Atopic dermatitis

Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin condition that most commonly manifests in early childhood and can persist into adulthood. Risk factors include a personal and/or family history of atopy, genetic mutations in the filaggrin gene, and environmental factors. Major clinical features include a chronic and/or relapsing course, intense pruritus, and typical eczematous skin lesions that follow age-specific distribution patterns (e.g., face and extensor surfaces in infants and flexural surfaces and creases in older individuals). Triggers (e.g., dust mites, heat, dry climate, skin irritation) can exacerbate and/or induce flares. The diagnosis is typically made clinically. Diagnostic studies are reserved for diagnostic uncertainty, a suspected allergic trigger, and/or a suspected alternative diagnosis. Management is based on AD severity and comprises supportive skin care for AD, trigger avoidance, topical pharmacological treatment (e.g., corticosteroids, calcineurin inhibitors), and advanced dermatology treatments (e.g., topical Janus kinase inhibitors, systemic pharmacological treatment). Exclusive breastfeeding for the first 3–4 months may decrease the risk of developing AD.

• Prevalence: Approx. 8–12% of children and 6–9% of adults are affected. ^[1][2][3]
• Age of onset: typically before 1 year of age ^[4]

Epidemiological data refers to the US, unless otherwise specified.

The etiology of AD is not completely understood.

Risk factors for AD

• Atopy (personal and/or family history) ; ^[5][6]
  • Atopic triad: a triad of asthma, allergic rhinitis, and atopic dermatitis linked to allergen-triggered IgE-mast cell activation
  • Food allergies ^[5]
  • Urticaria
• Genetic factors: 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. ^[5][6]
• Environmental factors
  • Living in an urban setting ^[3][5]
  • Living in a region with low UV-light exposure ^[6][7]
  • Small family size (may be related to low microbial exposure in childhood) ^[3][5]

Genetic risk factors are strongly associated with AD. ^[3][5]

Triggers for AD ^[3]

• Environmental allergens
  • Dust mites ^[5]
  • Animal dander
  • Pollen
• Environmental conditions
  • Heat
  • Dry or humid climate
• Stress
• Skin irritation
• Air pollutants (e.g., particulate matter, nitrogen oxide, carbon monoxide) ^[8]

Triggers can induce AD flares. ^[3][5]

Multiple complex mechanisms are involved in the manifestation of AD, but the pathophysiology is not fully understood. ^[9][10]

• Epidermal barrier dysfunction (due to filaggrin deficiency and decreased ceramide levels) → loss of moisture (i.e., transepidermal water loss) → 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

Major features of AD ^{[4][5][11][12]}

• Pruritus
  • Often the most bothersome symptom
  • Frequently triggers an itch-scratch cycle
• Chronic and/or relapsing course
  • Symptoms fluctuate over time (e.g., alternating periods of flares and remission).
  • Typically begins in childhood and may persist for years
• Eczematous skin lesions
  • AD in lightly pigmented skin: erythematous or skin-colored dry patches and/or plaques
  • AD in skin of color ^[4][13][14]
    • Less visible erythema; possibly skin-colored, violaceous, or brown papules, patches, or plaques ^[6]
    • Commonly manifests as follicular eczema: rough, dry papules, often uniformly spaced around the hair follicles within the affected area
    • Prominent postinflammatory pigmentation changes
    • Increased severity ^[4]
  • Cutaneous findings of chronic involvement: circumscribed lesions, lichenification, fissures
• Age-specific distribution patterns
  • Infantile AD (age < 1 year) ^[5][6][12]
    • Face (especially the cheeks), scalp, and neck
    • Extensor surfaces of the extremities
    • Trunk
    • Typically spares the diaper area
  • Adults and children ^[15]
    • Flexural surfaces of the extremities and flexural creases (e.g., antecubital fossa, popliteal fossa, ankles, wrists) ^[12]
    • Adolescents and adults: hands and feet often involved ^[6]

Atopic dermatitis rarely affects the diaper area due to the diaper’s occlusive nature and the increased moisture in this region. ^[16]

Features suggestive of AD ^{[4][5][11][12]}

• Onset typically < 12 months of age ^[17]
• Personal and/or family history of atopy
• Xerosis
• See “Complications of AD” for nonspecific comorbidities and complications.

Clinical diagnosis ^[5][11][17]

• There are no set diagnostic criteria for atopic dermatitis.
• The presence of major features of AD with or without supportive findings of AD is typically sufficient.

