D. Curt Chaffin
Definition: Atopic Dermatitis (AD) is a chronic inflammatory disorder of the skin which typically begins in early childhood and improves with age, but may continue into adulthood. The appearance of the lesions varies with time but they are always intensely pruritic. In the acute phase, the lesions appear erythematous and may have papules or vesicles before exhibiting scaling. In the chronic phase the lesions appear as raised, dry, crusting areas with thickened plaques of skin. The distribution varies by age with infants manifesting lesions on their cheeks and extensor surfaces of their extremities and neck. By school-age, this distribution has often shifted to the flexural areas of the antecubital and popliteal areas and may involve the ears. Adults may manifest the above symptoms or they may have only eczematous lesions found on their hands.
Pathogenesis: AD is likely the result of a Th2 biased immune response to various environmental stimuli. This results in increased levels of various inflammatory markers in proximity to the skin barrier as well as in the serum with the resulting clinical manifestation of inflamed skin. Some of this dysregulation of the immune response is indicated by increased serum IgE and eosinophils, increased IL-4 and IL-5 producing Th2 cells and increased IL-13 and IL-5.  These patients also exhibit increased numbers of macrophages and Th1 cells in the skin. Allergen specific T-cells are increased in number in the peripheral blood of patients with AD. Dendritic Langerhan's cells and macrophages in the atopic skin lesions express IgE on their cell surface.  Allergen exposure with subsequent immune response cause the increased release of various proinflammatory mediators from these cells.
Although there is still much to be discovered in the pathogenesis of AD, allergens clearly play a role in many patients with AD. In children, 30-50% have well-documented flares after exposure to certain foods, most commonly peanuts, eggs, soy, milk and wheat.  Aeroallergens may also play a role in the development of eczematous skin lesions. Some patients find that seasonal exacerbations of AD may closely correlate with levels of inhalant allergens  and experimental dust mite exposure has been found to worsen symptoms. Avoidance has been shown to improve symptoms. 
Microbes are another potential exacerbating factor. S aureus , herpes simplex and dermatophyte infections are among the infections which may exacerbate AD. Indeed, 90% of AD lesions are colonized by S aureus which produces exotoxins. These exotoxins can cause pruritis in AD patients and can function as superantigens. It is believed that the high rate of skin colonization in AD patients is due to the skin barrier defects in AD lesions. However, patients with psoriasis which also compromises the skin barrier have a much lower rate of skin infections.  This points to the fact that there are other mechanisms responsible of the increased rate of skin infections in addition to the breakdown of the skin barrier.
Certain microbes may exhibit a protective effect. A recent study has shown that pregnant women and subsequently their children given Lactobacillus had a significant decrease in the incidence of AD.  Ongoing studies here at the University of Michigan are exploring this further.
Cutaneous sensitization has been proposed as a mechanism whereby topical application of allergen not only increases allergen-specific skin sensitivity but also antigen-specific airway sensitivity. This has been shown to be the case in mice  but remains to be proven as a clinically relevant human route of sensitization.
A personal or family history of atopy predisposes one to develop AD and has been proposed as a major criteria for the diagnosis.(see table 1)  AD will affect 8-25% of populations worldwide and seems to be increasing in prevalence along with other atopic diseases. 
Diagnosis: There are no lab tests that make the diagnosis. Rather it is the characteristic history and physical findings which elucidate the diagnosis ( see table 1 ). These findings include pruritis at typical sites, early age of onset, chronic relapsing course and family or personal history of atopy.  Many of these patients will have elevated levels of IgE and peripheral eosinophil counts.  Patients with AD tend to have xerotic skin which may in part be a manifestation of the loss of cutaneous barrier function. As mentioned earlier, this loss of barrier function appears to be important as an entry point for allergens and microbes. Chronic lesions will often exhibit lichenification and older children may exhibit periorbital (Morgan's) folds and keratosis pilaris. Physical exam findings consistent with other allergic diseases may be present, including wheezing, pale nasal mucosa, allergic shiners or nasal creases.
Differential Diagnosis: Potentially serious diseases must be ruled out as some of these diseases have similar features to AD. These include cutaneous T-cell lymphoma, immunodeficiency syndromes, nutritional deficiencies, hyper IgE syndrome, Wiskott-Aldrich syndrome and pemphigus foliaceus. Other more common diseases include contact dermatitis, psoriasis, seborrhea, scabies and drug reactions.
Treatment Options:  Treatment relies on treating acute flares of the disease as well as prevention of future flares. Acute treatment includes topical steroids with oral steroids being reserved for refractory patients.  Treatment of acute flares of AD should be treated with higher potency topical steroids to quickly control symptoms rather than relying on lower potency steroids which are not likely to be effective. Potent topical corticosteroids can be used for several days avoiding thin areas of skin such as the face and skin fold areas. As is often the case, the lowest potency topical steroid which will control symptoms is the drug of choice. Side effects of topical steroids include hypopigmentation of the skin, thinning of the skin, development of striae and possible hypothalamic pituitary axis dysfunction. Care must be taken with infants, as their increased body surface area ratio puts them at risk for systemic side effects from topical steroids.
