Atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease that typically manifests for the first time in early childhood. Although it often improves during adolescence, it may also become a chronic condition that extends into adulthood. Atopic dermatitis is often associated with other atopic diseases, such as asthma or allergic rhinitis. Although the underlying etiology is not completely understood, genetic components, as well as exogenous and endogenous triggers, are believed to play a role. The main symptoms of atopic dermatitis are severe pruritus and dry skin. Initial management of atopic dermatitis involves avoiding flare triggers and moisturizing the skin. Topical steroids and calcineurin inhibitors may be added if symptoms persist. In refractory and severe cases, phototherapy or systemic therapy with immunomodulating medications may be used. The most common complication of atopic dermatitis is the development of secondary infections; psychosocial complications may also arise.

• Prevalence: Approx. 8–12% of children and 6–9% of adults are affected. ^[1][2][3]
• Age ^[2][3]
  • Onset of symptoms usually occurs at 3–6 months of age.
  • Disease often improves with age.

Epidemiological data refers to the US, unless otherwise specified.

Although the etiology of AD is not completely understood, genetic factors have been shown to play a role in its development. Certain social and environmental risk factors are believed to be associated with AD, but the evidence is inconclusive. Exogenous and endogenous triggers can induce flares of AD. ^[2][4][5]

• Genetic risk factors
  • Approx. 70% of affected individuals have a family history of atopy (e.g., eczema, asthma, and/or allergies) ^[6]
  • Loss-of-function mutations in the FLG gene lead to a deficiency of filaggrin, an epidermal protein that plays a role in the skin's barrier function. ^[4]
• Social and environmental risk factors
  • Low microbial exposure in early childhood
  • Living in an urban setting
  • Living in a region with low UV-light exposure
  • Diet high in sugars and unsaturated fatty acids
  • Repeated exposure to antibiotics in childhood (< 5 years of age)
  • Small family size
• Triggers ^[3][6]
  • Dust mites
  • Heat
  • Extremely dry or humid climate
  • Stress
  • Skin irritation
  • Air pollutants (e.g., benzene, nitrogen oxide, carbon monoxide)
  • Pollen
  • Fur from pets or other animals

The most important risk factors in the development of atopic dermatitis are a family history of atopy and mutations in the FLG gene.

Multiple complex mechanisms are involved in the manifestation of AD, but the pathophysiology is not fully understood. ^[4][5]

• Epidermal barrier dysfunction (due to filaggrin deficiency and decreased ceramide levels) → loss of moisture → dry skin
  • Increased water loss
  • Microbiome imbalance
  • Increased risk of secondary infections
  • Triggering of inflammatory processes
  • Increased skin pH
  • Immune cell infiltration
• Inflammation of the skin → severe pruritus
  • Promotion of IgE-mediated hypersensitivity
  • Triggering of epidermal barrier dysfunction
  • Increased T-cell infiltration
  • Imbalance of Th2 to Th1 cytokines
  • Increased Th2-cell-mediated response
  • Increased antigen presentation
  • Imbalance in genetic expression of regulatory and inflammatory protein

• Main symptoms: intense pruritus and dry skin
• Infantile AD (age < 2 years) ^[7][8]
  • Eczema involving the face, head, and extensor surfaces of the extremities that usually spares the diaper area
  • May present initially with features similar to seborrheic dermatitis, e.g., cradle cap ^[9][10][11]
  • Dennie-Morgan fold: increased folds below the eye
  • Occasionally, lesions appear on the trunk.
• Childhood AD (age 2–12 years) ^[8]
  • Eczema: flexural creases (antecubital fossa and popliteal fossa), skin folds, extensor surface of hands
  • Lesions usually become lichenified (thickening of the skin with accentuated skin markings).
• Adult/adolescent AD (age > 12 years) ^[7]
  • Lichenified lesions and pruritus of flexor surfaces of the extremities
  • Antecubital fossae are frequently involved.
  • Adult AD may also present as nummular eczema.
• Associated skin findings in AD ^[8][12][13]
  • Atopic triad: a triad of asthma, allergic rhinitis, and atopic dermatitis that is linked to allergen-triggered IgE-mast cell activation
  • Food allergies
  • Keratosis pilaris: keratinized hair follicles (rough bumps) typically distributed over extensor arms and thighs
  • Xerosis
  • Dermatographism: formation of urticaria after minor pressure is applied to the skin, likely mediated by local histamine release
  • White dermographism: transient blanching of skin after skin stroking
    • Caused by cutaneous vasoconstriction
    • Normal variant, but more common in patients with atopic dermatitis
  • Hertoghe sign: thinning or loss of the outer third of the eyebrows

The symptoms of atopic dermatitis are variable and often change in the course of a lifetime. Pruritus and dry skin are usually the main symptoms.

Diagnostic criteria ^[6]

• Required for diagnosis
  • Pruritus
  • Eczema (acute, subacute, or chronic)
    • Typical morphology and age-specific distribution patterns (see “Clinical features”)
    • Chronic or relapsing course
  • Exclusion of other conditions with similar appearance (see “Differential diagnoses”)
• Additional findings
  • Early age of onset
  • Atopy
    • Personal and/or family history
    • Immunoglobulin E reactivity (↑ serum IgE)
    • Comorbid atopic diseases (i.e., asthma, allergic rhinitis, allergic conjunctivitis, and food allergies)
  • Xerosis
  • Other associated skin findings in AD

Atopic dermatitis is a clinical diagnosis. Other conditions with a similar appearance should be excluded, e.g., seborrheic dermatitis, psoriasis, other eczematous diseases, or skin infections.

