Key points

Video of Pruritus in atopic dermatitis accompanies this article at http://www.pediatric.theclinics.com/

Overview

Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterized by intense pruritus and a waxing and waning course. This condition most often presents in infancy and childhood and can persist, in one form or another, throughout adulthood. The exact cause of AD is unknown, but it likely reflects an interplay between genetic and environmental factors. AD affects up to 20% of children in the United States, and the prevalence may be increasing. Treatment can be very effective in alleviating symptoms but serves only to manage the disease, not cure it. Appropriate therapy can also prevent significant complications, such as infection, sleep disturbance, behavioral problems, and growth impairment.

Epidemiology

Population studies have demonstrated an increasing prevalence of AD throughout the world. In the United States, it affects approximately 10% to 20% of children younger than 18 years, and these numbers are rising. Affected children are more likely to be black, urban, and living in homes with higher education levels. As a chronic disease, AD has a significant impact on health care resource utilization, similar to asthma or diabetes. There were an estimated 7.4 million outpatient physician visits for AD during the 7-year-period between 1997 and 2004, amounting to an estimated health care cost of US $364 million to $3.8 billion annually.

Epidemiology

Population studies have demonstrated an increasing prevalence of AD throughout the world. In the United States, it affects approximately 10% to 20% of children younger than 18 years, and these numbers are rising. Affected children are more likely to be black, urban, and living in homes with higher education levels. As a chronic disease, AD has a significant impact on health care resource utilization, similar to asthma or diabetes. There were an estimated 7.4 million outpatient physician visits for AD during the 7-year-period between 1997 and 2004, amounting to an estimated health care cost of US $364 million to $3.8 billion annually.

Pathophysiology

The exact cause of AD is unknown. However, it is generally agreed that AD results from a combination of genetic and environmental factors. Twin studies support a high rate of concordance; identical twins have a 7-fold increased risk for AD, and fraternal twins have a 3-fold increased risk.

Healthy skin acts as a barrier to both outside influences and transepidermal water loss. Current theory holds that a genetically compromised barrier allows for penetration of environmental factors (irritants, allergens, and bacteria) with resultant immune dysregulation. A mutation in the filaggrin gene, responsible for an important component of the barrier, can be found in up to 10% of people of European ancestry. Filaggrin is an epidermal protein that acts as waterproof “mortar” between keratinocytes in the outermost layer of the skin. Mutations in this protein cause ichthyosis vulgaris and are positively associated with more severe or persistent AD.

Other prevalent theories of pathogenesis in AD focus on immune dysfunction. One observation in support of the role of immune dysfunction is that many primary immunodeficiency syndromes are characterized by early onset of diffuse eczematous eruptions and are caused by genetic mutations resulting in disruption of various immune functions, such as hyper-immunoglobulin E (IgE) syndrome, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and Omenn syndrome. In the 1980s, a popular theory, termed the “hygiene hypothesis,” emerged in an attempt to explain the fact that atopy tends to affect individuals from developed nations and those in a higher socioeconomic status. This hypothesis asserts that the lack of childhood exposure to infectious agents results in an immune response favoring atopy, whereas early exposure to infectious agents triggers a T helper 1 (T _H 1) response, thus diverting the immune system away from a T helper 2 (T _H 2) “atopic” response. There is somewhat conflicting data in support of this hypothesis, and in truth, the interplay between T _H 1 and T _H 2 is likely more complex than previously thought. More rigorous studies into causation are needed.

Prevention and prognosis

Many studies have investigated primary prevention strategies and their effect on AD. These studies have examined the effect of early exposure to environmental and dietary factors such peanuts, eggs, soy, and animal dander or early supplementation of probiotics, breast milk, and vitamin D as related to development of AD. There is currently no convincing evidence that any of these strategies are helpful.

The natural history of AD is variable. Based on population studies, a significant proportion of affected children “outgrow” the disease, as only 1% to 3% of adults are affected. Patients with the most severe disease are more likely to have persistent disease.

Presentation

Physical Examination

In infants, involvement of the face, neck, and extensor extremities (elbows, knees) is characteristic. Infantile eczema on the cheeks can appear more acute with a pseudovesicular or “weepy” appearance ( Fig. 1 ). This condition is often misdiagnosed as impetigo. Persistent, bright red plaques may develop on the cheeks and chin at the time of teething and introduction of solid food, likely related to chronic irritation from saliva and foods. Infants may also have a more diffuse variant, but often with characteristic sparing of the diaper area. Scalp dermatitis is common and linear excoriations are common at this site, even with minimal skin involvement.