Newer calcineurin inhibitors that block T-cell function have been introduced and have greatly decreased the need for topical steroids. This class of drugs has a lower side effect profile than the topical steroids and thus can be used on the face and on a long term basis without the fear of skin thinning and hypopigmentation that accompanies topical steroids.   Examples currently available include tacrolimus (Protopic) and pimecrolimus (Elidel).
Prevention begins at identification of the first flare and continues long term. The general idea is to prevent irritation and further disruption of the skin. Preventing mechanical disruption of the skin is a major challenge in children and focuses on prevention of pruritis. Control of pruritis is key in the treatment of the patients as this is often the main irritating factor that patients complain of as well as being a factor that can exacerbate and complicate the disease process. Antihistamines are the primary drugs that have been used for control of pruritis and may involve both the sedating and non sedating classes. 
Restoration of the barrier function of the skin is paramount to improving the long term prognosis of this disease. Emollients are the mainstay in this regard and should be applied 2-3 times per day. They should be free of fragrances and perfumes. Skin creams should also be devoid of ingredients that may be allergic sensitizers. This includes substances such as proteins or oils from allergic sources such as tree nuts. Emollients may restore and protect the stratum corneum and thus preserve the skin barrier. 
Bathing is a controversial issue with recommendations varying from short showers to long hydrating baths. Many experts recommend 10-20 minute baths in lukewarm water with minimal gentle soap exposure and immediate application of emollients following soft toweling off of excess water. It is thought that emollients help slow the evaporation of water from the skin.
Identification and elimination of environmental factors that exacerbate AD are important for long term control. This involves avoidance of allergens and irritants. Care in choosing skin products such as soaps, shampoos, cleansers, lotions and moisturizers should be exercised with the least irritating and drying formulations chosen. Also rough clothing like wool should be avoided with cotton the material of choice. Environmental living conditions which promote perspiration should be avoided. Humidity is generally believed to be helpful for hydration of the skin; therefore, a humidifier in the home during the dry winter months may be helpful. In the summer, air conditioning may be useful in keeping the patient from becoming warm. Stress reduction has also been found useful in many patients.  It is unclear whether stress plays a more direct role in the exacerbation of lesions, or whether stress induces increase scratching which then in turn increases the flares of AD.
A combination of skin testing and patch testing may be used to predict which allergens may play a role. Negative skin testing is helpful for ruling out various potential allergens. Positive skin testing does not necessarily indict a particular allergen as a trigger in the disease process. As with other uses of skin testing, clinical correlation is important.  Once specific allergens have been identified, patients and their families can be instructed in avoidance measures.
These patients have increased susceptibility to skin infections especially by S aureus because of the poor barrier function of the skin. The infections in turn make the lesions worse and leave the patient at increased vulnerability to infections. This is a vicious cycle which must be interrupted if therapy is to be successful. Vigilance must be taken to identify and quickly treat impetigo to prevent further exacerbations in these patients.
Patients with atopic dermatitis also have increased susceptibility to viral skin infections from agents in the herpes virus family. Eczema herpeticum, widespread herpetic skin infection must be ruled out with any flare of eczema, and any involvement of facial dermatomes requires opthamologic evaluation to minimize spread to the eyes.
Immunotherapy has not been consistently useful for the management of AD and in general is not recommended. Topical antihistamines are not recommended due to the potential sensitization that may occur.
Prognosis/Natural History: AD is a chronic relapsing disease that has no known cure. Anticipatory guidance with parents regarding this point is important. However, clinical symptoms usually improve or disappear with age with up to 80% having no or little clinically noticeable disease by early adulthood.
Complications: There are several known complications of AD that should be monitored and quickly treated if discovered. These include optical diseases such as keratoconus, keratoconjunctivitis and anterior subcapsular cataracts which may develop during adolescence or early adult life. Skin infections as mentioned above should be treated aggressively and may rarely require IV therapy as in the case of eczema herpeticum.
Lichenification : Thickening of the skin with hyperkeratosis caused by chronic inflammation resulting from prolonged scratching or irritation.
Atopy : A hereditary disorder marked by the tendency to develop immediate allergic reactions to substances such as pollen, food, dander, and insect venoms and manifested by hay fever, asthma, or similar allergic conditions. Also called atopic allergy
Morgan's folds : Infraorbital folds in response to intense rubbing due to periorbital pruritis
Prurigo nodules - Pale, dome-shaped papules that itch severely with marked hypertrophy of the epidermis as a result of intense rubbing
Eczema - An acute or chronic noncontagious inflammation of the skin, characterized chiefly by redness, itching, and the outbreak of lesions that may discharge serous matter and become encrusted and scaly; typically refers to atopic dermatitis (atopic eczema)
Atopic dermatitis - Dermatitis characterized by intense itching, occurring in individuals predisposed to developing certain hypersensitivity reactions
Xerosis - Abnormal dryness, especially of the skin, eyes, or mucous membranes
Keratosis pilaris - a condition marked by the formation of hard conical elevations in the openings of the sebaceous glands especially of the thighs and arms that resemble permanent goose bumps
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