Severity assessment ^[6][14][15]

• AD is often stratified by severity for practical purposes (e.g., mild, moderate, severe).
• There is no accepted gold standard classification system for clinical practice.
• An individual multifactorial assessment is recommended and includes the following:
  • Estimated body surface area involved
  • Clinical features of lesions (e.g., crusting, oozing, redness, swelling)
  • Identification of lesions in areas of greater sensitivity, visibility, or functional importance (e.g., palms, soles, face, neck, genitals, joints)
  • Functional and psychosocial impact of symptoms (e.g., degree of pruritus, sleep disturbance)
• Consider supplementing this assessment with the focused use of scoring systems. ^[14]

Other investigations ^[2]

• Allergy testing: limited evaluation for food allergens (i.e., peanut, soy, cow's milk, wheat) ^[16]
  • Consider in children < 5 years old with moderate-to-severe AD and any of the following:
    • Symptoms refractory to optimal management and topical pharmacotherapy
    • Clear history of a specific food-induced allergic reaction
• Histopathology
  • Not routinely indicated; can be obtained to help rule out alternate diagnoses
  • Supportive findings
    • Spongiotic dermatitis: epidermal intercellular edema
    • Perivascular infiltration of lymphocytes, macrophages, eosinophils, and dendritic cells
    • Epidermal thickening and hypertrophy are seen in chronic eczema.

• Seborrheic dermatitis: Lesions are usually dry in atopic dermatitis and greasy in seborrheic dermatitis. ^[17]
• Psoriasis ^[8]
  • Onset is generally after adolescence.
  • Lesions are typically covered with white or silvery scales and are commonly located on the extensor surface of extremities.
• Other eczematous diseases ^[18]
  • Contact dermatitis (e.g., allergic contact eczema)
  • Nummular dermatitis
• Infections and infestations ^[8]
  • Mycoses
  • Scabies
• Other
  • Photosensitivity
  • Cutaneous T-cell lymphoma

The differential diagnoses listed here are not exhaustive.

Approach

Nonpharmacological therapy ^[16][18][19]

• Avoid triggers of flares: See “Triggers” in “Etiology” section above.
• Maintain skin hydration
  • Emollients
  • Regular bathing is recommended. ^[19]
    • Consider bathing up to once daily for short periods of time (e.g., 5–10 minutes).
    • Hypoallergenic cleansers can be used, but with limited frequency.
    • Apply emollients shortly after bathing.
  • For severe or refractory cases: consider wet wrap therapy
    • A moistened bandage is applied with emollients or topical corticosteroids to the affected area.
    • A dry outer bandage is applied around the inner moist bandage.
• Stress management: to help cope with the impact of AD on daily life (e.g., supportive psychotherapy) ^[18]

Topical pharmacotherapy ^[16][19]

• Topical corticosteroids (first-line)
  • Indications
    • During disease flares until skin lesions improve
    • Continued use for flare prevention for patients with frequent, recurrent flares at the same site
  • Available agents
    • Low-potency: e.g., hydrocortisone 1%
    • Medium-potency: e.g., triamcinolone 0.1%
    • High-potency: e.g., fluocinonide 0.05%
• Topical calcineurin inhibitors (second-line)
  • Indications
    • Poor response to topical steroids
    • Side effects from topical steroids
    • As steroid-sparing agents
    • Consider as initial treatment for sensitive skin areas.
  • Available agents
    • Moderate-to-severe AD: Tacrolimus
    • Mild-to-moderate AD: Pimecrolimus
• Topical antimicrobials
  • Not routinely indicated
  • Consider bleach baths and intranasal mupirocin for moderate to severe disease with signs of bacterial infection.

Topical antihistamines are not recommended for the treatment of AD due to a lack of benefit and potential for local side effects. ^[19]

The potency of the topical corticosteroid used should be guided by patient factors (e.g., affected areas of the body, age) and disease severity.

Systemic therapy ^[16][20]

These advanced therapies should be administered in consultation with a specialist.

• Common indications
  • Failure of topical treatment to control symptoms during a flare
  • Maintenance therapy for chronic atopic dermatitis with recurrences despite topical pharmacotherapy
• Treatment options
  • Phototherapy (UV light)
  • Noncorticosteroid systemic immunomodulating medications
    • Available agents
      • Cyclosporine
      • Azathioprine
      • Methotrexate
      • Alternative agents: mycophenolate mofetil, interferon-γ, dupilumab ^[23]
  • Systemic corticosteroids
    • Rarely indicated; may be considered for severe cases as bridge therapy
    • Can cause rebound flares when discontinued
  • Experimental therapies: several biologics, small molecule agents, and other topical treatments are undergoing assessment in clinical trials, with an emphasis on their antiinflammatory and antipruritic effects. ^[4]

The optimal dosing, duration, and monitoring of systemic immunomodulatory therapy are unclear. Treatment should be tailored to the patient and made in consultation with a specialist. ^[20]Systemic steroids should only be used sparingly in AD due to side effects of corticosteroid therapy and the risk of rebound flares after discontinuation. ^[20]

• Secondary infections
  • Bacterial: staphylococcal skin infections ^[24]
  • Viral: eczema herpeticum ^[25]
  • Fungal: tinea (especially Trichophyton rubrum)
• Psychosocial complications ^[3]
  • Sleep disturbances
  • Decreased quality of life

We list the most important complications. The selection is not exhaustive.

The symptoms of atopic dermatitis usually improve with age and often resolve completely after puberty. ^[2]