Indications for diagnostic testing ^[5][11][12]

• Clinical uncertainty: A dermatologist may perform a skin biopsy to identify findings suggestive of AD and exclude alternative conditions. ^[2][17]
  • Acute AD findings: spongiotic dermatitis and perivascular infiltration of lymphocytes, macrophages, eosinophils, and dendritic cells
  • Chronic AD findings: epidermal thickening and hypertrophy
• Suspected allergic triggers (e.g., dust mite allergy, pet allergy, food allergy)
  • Skin prick testing
  • Allergen-specific IgE testing
• Exclusion of suspected differential diagnoses of AD
  • Fungal infection: KOH test
  • Allergic contact dermatitis: patch test

Routine allergy testing is not recommended; consider allergy testing based on clinical history of triggers and/or persistent moderate-to-severe AD symptoms despite treatment. ^[11]

If allergy testing is indicated, do not check total serum IgE as it is nonspecific for atopic dermatitis, and IgE levels do not correlate with AD severity. ^[11]

• Seborrheic dermatitis: Lesions are usually dry in atopic dermatitis and greasy in seborrheic dermatitis. ^[18]
• Psoriasis ^[19]
  • 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 ^[20]
  • Contact dermatitis (e.g., allergic contact eczema)
  • Nummular dermatitis
• Infections and infestations ^[19]
  • Mycoses
  • Scabies
• Other
  • Photosensitivity
  • Cutaneous T-cell lymphoma

The differential diagnoses listed here are not exhaustive.

Approach ^{[4][11][12][21]}

• For active lesions, initiate appropriate AD flare management.
• Educate patients and caregivers on the chronic nature of AD and the need for ongoing maintenance management of AD.
• Pruritus not controlled with appropriate AD management: Consider oral antihistamines.
  • Children (off-label for isolated pruritus) or individuals with comorbid allergic conditions : an oral second-generation antihistamine, e.g., cetirizine ^[4]
  • Adults with pruritus that causes sleep loss: Consider an oral sedating first-generation antihistamine, e.g., diphenhydramine (off-label) , hydroxyzine. ^[4][12]
• Assess for indications for specialist referral for AD and refer if indicated.
• Provide a written atopic dermatitis action plan (see “Tips and links” for examples). ^[4][11][12]

AD flare management^{[4][11][12][17][21]}

• Choose a topical treatment based on AD severity, affected body areas, and lesion thickness.
• Reassess response frequently.
• Resolution not achieved with appropriate management (e.g., within 7 days) ^[22]
  • Assess treatment adherence.
  • Adjust topical pharmacological treatment, e.g.:
    • Increase potency of topical corticosteroids (TCS).
    • Consider alternative topical agents (e.g., topical calcineurin inhibitors, topical PDE4 inhibitors).
  • Consider secondary infection or alternative diagnoses.
  • Consider referral.

Consider using scoring tools (e.g., SCORAD index) to determine disease severity and guide management. ^[4][11][12]

Maintenance management of AD ^{[4][11][12][21]}

• All patients
  • Continue general skin care for AD.
  • Regularly reassess for triggers of AD and, if present, provide appropriate management (e.g., avoidance, immunotherapy).
• Individuals with frequent recurrences in a particular area: Initiate proactive therapy with a mid-potency TCS or a TCI twice a week. ^[4][11][12]
• Individuals with refractory moderate or severe AD: Long-term advanced therapies (e.g., UV phototherapy, systemic biologics) may be required to maintain remission.

Indications for specialist referral for AD ^[4][12][17]

Refer to a specialist (e.g., dermatology, allergy and immunology) for any of the following:

• Diagnostic uncertainty
• Consideration of advanced treatment options
  • Poor response to nonpharmacological management and common topical pharmacological treatments
  • Severe AD
  • Significant cosmetic or functional concerns
  • Limited treatment options (e.g., involvement of sensitive areas, adverse effects of corticosteroid therapy)
• Complications of AD (e.g., eczema herpeticum) that require specialist management
• Concern for a congenital immunodeficiency (e.g., Hyper IgE syndrome, Wiskott-Aldrich syndrome), e.g.: ^[11]
  • Infants with severe AD, especially if refractory to treatment
  • Systemic symptoms (e.g., failure to thrive, signs of malabsorption, severe and/or recurrent infections)

Skin care for AD ^[4][11][12]

Advise the patient and/or caregiver of the following:

• Bathe once daily for 5–10 minutes using hypoallergenic cleansers. ^[4][12]
• Pat the skin with a towel after bathing.
• Apply an over-the-counter fragrance-free emollient at least 1–2 times daily, ideally within 3 minutes after bathing. ^[4][11][12]
• Avoid scratching the affected skin to avoid perpetuating an itch-scratch cycle.

Elimination diets are not recommended for atopic dermatitis of any severity. ^[11]

Topical antihistamines are not recommended for pruritus due to an increased risk for adverse effects (e.g., contact dermatitis). ^[12]

Wet wrap therapy ^{[4][11][12][21]}

• Indications: considered for acute flares of refractory moderate-to-severe AD
• Method
  • Apply an emollient with or without a low or mid-potency TCS to the affected area.
  • Cover with a moistened bandage (e.g., cotton, gauze) and wrap with a dry bandage.
  • Reapply a new bandage at least once daily.

