis with hyperlinearity on the lower eyelid (Dennie-Morgan lines).

Figure 1

AD is a common condition affecting approximately 17% of the population,¹ with a slight female preponderance (1.3:1 in children). The incidence has increased 2-3 fold over the last 30 years. The basis of this increase in not well understood; however, environmental factors appear to play an important role in disease prevalence. Some factors associated with an increased risk of AD include small family size, higher socioeconomic and educational level irregardless of race, movement from rural to urban environment and increased use of antibiotics (the so-called "Western" lifestyle). This has led to the "hygiene hypothesis" which postulates that infections in early childhood (from less hygienic practices and older siblings) might prevent AD. This hypothesis is supported by evidence that infections induce type-1 helper T cells (T_H1), while there is a predominance of type-2 helper T cells (T_H2) in AD. T_H1 responses antagonize the development of T_H2 cells, thereby potentially decreasing the incidence of AD.²

Atopic dermatitis is a type I IgE-mediated hypersensitivity reaction, but the exact etiology is unknown. The pathogenesis is multifactorial and involves a complex immunologic cascade, including disruption of the epidermal barrier, IgE dysregulation, defects in the cutaneous cell-mediated immune response, and genetic factors.

The major elements in the immune dysregulation are Langerhans' cells, inflammatory dendritic epidermal cells, monocytes, macrophages, lymphocytes, mast cells, and keratinocytes, all of which interact through an intricate cascade of cytokines leading to a predominance of type-2 helper T cells (T_H2) over type-1 helper T cells (T_H1).³ The T_H2 cytokines, interleukin (IL)-4, IL-5, IL-10, and IL-13, are increased in the skin, and there is a corresponding decrease in T_H1 cytokines, mainly interferon gamma and IL-2.

Patients with AD often have dry, sensitive skin due to changes in the epidermis, which serves as a barrier to the environment by maintaining the water balance of the skin. Essential fatty acids (EFAs), such as linoleic and linolenic acid, are important components of the epidermal barrier. In AD, delta-6 desaturase activity is deficient, which leads to decreased linoleic and linolenic acid metabolites. Loss of EFAs results in increased transepidermal water loss and subsequent xerosis (dryness). The EFAs form the substrate of the inflammatory mediators – prostaglandins and leukotrienes, resulting in a secondary deficiency of prostaglandin E₁.

Defects in the epidermal barrier also lead to increased susceptibility to atopens (atopic allergens such as house dust mites, grass, or pollen). When such allergens contact atopic skin, they stimulate T_H2 lymphocytes to produce cytokines such as IL-4, IL-5, and IL-13, which in turn promote an increase in IgE synthesis.⁴ AD patients frequently have high levels of IgE antibodies to house dust mites and other allergens. Elimination of these allergens from the environment, an extremely difficult undertaking, can lead to improvement of AD.

Defective cell-mediated immunity leads to increased susceptibility to many bacterial, viral, and fungal infections of the skin. Children with AD are particularly susceptible to severe, widespread herpes simplex virus infection (eczema herpeticum), a systemic and potentially fatal infection affecting primarily areas of active eczema. Widespread infections with human papillomavirus (warts) and molluscum contagiosum are also common in children with AD.

Many factors exacerbate or trigger AD, including colonization with Staphylococcus aureus, stress, anxiety, systemic illness, and xerosis. The most common trigger is S aureus colonization. More than 90% of patients with AD have S aureus colonization of lesional skin, and more than 75% have colonization of uninvolved skin.⁵ Staphylococci exacerbate AD by two mechanisms: acting as superantigens by stimulating an augmented T-cell response, thereby leading to exacerbation of skin disease, and promoting increased production of IgE. IgE has anti-S aureus properties and helps to control colonization and infection in normal individuals. In AD patients, the elevated IgE levels contribute to immune dysregulation. Treatment with topical and/or oral anti-staphylococcal antibiotics decreases the colonization of the skin and often leads to improvement of the dermatitis.

Family studies support a genetic basis for AD. When both parents are atopic, their offspring have a 70% risk for AD,⁶ with a higher risk of inheritance if the mother is atopic. The mode of inheritance appears to be complex and likely involves multiple genes. To date, no specific single gene has been identified as a unique marker for AD or atopy.⁷

AD is a chronic disease with periods of remission and exacerbations. Three age-related stages exist: the infantile stage (up to 2 years old), the childhood stage (from 2 to 12 years), and the adult stage (puberty onward). The manifestations vary with age, even within the same patient. All stages are characterized by xerosis, fissures, pruritus, and lichenification. The main differentiating factor is the area of involvement.

The infantile stage is characterized by very pruritic, red, eczematous plaques on the cheeks and extensor extremities. Secondary impetiginization, with honey-colored crust, is common in infants. Scalp involvement may resemble seborrheic dermatitis. The diaper area is spared.

The childhood stage is primarily a papular dermatitis affecting the flexural areas, especially the antecubital and popliteal fossae, wrists, ankles, and neck. Thickened, lichenified plaques with excoriation (Figures 2, 3, 4) are common. In darker pigmented children, follicular papules may be the only manifestation. Hypopigmentation and hyperpigmentation may occur, which can cause great anxiety in parents. Pityriasis alba, characterized by hypopigmented, scaly patches on the face, is commonly seen. Keratosis pilaris, or spiny hair follicles, commonly affect the posterior aspect of the upper arms, and the anterior thighs.

The adult stage is unpredictable. Affected patients may have had only a few outbreaks since infancy, or they may have had a chronic, relapsing course. The hand dermatitis is common and may be the only manifestation of adult AD, which may lead to significant disability. Like affected children, adults also frequently have lichenification of the flexures and facial dermatitis.

