Atopic dermatitis (AD) is a pruritic disease of unknown origin that usually starts in early infancy (an adult-onset variant is recognized); it is characterized by pruritus, eczematous lesions, xerosis (dry skin), and lichenification (thickening of the skin and an increase in skin markings). AD may be associated with other atopic (immunoglobulin E [IgE]) diseases (eg, asthma, allergic rhinitis, urticaria, acute allergic reactions to foods).1 AD has enormous morbidity, and the incidence and prevalence appear to be increasing. Other conditions with different etiologies and prognoses are often grouped under the umbrella of a diagnosis of AD.
Good evidence indicates that genetic factors are important in the development of atopic dermatitis (AD), but the pathophysiology is still poorly understood. Two main hypotheses have been proposed regarding the development of the inflammatory lesions. The first suggests an immune dysfunction resulting in IgE sensitization and a secondary epithelial-barrier disturbance. The second proposes a defect in epithelial cells leading to the defective barrier problem, with the immunological aspects being epiphenomena.
In healthy individuals, balance exists between 2 important subdivisions of T cells (ie, TH 1, TH 2). The immune hypothesis invokes an imbalance in the T lymphocytes, with TH 2 cells predominating; this results in cytokine production of interleukins 4, 5, 12, and 13 and granulocyte macrophage colony-stimulating factor, causing an increase in IgE and lowered interferon gamma levels. Later, in persons with chronic AD, the TH 1-type cells predominate. Other cell types are also involved in the process, including eosinophils, Langerhans cells, keratinocytes, and B cells.2
The second hypothesis involves defective barrier function in the stratum corneum of AD patients, leading to the entry of antigens that result in the production of inflammatory cytokines. Some authors question whether the antigens can also be absorbed from the gut (eg, from food) and the lungs (eg, from house dust mites). Xerosis is known to be an associated sign in many AD patients. Evidence has shown multiple loss-of-function mutations in the filaggrin gene (FLG) on band 1q21.3 in patients with AD in Europe and other filaggrin mutations in Japanese patients. This gene is mutated in persons with ichthyosis vulgaris; it is associated with early-onset AD and with airway disease in the setting of AD. These changes are only found in 30% of European patients, begging the question of whether other genetic variants may also be responsible for some of the findings in the pathogenesis of AD.
In AD, transepidermal water loss is increased. Defective lamellar bodies may be caused by abnormalities of ceramide production. Whether the inflammation causes primary or secondary epidermal barrier breakdown is not known, but with the knowledge that filaggrin is involved in epithelial disruption, it is now thought that this finding leads to increased transepidermal penetration of environmental allergens, increasing inflammation and sensitivity.3, 4
The prevalence rate is 10-12% in children and 0.9% in adults. More recent information examining physician visits for AD in the United States from 1997-2004 estimates a large increase in office visits for AD occurred. In addition, blacks and Asians visit more frequently for AD than whites. Note that this increase involves all disease under the umbrella of AD and it has not been possible to allocate which type has increased so rapidly.5
The prevalence rate is rising, and AD affects 15-30% of children and 2-10% of adults. This figure estimates the prevalence in developed countries. In China and Iran, the prevalence rate is approximately 2-3%. The frequency is increased in patients who immigrate to developed countries from underdeveloped countries.6
Incessant itch and work loss in adult life is a great financial burden. A number of studies have reported that the financial burden to families and government is similar to that of asthma, arthritis, and diabetes mellitus. In children, the disease causes enormous psychological burden to families and loss of school days. Mortality due to AD is unusual.
Kaposi varicelliform eruption (eczema herpeticum) is a well-recognized complication of AD.
It usually occurs with a primary herpes simplex infection, but it may also be seen with recurrent infection. Vesicular lesions usually begin in areas of eczema and spread rapidly to involve all eczematous areas and healthy skin. Lesions may become secondarily infected. Timely treatment with acyclovir ensures a relative lack of severe morbidity or mortality.
Another cause of Kaposi varicelliform eruption is vaccination with vaccinia for the prevention of small pox, but because this is no longer mandatory, patients with AD do not develop the sequelae of eczema vaccinatum that has been seen in the past. It was usually contracted by the patient from the vaccination of themselves or their close relatives. This condition had a high mortality rate (up to 25%). In the current climate of threats of bioterrorism, vaccination may once again become necessary, and physicians should be aware of eczema vaccinatum in this setting.
Note that chickenpox vaccine does not carry the same risk as herpes simplex and vaccinia.
Bacterial infection with Staphylococcus aureus or Streptococcus pyogenesis is not infrequent in the setting of AD . The skin of patients with AD is colonized by S aureus. Colonization does not imply clinical infection, and physicians should only treat patients with clinical infection. The emergence of methicillin-resistant S aureus (MRSA) may prove to be a problem in the future in these patients. Eczematous and bullous lesions on the palms and soles are often infected with beta-hemolytic group A Streptococcus.
Urticaria and acute anaphylactic reactions to food occur with increased frequency in patients with AD. The food groups most commonly implicated include peanuts, eggs, milk, soya, fish, and seafood. In studies in peanut-allergic children, the vast majority were atopic.