Infantile atopic dermatitis with facial involvement.

( Courtesy of Ronald Hansen, MD, Phoenix, AZ.)

With increasing age, children tend to develop the classic flexural patches and plaques on the antecubital and popliteal fossae ( Fig. 2 ). Hand and foot plantar dermatitis is also quite common ( Fig. 3 ). In more severe cases, thickened plaques are seen on the dorsal hands, feet, and knees, often with a lichenified or leathery appearance, with prominent skin lines ( Figs. 4–6 ) Children with darker skin typically have perifollicular hyperpigmented or hypopigmented rough 1- to 2-mm papules that can coalesce into broad, near-diffuse plaques, most prominent on the extensor surfaces ( Fig. 7 ). This can give the skin a “pebbled” or spotty appearance ( Fig. 8 ). This variant is often termed papular eczema. The nummular variant can be seen on the extremities as coin-shaped crusted or exudative plaques.

Childhood atopic dermatitis with classical involvement of antecubital fossae.

Palmar involvement in atopic dermatitis.

Dorsal foot involvement in atopic dermatitis.

Lichenification in severe atopic dermatitis.

Severe atopic dermatitis of the dorsal hands.

Papular atopic dermatitis.

Diffuse perifollicular atopic dermatitis.

The surrounding skin is often dry and flaky, and there may be platelike ichthyosis of the distal extremities, especially in older children. Postinflammatory hyperpigmentation or hypopigmentation representing prior areas of disease activity is common and more obvious in darker-skinned individuals or those with tanned skin. Excoriations and erosions are nearly universal and are often the result of scratching or an indication of bacterial colonization ( Fig. 9 ).

Excoriations.

Superinfection is common, especially in children with more severe skin disease. Periaurical erosions and fissures overlying eczematous plaques provide a clue to staphylococcal colonization or infection. Isolated or adjacent pustules can be seen. Thick purulent crust, periocular involvement, or punched out ulcerations are often seen in streptococcal infections. Monomorphic punched out ulcers or vesicopustules within eczematous plaques, with or without fever, can indicate a superimposed herpes simplex viral (HSV) infection, more commonly known as eczema herpeticum ( Fig. 10 ).

Eczema herpeticum.

Supporting Features

Other physical examination findings can support the diagnosis of AD. These findings are not specific to AD and can be seen with other atopic disorders or in isolation. One of the most common coexistent conditions is keratosis pilaris, which is common on the upper outer arms and cheeks but can be seen diffusely over the extremities, shoulders, and back ( Fig. 11 ). Ichthyosis vulgaris, often in association with hyperlinear palms, is present in approximately 25% of patients. Many other skin and eye findings are more commonly seen in patients with AD ( Box 1 ).

Keratosis pilaris.

Box 1

Major Features
Pruritus Typical age-specific distribution and morphology Chronic or relapsing dermatitis Personal or family history of atopy
Minor or Associated Features
Xerosis (dry skin) Keratosis pilaris Pityriasis alba Periauricular fissures Ichthyosis and palmar hyperlinearity Susceptibility to cutaneous infections Perifollicular accentuation (dark-skinned patients) Hand and foot dermatitis Scalp dermatitis	Elevated IgE levels Cheilitis Eye findings (conjunctivitis, keratoconus, anterior subcapsular cataracts) Periorbital darkening Dennie-Morgan lines (infraorbital fold)

Diagnosis of atopic dermatitis in children

Data from Hanifin JM, Rajka G. Diagnostic features of atopic eczema. Acta Dermatol Venereol Suppl 1980;92:44–7; and Hanifin JM. Atopic dermatitis in infants and children. Pediatr Dermatol 1991;38(4):763–89.

Differential diagnosis

AD is the most common chronic skin condition seen in children. The distribution and appearance are the most distinguishing features. A family or personal history of atopy supports the diagnosis. There are several clues that should alert the clinician to an alternate diagnosis or a complicating feature of preexisting AD ( Table 1 ).

Workup/Diagnosis

AD is a clinical diagnosis, based on physical findings and supportive history (see Box 1 ).