Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory skin condition associated with a relapsing and remitting course. It is characterized by xerosis, pruritus, and erythematous papules coalescing into plaques and may include secondary changes of weeping, scaling, and lichenification. The condition is associated with other atopic conditions in the patient (or within the family) such as food allergies, allergic rhinitis, and asthma.

Atopic dermatitis is thought to affect up to 25% of children in the United States, making it the most common inflammatory skin disease of early childhood. Sixty percent of affected children develop symptoms by the age of 1 year and 90% present by the age of 5 years. Atopic dermatitis is a cause of significant psychosocial distress and can have a negative effect on quality of life. The economic burden of atopic dermatitis in the United States is estimated at more than five billion dollars annually.

The majority of patients with atopic dermatitis outgrow the condition by adulthood. Features associated with persistent disease include early onset, severe phenotype, the presence of other atopic conditions, and family history of atopic dermatitis.

Pathophysiology

Atopic dermatitis is primarily a disorder of impaired skin-barrier function and immune dysfunction. The pathophysiology is complex, with contributions from both genetic and environmental factors.

From a genetic perspective, the most important gene identified as likely contributing to the pathophysiology is the filaggrin gene (FLG), which encodes the epidermal protein filaggrin. More than 40 different mutations have been described, and reductions in the filaggrin protein are found in patients with moderate-to-severe atopic dermatitis and are hypothesized to contribute to disease via multiple mechanisms:

• reduced ability of skin cells to maintain hydration and restrict water loss

• inadequate barrier function leading to allergen entry

• changes in local pH enable bacterial overgrowth

(Adapted from: Filaggrin Mutations Associated with Skin and Allergic Diseases. N Engl J Med 2011.)

Age-Related Phases

The three distinct age-related phases of atopic dermatitis are infantile, childhood, and adult. Different areas are affected in each phase, with some overlap and lesions occurring outside the age-specific distribution.

(Reprinted from Atopic Dermatitis, Lancet 2015. Copyright [2015], with permission from Elsevier.)

(Source: Atopic Dermatitis. N Engl J Med 2021.)

Lesions of early-onset atopic dermatitis involving the cheek and scalp in an infant at 4 months of age; infantile atopic dermatitis often affects scalp, cheeks, forehead and hands. (Source: Atopic Dermatitis. N Engl J Med 2008.)

Involvement of the flexural surfaces in a child; childhood atopic dermatitis affects flexural surfaces, including the antecubital and popliteal fossa. (Source: Atopic Dermatitis. N Engl J Med 2008.)

An acute presentation of atopic dermatitis with erythema and vesicles. (Source: Atopic Dermatitis. N Engl J Med 2005.)

Lichenification, defined as skin thickening with enhancement of skin markings, is a finding in chronic atopic dermatitis. (Source: Atopic Dermatitis. N Engl J Med 2005.)

(Source: Atopic Dermatitis. N Engl J Med 2021.)

Nummular dermatitis in an infant. (Source: Atopic Dermatitis. N Engl J Med 2005.)

Diagnosis

Formal diagnostic criteria for atopic dermatitis are too numerous to be used routinely in clinical practice. The diagnosis of atopic dermatitis is usually based on the presence of the following features:

• Major features (must be present):

  • pruritus

  • eczema following the typical age-specific distribution or chronic/relapsing

• Important features:

  • early onset

  • personal or family history of atopic disease

  • xerosis

• Associated features:

  • Dennie-Morgan folds below the eyelids

  • allergic shiners (periorbital darkening)

  • facial pallor

  • pityriasis alba

  • keratosis pilaris

  • ichthyosis vulgaris

  • hyperlinearity of the palms

  • milia

  • lichenification

(Source: Photo courtesy of David Amrol, MD.)

Management

Pillars of atopic dermatitis management:

• repair and maintain a healthy skin barrier

• reduce inflammation

• alleviate pruritus

• treat and prevent infection

Tips for maintaining a healthy skin barrier:

• avoid irritants and allergic triggers

• bathe for <10 minutes and avoid hot water

• use mild soap and cleanser only as needed

• use ointments instead of creams and lotions

• apply ointments and moisturizers immediately after bathing

Topical Treatment

• Topical glucocorticoids are considered the first-line treatment for active atopic dermatitis. When used in the right potency for the appropriate amount of time they lead to excellent control of symptoms. They are formulated in a variety of strengths ranging from low-potency class VII to high-potency class I. The least potent preparation necessary should be used for the shortest time possible to avoid unwanted adverse effects, including skin atrophy, telangiectasia, acne, and stretch marks; however, it is also important to avoid undertreatment due to excessive caution. Noncutaneous adverse effects include systemic absorption leading to adrenal suppression, cataracts or glaucoma, and periorificial dermatitis.

