Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease in childhood, affecting up to 17% of children in the United States. This skin disease is characterized by intense puritus and cutaneous inflammation. The quality of life of affected individuals can be significantly affected, particularly in those with moderate to severe disease.

In addition, AD patients are predisposed to a variety of skin infections, including Staphylococcus aureus and herpes simplex virus. Up to 50% of children with AD go on to develop asthma. AD also carries with it a significant financial burden to the family and society.

The pathogenesis of AD is complex, involving genetic factors, skin barrier defects, and immune dysregulation (reviewed in reference). The genetics of AD is an area of intense research. Genetic polymorphisms have been associated with chromosome 5q22-23, which contains a cluster of T helper type 2 (Th2) cytokine genes (IL-4 and IL-13).

Those genes play a significant role in IgE production and allergic sensitization. More recently, the association of AD with filaggrin gene mutations has pointed to the role of skin barrier defects in the pathogenesis of AD. Filaggrin is a protein essential to the normal barrier function of the skin.

Deficiency in this protein may contribute to the physical barrier defects in AD and predispose patients to increased transepidermal water loss, infections, and inflammation associated with exposure of cutaneous immune cells to allergens. A recent study showed that the level of filaggrin can be modulated by cytokines.

This may present specific therapeutic opportunities, although, at this time, maintaining a normal epidermal barrier is key. There is currently no diagnostic laboratory test for AD. Although the majority of AD patients have elevated total serum IgE, up to 30% of these patients have normal total serum IgE and show no allergic sensitization to food or aeroallergens.

The diagnosis of AD is based on clinical criteria. Itch must be present for the diagnosis of AD. In addition, the patient should have three or more of the following criteria:

  • Visible rashes on the flexural areas (elbows, back of knees, front of neck, or eyelids); in infants, the rash may be present on the cheeks or extensor areas of the knees or elbows.
  • History of rashes on the flexural areas.
  • Personal or family history of respiratory allergies (asthma or allergic rhinitis)
  • History of dry skin in the past year.
  • Onset before 2 years of age.

Ninety percent of AD patients have onset of the disease before 5 years. Therefore, new-onset AD in older children or adults should raise suspicion for other skin conditions. Daily skin care is key in the control of AD symptoms. The following list provides some of practical actions to take in the treatment of AD:

  • Rather than soaps, use cleansers with minimal defatting activity and a neutral pH.
  • Avoid alcohol and astringents in skin care products.
  • Avoid wool clothing or other materials that may be irritating to the skin; cotton or cotton blends are generally preferred.
  • Launder clothing to remove formaldehyde and other chemicals.
  • Use liquid detergents, which are easier to rinse out than powder detergents.
  • Add a second rinse cycle to facilitate further removal of detergents.
  • Avoid extremes of environmental temperatures or humidity; prolonged exposure to sun may lead to overheating and evaporation, as well as perspiration, all of which can be irritating.
  • Use sunscreens with low irritancy potential, such as those made specifically for the face.
  • After swimming, shower with a cleanser to remove chlorine or bromine.
  • Avoid proven allergens.
  • Most importantly, take time for daily skin care with hydration followed by moisturizers.

Skin hydration is best accomplished through daily soaking baths for 10 to 20 minutes. It is important to remind patients and caregivers to apply a topical medication or moisturizer immediately after bathing. This is to seal in the water that has been absorbed into the skin and prevent evaporation that can lead to further drying of the skin.

The combination of skin hydration and the use of a moisturizer may help to reestablish and preserve the skin barrier function. In addition, moisturizers can also decrease the need for topical corticosteroids. Moisturizers are available as ointments, creams, lotions, and oils.

Due to their occlusive nature, ointments are ideal for maintaining skin hydration after bathing or shower, but they may also trap perspiration, resulting in increased pruritus. Therefore, they may be more suitable for use in dry environments or in younger children or infants, who are generally more tolerable of the ‘‘greasy’’ feel.

Lotions and creams, due to added preservatives or fragrances, may have more irritating effects. In addition, lotions contain more water than creams and may therefore have a drying effect through evaporation of their contents from the skin.

Although oils (eg, mineral oil) can be applied easily, they often prove to be less effective moisturizers based on their emollient properties and occasionally irritant potential. Ceramides are lipids important to the barrier function of the skin and are shown to be deficient in AD skin.

The use of a ceramide-dominant emollient has been found to decrease transepidermal water loss and the disease activity of AD in children. Several ceramide-based creams are currently available and a new ceramide-containing cream, Epiceram, is expected to be available in 2007.

In addition, nonsteroidal creams marketed as medical devices (thus requiring prescriptions) include Atopiclair and MimyX. They have unique ingredients, different proposed mechanisms of action, and do not have any restrictions for age or length of application.

Itch is usually the most distressing symptom of AD. Even patients whose AD is under good control may continue to be affected by itch. First-generation antihistamines might be of benefit primarily through their sedating effects at bedtime.

On the other hand, topical antihistamines and analgesics, due to their potential for contact allergy, should be avoided. There is increasing evidence that neuropeptides and opioid receptors are involved in the pathogenesis of itch in AD.

A recent placebocontrolled trial that included patients with AD showed that a cream containing naltrexone, an opioid receptor antagonist, was effective in relieving pruritus. In addition, the study showed that the clinical efficacy of the medication correlated with changes in opiate receptor expression.

Sleep disturbance is a significant problem in AD. Pharmacologic management for sleep disturbances in AD has recently been reviewed. Doxepin is a tricyclic antidepressant with both H1 and H2 receptor antagonist activity and may be helpful to aid the sleep of AD patients.

In addition, doxepin possesses anxiolytic and antidepressant effects, which may be helpful in select AD patients. However, the dose used to help with sedation is generally lower than the dose needed for antidepressant effects, and patients may have difficulty tolerating daytime sedation with higher doses.

Other medications that may improve the sleep of AD patients include benzodiazepine and nonbenzodiazepine hypnotics, chloral hydrate, and clonidine. However, there are limited data on the use of these medications in AD. Therefore, potential risks and benefits of these medications need to be considered.