Understanding Atopic Dermatitis

About AD

About atopic dermatitis (AD)

Uncover how atopic dermatitis is a heterogeneous, chronic inflammatory disease driven by immune dysregulation.¹

Burden of disease

AD is a chronic, biologically heterogeneous, inflammatory disease that affects approximately 20% of children, 15% of adolescents, and 10% of adults worldwide.¹

Inflammatory disease

AD is a complex disease defined by contributions from multiple distinct inflammatory pathways, involving both type 2 and non–type 2 inflammation.¹

Symptom presentation

The most burdensome symptom of AD is itch, followed by skin redness, pain, and sleep loss. The continuous demands and care required for AD extends far beyond the skin, affecting patients’ routines and holistic well-being.^2-5

Managing disease progression

The diversity of immune signatures in AD suggests that targeting multiple sources of inflammation may be necessary.^1,6,7

Prevalence and clinical burden of AD

AD prevalence has increased 2-to-3 fold in industrialized nations over the past 50 years. AD affects approximately 16.5 million adults and 9.6 million children in the United States. The age of onset is 60% by age 1 and 90% by age 5 with 25% of adult cases being new-onset. The burden of AD extends beyond visible disease, impacting quality of life and healthcare utilization. While AD ranges in severity from mild to severe, a substantial proportion (~30%) of US adult patients experience moderate-to-severe atopic dermatitis. Disease burden accumulates over time due to persistent inflammation and management demands.^2,4,5,8,9

Chronicity and disease course 

AD is a chronic disease characterized by recurring inflammation causing cycles of flares. While disease activity may fluctuate, inflammation can remain ongoing at different intensities. Chronic inflammation contributes to long-term disease burden in patients with AD.^1,5,10

AD symptoms 

Primary symptoms

Atopic dermatitis (AD) typically presents with pruritus, the most burdensome symptom—relentless, unbearable, and life-altering. Skin manifestations include visible eczematous lesions including dryness, cracking, oozing, burning, and stinging sensations. Chronic or relapsing disease includes painful fissures. These can be unpredictable flares triggered by environmental factors, stress, infections, and irritants.^1,2,4,8,11

Consequential symptoms 

Alongside primary symptoms, AD can impair overall quality of life, affecting sleep, mood, cognitive performance, productivity, and social and financial well‑being. Sleep disruption affects 47% to 60% of patients and rises to 83% during exacerbations, making it a major contributor to reduced quality of life. Patients with AD also demonstrate significantly higher healthcare utilization, including increased outpatient visits, urgent or emergency care use, and hospitalizations.^2,4,5,12

How to recognize and diagnose AD across diverse presentations

AD presentation varies by multiple factors

AD’s broad array of underlying endotypes contributes to the wide variation in clinical features seen among patients, influenced by factors that include disease duration, age, race, ethnicity, and geography. Disease stage also shapes presentation, from acute diffuse lesions to chronic manifestations characterized by thickened skin, scaly, poorly defined plaques, excoriations, and lichenification.^1,6

Symptoms may present differently depending on the age of a patient. Infants typically have lesions present on their face, scalp, and extensors (eg, elbows and knees). In children, lesions typically present on flexures (eg, bends of elbows and behind the knees), while adults may have symptom presentation on flexures, hands, face, or neck.^8,13,14

Skin tone can additionally affect the way symptoms present in a patient with AD. In patients with darker skin, erythema may appear violaceous, purple, brown, or even be difficult to recognize, rather than the classic pink or red seen in lighter skin, which can lead to underestimation of severity and delayed diagnosis. Conventionally, AD presents with pruritic, erythematous plaques and fine scale on the flexural surfaces, while Asian patients often show more well‑demarcated lesions with greater scaling and lichenification. Additionally, individuals of African descent more often exhibit follicular or perifollicular accentuation, papular or lichenoid lesions, and extensor‑predominant involvement, patterns less common in lighter skin types. Post‑inflammatory pigmentary changes—both hyperpigmentation and hypopigmentation—are also more pronounced and more distressing in skin of color, often persisting long after inflammation resolves and contributing substantially to disease burden. Together, these variations demonstrate that skin tone meaningfully influences AD morphology and visibility, underscoring the importance of clinician awareness to avoid misclassification, missed erythema, and underdiagnosis in diverse populations.^15,16

