Atopic Dermatitis

Etiology

Atopic dermatitis has a complex etiology involving both genetic and environmental factors, which contribute to abnormalities in the epidermal barrier and the immune system. It is part of the atopic triad, which also includes allergic rhinitis and asthma. These conditions may develop concurrently or sequentially, in a progression known as the atopic march. Patients with the atopic triad exhibit barrier dysfunction affecting the skin and the upper and lower respiratory tracts, contributing to their clinical manifestations. 

Offspring of parents with atopic disease have a greater than 50% risk of developing atopy if one parent is affected and up to an 80% risk if both parents are affected. Genetic factors include loss-of-function mutations in filaggrin (filament aggregating protein), an epidermal protein involved in maintaining the skin barrier and generating natural moisturizing factor. Filaggrin mutations are present in up to 30% of patients with atopic dermatitis and may also predispose patients to ichthyosis vulgaris, allergic rhinitis, and keratosis pilaris.

Food hypersensitivity also may cause or exacerbate atopic dermatitis in approximately 10% to 30% of patients, with about 90% of reactions or flares attributed to eggs, milk, peanuts, soy, and wheat.[4][5]

Recent studies indicate that there may be an association between smoking and adult-onset atopic dermatitis.

Epidemiology

Atopic dermatitis affects approximately 10% to 30% of children and 2% to 10% of adults in developed countries. The prevalence has increased 2- to 3-fold over the past several decades. The incidence of atopic dermatitis is higher at higher latitudes, which may be related to reduced sun exposure and lower humidity.

Atopic dermatitis is classified into 3 clinical subtypes based on the age of disease onset: early-onset, late-onset, and senile-onset. Early-onset atopic dermatitis (ie, birth to age 2) is the most common subtype, with approximately 60% of cases starting in the first year of life, and about 60% resolving by age 12. In late-onset atopic dermatitis, symptoms begin after puberty. Senile-onset atopic dermatitis is uncommon and manifests in individuals aged 60 or older.

Pathophysiology

Patients with atopic dermatitis exhibit epidermal barrier dysfunction, which increases susceptibility to xerosis, inflammation, pruritus, and other characteristic symptoms triggered by environmental irritants and allergens. Epidermal barrier dysfunction may be partly due to decreased levels of ceramides, key sphingolipids within the stratum corneum that help maintain epidermal barrier function and prevent transepidermal water loss. Dysfunction of the epidermal barrier allows irritants and allergens to penetrate the epidermis and trigger inflammation through an exaggerated T-helper 2 (Th2) immune response. Acute lesions are associated with increased levels of interleukin (IL)-4 and IL-5, whereas chronic lesions demonstrate a Th1-predominant response characterized by elevated interferon-gamma and IL-12.

Scratching further aggravates inflammation by stimulating keratinocytes to release proinflammatory cytokines, including tumor necrosis factor alpha, IL-1, and IL-6. In addition, reduced expression of antimicrobial peptides, such as human beta-defensins and cathelicidins, in the epidermis of patients with atopic dermatitis contributes to increased susceptibility to skin colonization by Staphylococcus aureus, which occurs in more than 90% of patients. Colonization with S aureus can worsen inflammation and lead to secondary infection and impetiginization.[6][7]

In atopic dermatitis, transepidermal water loss is significantly increased, although the underlying cause of epidermal barrier dysfunction is not fully understood. Filaggrin, a protein essential for maintaining epidermal integrity, is often deficient or functionally impaired in affected individuals.

History and Physical

When evaluating a patient with suspected atopic dermatitis, the clinician should obtain a detailed history, with particular attention to the onset and distribution of lesions and the severity of pruritus, including its impact on sleep. The assessment should also include a personal or family history of atopic conditions and evaluation for possible contact allergies. Identification of potential triggers is important and may include exposure to environmental allergens such as dust mites or animal dander; irritants such as soaps, fragrances, or synthetic fabrics like polyester; hot showers or excessive sweating; and food hypersensitivities.

On physical examination, the characteristic findings of atopic dermatitis vary by age group. Infants typically present with edematous papules and plaques that may show vesicles or crust on the scalp, face, and extensor extremities. Although infants may rarely develop atopic dermatitis lesions in the diaper area, they may be susceptible to other causes of diaper dermatitis, such as candidiasis and seborrheic dermatitis.

Children with atopic dermatitis classically present with less exudative patches and plaques involving the antecubital and popliteal fossae. Adults typically present with chronic lichenified lesions with accentuated skin markings, often affecting the hands. Individual lesions may also be classified by stage: acute lesions appear as edematous, erythematous papules and plaques, sometimes with vesicles or crusting; subacute lesions are characterized by erythema, scaling, and variable crusting; and chronic lesions consist of thick plaques with lichenification and scaling.

Evaluation

The diagnosis of atopic dermatitis is typically clinical and based on the characteristic presentation for the patient’s age group and disease subtype. The presence of associated findings, such as keratosis pilaris, may support the diagnosis. When performed, a skin biopsy usually demonstrates an eczematous pattern.

In pediatric cases that are recalcitrant to treatment, fluorescent enzyme immunoassays or skin prick testing may be used to detect IgE antibodies to specific allergens. However, the presence of these antibodies does not always indicate clinically relevant triggers.[8][9]

Treatment / Management

The 4 major components of atopic dermatitis treatment include daily skin care, trigger avoidance, anti-inflammatory therapy, and other complementary modalities.