Latex allergy is more common in patients with AD than in the general population.
Of AD patients, 30% develop asthma and 35% have nasal allergies.
AD affects persons of all races. Immigrants from developing countries living in developed countries have a higher incidence of AD than the indigenous population, and the incidence is rapidly rising in developed countries
The male-to-female ratio is 1:1.4.
In 85% of cases, AD occurs in the first year of life; in 95% of cases, it occurs before age 5 years. The incidence of AD is highest in early infancy and childhood. The disease may have periods of complete remission, particularly in adolescence, and may then recur in early adult life.
In the adult population, the rate of AD frequency is 0.9%, but onset may be delayed until adulthood.
The Medscape Pediatric Dermatology Resource Center may be helpful.
Incessant pruritus is the only symptom of atopic dermatitis (AD); children often scratch themselves uncontrollably. Although pruritus may be present in the first few weeks of life, parents become more aware of the itch as the itch-scratch cycle matures when the patient is aged approximately 3 months. The disease typically has an intermittent course with flares and remissions occurring, often for unexplained reasons.
Primary findings of atopic dermatitis (AD) include xerosis, lichenification, and eczematous lesions. Excoriations and crusting are common. The eczematous changes and its morphology are seen in different locations depending on the age of the patient.
AD is usually noticed soon after birth. Xerosis occurs early and often involves the whole body; the diaper area is usually spared.
The earliest lesions affect the creases (antecubital and popliteal fossae), with erythema and exudation. Over the following few weeks, lesions usually localize to the cheeks, the forehead and scalp, and the extensors of the lower legs; however, they may occur in any location on the body, usually sparing the diaper area. Lesions are ill-defined, erythematous, scaly, and crusted (eczematous) patches and plaques.
Lichenification is seldom seen in infancy.
Xerosis is often generalized. The skin is flaky and rough.
Lichenification is characteristic of childhood AD. It signifies repeated rubbing of the skin and is seen mostly over the folds, bony protuberances, and forehead.
Lesions are eczematous and exudative. Pallor of the face is common; erythema and scaling occur around the eyes. Dennie-Morgan folds (ie, increased folds below the eye) are often seen. Flexural creases, particularly the antecubital and popliteal fossae, and buttock-thigh creases are often affected.
Excoriations and crusting are common. The crusting with AD should not be confused with infection because both may manifest oozing and crusting.
Lesions become more diffuse with an underlying background of erythema. The face is commonly involved and is dry and scaly.
Xerosis is prominent.
Lichenification may be present.
A brown macular ring around the neck is typical but not always present. It represents localized deposition of amyloid.
Until Hanifin and Rajka7 developed diagnostic criteria for the diagnosis of AD in 1980, no standardized methods were available to make the diagnosis. Since then, numerous other experts have developed different criteria suitable for their own environment, and varying with age. The original criteria of Hanifin and Rajka have been modified many times. Efforts to develop practical clinical criteria have not been successful, and those available are not suitable for all geographic areas and age groups. The lack of a good chemical marker for diagnosing the disease is an enormous obstacle to the study of AD.
The following is a constellation of criteria commonly used for the diagnosis of AD:
Eczematous changes that vary with age
Chronic and relapsing course
Early age of onset
Atopy (IgE reactivity)
Personal history of asthma or hay fever or a history of atopic diseases in a first-degree relative in patients younger than 4 years
Onset younger than age 2 years (not used if child is aged <4 y)
A firm diagnosis of AD depends on excluding conditions such as scabies, allergic contact dermatitis, seborrheic dermatitis (SD), cutaneous lymphoma, ichthyosis, psoriasis, immunodeficiency, and other primary disease entities.
Genetics8, 9: A family history of AD is common. Genome-wide scans have highlighted several atopic dermatitis (AD) related loci on 3q21, 1q21, 16q, 17q25, 20p, and 3p26. Several candidate genes have been identified (5q31-33); they all encode cytokines involved in the regulation of IgE synthesis.
Infection: The skin of patients with AD is colonized by S aureus. Clinical infection with S aureus often causes a flare of AD, and S aureus has been proposed as a cause of AD by acting as a superantigen.
Hygiene: The hygiene hypothesis is touted as a cause for the increase in AD. This attributes the rise in AD to reduced exposure to various childhood infections and bacterial endotoxins.10, 11
Climate: AD flares occur in extremes of climate. Heat is poorly tolerated, as is extreme cold. A dry atmosphere increases xerosis. Sun exposure improves lesions, but sweating increases pruritus. These external factors act as irritants or allergens, ultimately setting up an inflammatory cascade.
Food antigens: The role of food antigens in the pathogenesis of AD is controversial, both in the prevention of AD and by the withdrawal of foods in persons with established AD. Most reported studies have methodologic flaws. Because of the controversy regarding the role of food in AD, most physicians do not withdraw food from the diet. Nevertheless, acute food reactions (urticaria and anaphylaxis) are commonly encountered in children with AD.
Probiotics12: The role of probiotics in the diet of patients with AD remains controversial
Aeroallergens: A role for aeroallergens and house dust mites has been proposed, but this awaits further corroboration.