There is an established severity classification for atopic dermatitis which considers the amount of body surface area (BSA) with visible symptoms and impact on quality of life. Mild cases are classified at <16% BSA, moderate cases at 16% and 40% BSA, and severe cases include >40% BSA and significant impairment.^17,18

There are a variety of assessment tools for tracking atopic dermatitis and treatment response, including tools used by clinicians and patients. Clinician tools include the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), and SCORing Atopic Dermatitis (SCORAD). Patient tools include the Patient-Oriented Eczema Measure (POEM), Dermatology Quality of Life Index (DLQI), and itch numerical rating score (NRS).¹⁸

Atopic dermatitis (AD) pathogenesis

Diverse immune pathways contribute to AD heterogeneity

AD is driven by a combination of type 2 and non–type 2 inflammatory pathways, reflecting the disease’s underlying immunologic heterogeneity. While type 2 inflammation—marked by cytokines such as IL‑4 and IL‑13—plays a dominant role across most AD subtypes, additional pathways, including Th1, Th17, and Th22, also contribute, particularly as lesions progress from acute to chronic stages. These overlapping immune signatures create mixed inflammatory profiles that help explain why patients experience varied responses to targeted therapies. Importantly, the balance of these pathways differs across age groups, with pediatric AD showing stronger Th17/Th22 activity and reduced Th1 signaling compared with adults, and across ethnic populations, with Asian and African American patients displaying distinct Th1/Th17/Th22 patterns relative to European American patients. Together, these variations underscore that AD encompasses multiple immunologic endotypes, reinforcing the need for therapeutic approaches capable of addressing both type 2 and non–type 2 inflammatory pathways across diverse patient populations.^1,19

Mechanisms that perpetuate the cycle of AD

AD disease severity and symptoms can be attributed to underlying mechanisms that prolong the cycle of relapsing episodes. In atopic dermatitis, epidermal barrier dysfunction—from defects in structural proteins, lipids, tight junctions, and enzyme activity—allows penetration of external antigens, triggering keratinocytes to release IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) that activate Langerhans cells, dendritic cells, and ILC2s. This drives a Th2-skewed response with Th2-derived IL-4 and IL-13, which further weaken the barrier and promote the shift from acute Th2/Th22/Th17 activity toward chronic Th2 and Th22 signaling with parallel Th1 involvement. Th2-induced IL-31 fuels the itch–scratch cycle, where scratching trauma amplifies inflammation. Activated memory T cells persist as long-lived populations capable of rapid recall upon antigen reencounter, contributing to disease recurrence and chronicity. Together, these processes create a self-perpetuating barrier–immune feedback loop in which barrier impairment enables immune activation, and immune-derived cytokines further damage the barrier.^1,6,19

T cells are at the center of AD inflammation

T cells orchestrate and amplify inflammatory responses in AD. Multiple T-cell subsets contribute to AD severity, specifically Th2 and Th22 for the acute phase and Th17/Th22/Th1 for chronic/lichenified lesions. Costimulatory signaling, including the OX40L/OX40R interaction, supports T-cell survival, expansion, and cytokine production, reinforcing chronic immune activation.^1,6

Treatment strategies 

Atopic dermatitis (AD) requires a personalized approach for patients
According to American Academy of Dermatology (AAD) and Global Atopic Dermatitis Atlas (GADA) recommendations, treatment usually begins with emollients to strengthen and protect the skin barrier and behavioral modification to avoid triggers. For more moderate-to-severe cases, systemic treatments play a key role in providing relief. A range of options from foundational care to advanced targeted therapies enables personalized management.^11,13,20

Determine the appropriate treatment for patients

When deciding on an appropriate treatment, consider the following^1,13,21,22:
Treatment goals can include controlling symptoms, reducing flares, restoring barrier function, improving quality of life, and achieving long-term disease modification.