Daily skin care includes twice-daily application of emollients, ideally within 3 minutes of exiting a lukewarm shower or bath, to prevent skin drying out. However, recent evidence suggests that daily emollient application may not significantly lower the risk of developing atopic dermatitis in newborns.[10] Ointments are the most occlusive vehicle and are less likely to cause burning pain or discomfort during application than other products, such as creams or lotions.(A1)

Topical corticosteroids are first-line agents for the treatment of acute flares and should be applied before emollients to enhance their efficacy. The potency should be sufficient to control the flare promptly, with consideration given to tapering to every-other-day use and then to maintenance therapy twice weekly (for example, on weekends) in commonly affected areas. Potential reversible adverse effects of topical corticosteroids include skin atrophy and telangiectasia.

Sensitive areas of the skin, such as the face and intertriginous regions (eg, the axillae and groin), may require treatment with topical nonsteroidal anti-inflammatory agents, including calcineurin inhibitors such as tacrolimus and pimecrolimus. These agents are commonly used in areas at higher risk for corticosteroid-related adverse effects. Phosphodiesterase 4 inhibitors, such as crisaborole ointment and roflumilast cream, provide additional nonsteroidal options by reducing the production of inflammatory mediators. Roflumilast is approved for use in patients aged 6 and older. Another topical nonsteroidal option is ruxolitinib cream, a Janus kinase inhibitor approved for patients aged 2 and older. This agent reduces inflammatory cytokine signaling and improves pruritus without the risk of skin atrophy associated with topical corticosteroid use.[11][12][13](A1)

When atopic dermatitis is not adequately controlled with topical therapies, systemic treatment options may be considered. These include phototherapy (eg, UVA, UVB, and narrowband UVB phototherapy) and systemic immunosuppressive agents (eg, cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate). In addition, targeted biologic therapies have emerged as effective options for patients with moderate to severe disease. Dupilumab is a monoclonal antibody administered as a subcutaneous injection that blocks the IL-4 receptor, thereby inhibiting the effects of both IL-4 and IL-13. This antibody has the broadest age approval among biologic therapies, with use authorized in children as young as 6 months. Other biologic agents include lebrikizumab and tralokinumab, both IL-13 antagonists approved for use in patients aged 12 and older, with lebrikizumab requiring a minimum body weight of 40 kg. Nemolizumab, an IL-31 receptor antagonist approved for patients aged 12 and older, targets pruritus by inhibiting IL-31–mediated signaling.[14][15][16](A1)

Other complementary therapies include bleach baths (0.5 cup of bleach in a standard 40-gallon bathtub) once or twice weekly to reduce S aureus colonization. Additional strategies may include low-allergen maternal diets during breastfeeding and the use of probiotics and prebiotics in pregnant mothers and at-risk infants. These interventions have been associated with a reduction of up to 50% in the incidence of atopic dermatitis between ages 1 and 4 years compared with placebo.[17][18][19] (A1)

Numerous studies have shown that bleach baths may help relieve the symptoms of atopic dermatitis by reducing the risk of bacterial superinfection; however, other studies have found no benefit. Some patients may benefit from probiotics, which are believed to modulate the immune system and reduce the development of allergen-specific IgE responses.[20]

In patients with suspected food allergies who do not respond to initial treatment despite optimized skin care and topical corticosteroids, food allergy testing using oral food challenge or a trial elimination diet may be considered.

Differential Diagnosis

The differential diagnoses for atopic dermatitis include allergic contact dermatitis, lichen simplex, lichen planus, psoriasis, scabies, tinea infections, and seborrheic dermatitis.

Treatment Planning

Cyclosporine is approved for the treatment of moderate to severe atopic dermatitis in patients aged 16 or older. Therapy should be used with careful monitoring, and intermittent courses of up to 16 weeks are recommended for most patients. Doses should be titrated to minimize renal toxicity, and treatment should be adjusted or discontinued if hypertension or infection develops.

Patients should be educated about the signs of infection and monitored for nonmelanoma skin cancer and elevated serum lipid levels. Concomitant use with phototherapy is not recommended.

Prognosis

Many patients with atopic dermatitis experience improvement over time, although comorbid conditions such as allergic rhinitis and asthma may persist. In some cases of childhood-onset atopic dermatitis, symptoms persist for decades. Atopic dermatitis is characterized by relapsing and remitting flares, with relapses often requiring pharmacologic intervention. Individuals with ongoing exposure to irritants and allergens (eg, tobacco smoke, pet dander, chemical fumes, pollen, soaps, detergents, and wool) may experience persistent symptoms and impaired quality of life.

Persistent and recurrent pruritus is not only bothersome but also contributes to increased healthcare utilization and costs. A recognized complication of atopic dermatitis is Kaposi varicelliform eruption, which results from a primary herpes simplex virus infection (see Image. Kaposi Varicelliform Eruption in a Patient With Atopic Dermatitis). Vesicular lesions typically arise within eczematous skin and may rapidly spread to unaffected areas. Prompt treatment with acyclovir can reduce morbidity.

Complications

Complications of atopic dermatitis include Kaposi varicelliform eruption and secondary bacterial skin infections caused by Staphylococcus and Streptococcus species.