• “Wet wrap” therapy may be used to augment the efficacy of topical medications via enhanced absorption. This requires the application of the topical medication or emollient followed by a wet layer of cotton pajamas or dressings and then a second, dry layer. You can find additional information about wet wrap therapy provided by the National Eczema Association.

• Topical calcineurin inhibitors are a complementary treatment to topical glucocorticoids and often used for treatment of recalcitrant atopic dermatitis because they do not cause skin atrophy or other cutaneous adverse effects. They are particularly useful in thin-skinned areas such as the face and intertriginous sites. In the United States, topical calcineurin inhibitors are indicated for use as second-line therapy in patients with atopic dermatitis who have failed other topical prescription treatments or when those treatments are not advisable. They are considered safe for use on the face, including around the eyes, and intertriginous areas and do not cause thinning of the skin. The main adverse effect is burning upon application. The FDA added a black-box warning on topical calcineurin inhibitors because of the potential link between these medications and risk for lymphoma and skin cancer based on animal studies and case reports. Overall, concern for systemic absorption is low. Topical calcineurin inhibitors have been used for many years and have not been linked with increased risk of malignancy in children.

  • Tacrolimus is available in 0.03% and 0.1% ointment preparations. Tacrolimus 0.03% ointment is approved for use in children aged ≥2 years, and tacrolimus 0.1% ointment is approved for use in children aged ≥16 years.

  • Pimecrolimus is available as a 1% cream and is approved for use in children aged ≥2 years.

• Crisaborole 2% ointment is another nonglucocorticoid alternative topical medication that is approved for treatment of mild-to-moderate atopic dermatitis in patients aged ≥3 months. This anti-inflammatory ointment acts by inhibiting phosphodiesterase type 4 (PDE-4). The main adverse effect is stinging and burning.

• Ruxolitinib 1.5% cream is a Janus kinase (JAK) inhibitor approved for use in children aged ≥12 years. The most common adverse effects are burning and pruritus at the application site, headache, and upper respiratory infection. The application area should not exceed 20% of the body surface area. Long-term safety data are lacking along, including the potential adverse effects from systemic absorption. Topical ruxolitinib carries the same boxed warning as the oral JAK inhibitors (risk for serious infections, major cardiovascular events, thrombosis, malignancies, and all-cause mortality) but these adverse events have not been shown in this patient population.

Treatment of Refractory Disease

Patients with severe disease not controlled by topical glucocorticoids and calcineurin inhibitors may require systemic immunosuppressive therapy or ultraviolet light treatment (e.g., narrow-band ultraviolet B [UVB]). Generally, systemic glucocorticoids are avoided because of the risk of flaring with discontinuation and potential adverse effects associated with long-term use.

Agents used for the treatment of refractory atopic dermatitis:

• dupilumab (a subcutaneous injectable interleukin [IL]-4 and IL-13 receptor-alpha antagonist for treatment in patients aged ≥6 months with moderate-to-severe atopic dermatitis not controlled by topical prescription therapies)

• methotrexate

• azathioprine

• mycophenolate mofetil

• cyclosporine

• JAK inhibitors

See Figure1: Summary of the Recommendations for Atopic Dermatitis Therapeutic Management for Pediatric Providers for a diagnostic and treatment model based on treatment guidelines for primary care providers.

See Atopic Dermatitis: Skin-Directed Management for an overview of skin-directed management.

Infection: If acute infection is suspected based on the presence of honey-colored crusting, oozing, pustules, or cellulitis, bacterial cultures may help identify the causative organism. Topical or systemic antibiotics can be used to treat active infection depending on the severity.

Children with atopic dermatitis are also prone to viral superinfection such as herpes simplex virus (eczema herpeticum), molluscum contagiosum, and warts due to the impaired skin barrier.

An 8-year-old girl with atopic dermatitis presented with a 3-day history of a diffuse eruption of pruritic, umbilicated, erythematous vesicles with erosion and crusting on the flexor surfaces of the legs. (Source: Eczema Herpeticum. N Engl J Med 2017.)

Dilute bleach baths can be used to treat superinfection with Staphylococcus aureus and maintain remission from flares. Commercially available sodium hypochlorite-containing washes may be preferred by patients and families. Increasing evidence suggests that bleach baths may have anti-inflammatory and antipruritogenic properties. S. aureus decolonization can be attempted with the use of intranasal mupirocin.

Pruritus: The mainstay of treatment for pruritus is to control the atopic dermatitis with topical glucocorticoids. The pruritus associated with atopic dermatitis is not histamine-mediated and is primarily managed by treating the underlying dermatitis. However, oral antihistamines, such as hydroxyzine and diphenhydramine, can be considered for patients who complain of associated sleep disturbance. There is limited evidence to suggest that oral antihistamines or melatonin can be used for sedative effects to minimize sleep disturbance due to the pruritus.