Stepped-care approach—matches treatment intensity to disease severity. Treatment approach may escalate or de-escalate based on GADA treatment recommendations.

Guideline-directed care—AAD and international guidelines recommend individualized, stepwise management with shared decision-making.

Chronic disease management—AD requires an ongoing, proactive approach to therapy and maintenance treatment to address persistent inflammation, not just reactive treatment of flares.

In summary, AAD, GADA, and international guidelines emphasize setting clear treatment goals, monitoring progress regularly, addressing subclinical inflammation, and integrating both pharmacologic and supportive care. Selection factors include disease severity and extent, and patient factors such as age, comorbidities, preferences, previous treatment response, and impact on quality of life.

AAD and GADA‑recommended strategies for topical and behavioral management

Nonpharmacological approaches: essentials for patients^13,20

   Emollients, moisturizers, trigger avoidance, gentle skincare

   Barrier restoration and maintenance foundational to all AD management

   Patient education on identifying and avoiding triggers (irritants, allergens, stress) 

Pharmacological approaches

First-line for mild-to-moderate disease: used for care management and maintenance therapy^6,13,20 
   Topical corticosteroids (TCS): Mainstay for acute flare treatment; various potencies available

   Topical calcineurin inhibitors (TCI): Steroid-sparing option, particularly for sensitive areas (face, 
eyelids, genitals)

   Topical phosphodiesterase-4 (PDE4) inhibitors: Anti-inflammatory, steroid-sparing option

   Adjunctive topical approaches: Wet wrap therapy for severe flares; antimicrobials when secondary 
infection present

Advanced topical therapies: advanced topicals expand treatment options for patients with need

Alternatives to traditional topical therapies^13,23
   Topical Janus kinase (JAK) inhibitors: Newer class targeting Janus kinase pathways; provide steroid-sparing anti-inflammatory option for localized disease; approved for mild-to-moderate AD
in patients 2 years of age and older

   Aryl hydrocarbon receptor (AhR) agonists: A steroid-free option that modulates immune response and 
barrier function

Systemic treatment options for moderate-to-severe AD 
When to consider systemic therapy: Systemic therapy should be considered for patients with AD who experience an inadequate response with optimized topical treatments, extensive disease, or significant impact on quality of life. Additionally, with disease requiring frequent or prolonged use of high-potency topical corticosteroids.^1,13

Understanding targeted therapies: Understanding cytokines in AD has enabled targeted biologics and systemic therapies that address underlying immune dysregulation. These therapies represent a major advance in managing moderate-to-severe AD.⁶ 

Biologic therapies aim to directly address immune dysregulation 
Some examples include IL-4/IL-13 inhibitors, IL-31 inhibitor, and JAK inhibitors. IL-4/IL-13 inhibitors block type 2 inflammation by targeting key cytokines that drive disease and were the first biologic class approved for moderate-to-severe atopic dermatitis. IL-31 targets the pruritus pathway and is designed to address itch, one of the most burdensome symptoms in moderate-to-severe AD. JAK inhibitors may provide relief quickly to some moderate-to-severe AD patients. Moreover, broad‑spectrum approaches targeting the Janus kinase pathway can block signaling from multiple cytokines simultaneously, including type 2 and other inflammatory pathways.^6,13,19

Emerging systemic therapies include novel biologics in development targeting OX40L and other immune pathways. However, the clinical significance of these mechanisms is under investigation, so no conclusions regarding safety and efficacy should be drawn. Additional JAK inhibitors are also in the pipeline for the treatment of moderate-to-severe AD. The expanding treatment landscape has the potential to offer more personalized options for patients with AD.¹³