The diagnosis of AD depends on a personal and/or family history of atopy coupled with the clinical signs and symptoms described by Hanifin⁸ (Table 1). Pruritus and xerosis are key elements. Without them, the diagnosis should be questioned.⁵

Atopic dermatitis may resemble other types of dermatitis (seborrheic dermatitis, allergic contact dermatitis, irritant contact dermatitis) and dermatophytosis. It may be a component of rare genetic diseases such as Netherton's syndrome, ichthyoses, and immunodeficiency syndromes (eg, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, isolated IgA deficiency, and severe combined immunodeficiency disease). Helpful diagnostic tests include a serum IgE level, serum protein electrophoresis, fungal scraping for potassium hydroxide preparation and culture, and skin biopsy.

Atopic dermatitis tends to be a chronic relapsing disease. The goals of therapy should be to reduce the number and severity of flares and to increase the number of disease-free periods. The mainstay of treatment for AD is hydrating the skin with the regular use of emollients and suppressing cutaneous inflammation with topical corticosteroids. Topical calcineurin inhibitors have recently become an important adjunctive therapy. For severe disease, especially during acute flares, systemic corticosteroids may be necessary. Secondary infections require treatment with topical and/or oral antibiotics. Oral antihistamines may help decrease pruritus. In severe, recalcitrant cases, phototherapy or systemic immunosuppressive medications may be necessary.

Most patients with AD require hydration though the liberal use of bland emollients, which serve to hydrate the stratum corneum and maintain the lipid barrier. Sufficient emollients applied liberally several times a day may be enough to significantly reduce the disease activity of AD. Parents of infants and toddlers should apply a bland emollient to the entire body with each diaper change. Older children should apply bland emollients in the morning, after school, and at bedtime. Bathing should be limited to brief, cool showers once daily. Soap, which dries and irritates the skin, should be avoided, but gentle lipid-free cleansers are beneficial.

Corticosteroids suppress lymphocyte activity in the skin, thereby decreasing inflammation. Affected patients can use a low-potency topical steroid (hydrocortisone or desonide) for day-to-day control of mild disease, and a medium-potency steroid (triamcinolone acetonide, fluticasone or fluocinolone) for more severe flares. Low-potency topical steroids are suitable for infants and for intertriginous and sensitive areas (eg, the face or genitals). More potent steroids should be avoided on these sites. Severe, widespread disease may require systemic corticosteroids. Because of the well-known side effects of systemic corticosteroids (eg, adrenal suppression, osteoporosis, hypertension, diabetes, obesity, striae, and so on), their use should be limited to the most severe disease.

Topical calcineurin inhibitors (TCI’s) (tacrolimus, pimecrolimus) are effective alternatives to the chronic use of topical corticosteroids. TCI’s bind calcineurin and block the activation of T-cells by cytokines, thus halting the inflammatory cascade that leads to AD. TCI’s are especially suitable for more delicate areas such as the face and genitals as they do not carry the risk of atrophy, telangectasias, and striae associated with the chronic use of steroids. Recent reports have surfaced suggesting a possible risk of lymphoma associated with the use of high-dose oral pimecrolimus in animal studies (A), prompting the FDA to put out a “black box” warning advising against the use of TCI’s in children younger than 2 years. However, there is no data to support an increased risk of lymphoma with topical treatment in humans (A). TCI’s should be used for a limited period of time and only on affected skin. They should not be used as a daily moisturizer, first-line therapy or as a preventative therapy.

The pruritus associated with atopic dermatitis can be severe and often interferes with school, work, and sleep. Despite a lack of objective data to support their use, antihistamines are commonly used to break the itch-scratch-itch cycle.⁹ Nonsedating antihistamines such as fexofenadine, cetirizine, loratidine, and desloratidine can help offset daytime itching without somnolence. Sedating antihistamines such as diphenhydramine or hydroxyzine are often helpful for nighttime pruritus.

Patients with atopy have an abnormal tolerance to S aureus colonization of the skin, which can exacerbate the dermatitis. Affected patients should use lipid-free antibacterial cleansers. For open wounds, a topical antibiotic such as mupirocin can help to prevent secondary impetiginization (Figures 5,6). An oral antibiotic with S aureus coverage and good skin penetration, such as ampicillin/clavulanic acid, cephalexin, or azithromycin, is necessary for extensive excoriations and impetigo.

In severe, recalcitrant cases, ultraviolet light treatments (UVB or PUVA) and immunosuppressive medications (eg, methotrexate, cyclosporine, azathioprine, mycophenolate mofetil) may be helpful.⁹ These should be used very cautiously and with close monitoring, and should be reserved for the most severe cases.

Allergic contact dermatitis to topical medications, cosmetics, or metals should be considered in patients with recalcitrant disease. Evaluation by an environmental dermatologist and an allergist, including patch, pinprick, and serum radioallergosorbent testing (RAST), may be warranted. Topical medications that are known sensitizers, such as lidocaine, doxepin cream, and diphenhydramine cream, as well as topical antibiotics such as neomycin, should be strictly avoided. Allergic contact dermatitis to topical steroids should be considered in any patient who fails to improve or worsens with the use of topical steroids.

Atopic dermatitis is a chronic disease with intermittent flares and spontaneous remissions. Approximately 40% to 60% of children with AD have the disease in adulthood, usually manifested as hand dermatitis. More than 75% of children with AD also have asthma or allergic rhinitis.

With good skin care, moisturization, and the use of topical corticosteroids and/or topical calcineurin inhibitors, most patients with atopic dermatitis do well.

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