Do not use high-potency TCS or ultra-high potency TCS under occlusive dressings (e.g., wet wraps). Check FDA labels for additional information. ^[11]

Dilute bleach baths ^{[4][11][12][21]}

• Indications: considered for moderate-to-severe AD maintenance to improve severity and prevent flares
• Mechanism: anti-inflammatory effects
• Method
  • Add one-half cup of 6% liquid bleach to 40 gallons of lukewarm water (a full standard-size bathtub). ^[4][12]
  • Soak in the 0.005% sodium hypochlorite solution for 10 minutes 2–3 times per week. ^[4][12]

Topical corticosteroids (TCS) ^{[4][11][17][25]}

• Indications
  • AD flare management
  • Proactive therapy
• Follow the general principles of TCS, e.g.:
  • Choose a TCS based on AD severity, affected body areas, and thickness of skin/lesions.
  • Use the lowest effective potency for the shortest amount of time.
    • Mid-potency or high-potency TCS: Use less frequently (e.g., once daily) than low-potency TCS. ^[11]
    • TCS for proactive therapy: Use a mid-potency TCS once daily for two consecutive days per week. ^[11]
• Drug options: See “Overview of TCS” for examples by potency and indications.

Nonsteroidal topical pharmacological treatment ^{[4][11][17][21]}

The following options are commonly considered for individuals who do not respond to or cannot use TCS.

Topical calcineurin inhibitors (TCIs)

• Indications
  • AD flares (particularly in sensitive areas)
  • Proactive therapy
• Drug options
  • Moderate-to-severe AD in individuals ≥ 2 years: tacrolimus ^[4][11]
  • Mild-to-moderate AD in individuals ≥ 2 years: pimecrolimus ^[4][11][12]

Topical PDE4 inhibitors

• Indications: mild-to-moderate AD flares
• Drug options
  • Adults and children ≥ 3 months: crisaborole 2% ointment ^[4][21]
  • Adults and children ≥ 6 years: roflumilast 0.15% cream ^[11][21]

For refractory moderate or severe AD, specialists may consider additional treatments, e.g.:

• Advanced topical pharmacological treatments ^{[11][21][24] [4][12]}
  • Topical JAK (JAK) inhibitors (controversial), e.g., ruxolitinib 1.5% cream, delgocitinib 2% cream ^[11][17]
  • Topical aryl hydrocarbon receptor agonists, e.g., tapinarof 1% cream
• Systemic pharmacological treatments^{[11][21][24] [4][12]}
  • Biologics (preferred systemic agent), e.g., dupilumab, tralokinumab, lebrikizumab, nemolizumab
  • JAK inhibitors, e.g., upadacitinib, abrocitinib, baricitinib
  • Cyclosporine ^[11]
  • Oral corticosteroids (controversial) ^[11][12]
• Other ^{[4][11][12][21][24]}
  • Phototherapy (UVB light)
  • Allergen immunotherapy

Common comorbidities ^[4][11][12]

• Other atopic conditions (e.g., allergic rhinitis, asthma)
• Periorbital features of chronic atopy
  • Hertoghe sign
  • Dennie-Morgan fold: pronounced skin folds below the eye
  • Allergic shiners
• Immune-mediated conditions (e.g., alopecia areata)
• Keratosis pilaris
• Ichthyosis vulgaris
• Hyperlinear palms
• Lip dermatitis (e.g., eczematous cheilitis)
• Pityriasis alba
• Dermatographism
• White dermographism: transient blanching of skin after skin stroking
  • Caused by cutaneous vasoconstriction
  • Normal variant, but more common in patients with atopic dermatitis
• Nummular dermatitis
• ↑ Serum IgE (if discovered incidentally)

Complications ^[4][11][12]

• Self-induced secondary lesions
  • Excoriations and/or hemorrhagic crusts
  • Lichenification
  • Prurigo nodularis
• Secondary infections
  • Bacterial: skin and soft tissue infections (e.g., impetigo, staphylococcal skin infections)
  • Viral: eczema herpeticum , molluscum contagiousum
  • Fungal: tinea (especially Trichophyton rubrum)
• Post-inflammatory skin changes
  • Hypopigmentation
  • Hyperpigmentation
• Ocular conditions
  • Recurrent keratoconjunctivitis
  • Cataracts
  • Keratoconus
• Psychosocial conditions
  • Sleep disturbances
  • Decreased quality of life
  • Depression
  • Anxiety
• Treatment-associated conditions
  • Osteoporosis
  • Bone fracture

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.

Exclusive breastfeeding for the first 3–4 months may decrease the risk of developing AD. ^[26][27]