Atopic Dermatitis: 5 Things to Know

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin condition that typically affects the face (cheeks), neck, arms, and legs but usually spares the groin and axillary regions. AD usually starts in early infancy but also affects some adults. AD is often associated with elevated levels of immunoglobulin E (IgE). That it is the first disease to present in a series of allergic diseases — including food allergy, asthma, and allergic rhinitis, in order — has given rise to the "atopic march" theory, which suggests that AD is part of a progression that may lead to subsequent allergic disease at other epithelial barrier surfaces.

Here are 5 things to know about atopic dermatitis.

1. Essential features of AD are pruritus and eczema.

The diagnosis of AD is primarily observational. It is made on the basis of patient and family history, pattern of lesions, morphology, and clinical signs. No genetic features or biomarkers are specific enough to reliably aid in diagnosis or severity assessment. Many individual findings are used to diagnose AD, as summarized by the American Academy of Dermatology (AAD) based on essential, important, associated, and exclusionary features:

Essential features (must be present for diagnosis) are (1) pruritus and (2) eczema (acute, subacute, or chronic) with typical morphology and age-specific patterns and chronic or relapsing history.
Important features (usually seen in AD and support the diagnosis) are (1) early age of onset, (2) atopy (personal/family history, IgE reactivity), and (3) xerosis.
Associated features (nonspecific but suggestive) are (1) atypical vascular response (eg, delayed blanch response); (2) keratosis pilaris (and some others); (3) ocular/periorbital changes; (4) other regional findings (eg, perioral changes); (5) and perifollicular accentuation, lichenification, or prurigo lesions.
Exclusionary conditions (must be excluded to make the AD diagnosis) are (1) scabies, (2) seborrheic dermatitis, (3) contact dermatitis, (4) ichthyoses, (5) cutaneous T-cell lymphoma, (6) psoriasis, (7) photosensitivity dermatoses, (8) immune deficiency diseases, and (9) erythroderma due to other causes.

AD should be differentiated from other red, scaly skin conditions. It is often difficult to separate AD from seborrheic dermatitis in infancy, and the two conditions may overlap in this age group. Particularly if the condition is not responding to therapy, the diagnosis of AD should be re-reviewed and other disorders considered, including more serious nutritional, metabolic, and immunologic conditions in children and cutaneous T-cell lymphoma in adults. Allergic contact dermatitis may be both an alternative diagnosis to AD and an exacerbator of AD in some individuals.

2. Associated comorbidities of AD may exacerbate the condition and lead to other atopic disorders.

Reported comorbidities of AD include other atopic or allergic conditions, autoimmune diseases, infections, metabolic conditions, mental health disorders, and cardiovascular disease. Certain aspects of AD, such as chronic pruritus, psychosocial distress, and inflammation, can lead to anxiety, depression, and suicidality. AD is associated with and may predispose to higher risk for other atopic disorders, including asthma, hay fever, food allergy, and eosinophilic esophagitis.

Persons with AD also appear to be at higher risk for infectious diseases. The prevalence of cutaneous and systemic infections in patients with AD is significantly higher than those without AD. Infectious complications can include skin and soft-tissue infections, bacteremia, eczema herpeticum, osteomyelitis, endocarditis, and septic arthritis.

3. Climate change has a profound impact on AD.

The incidence of AD has increased over the past several decades, and environmental factors such as climate change have been implicated as a potential mechanism. Climate change–related factors affect the skin's capacity to maintain homeostasis, leading to various cutaneous diseases. AD, psoriasis, pemphigus, acne vulgaris, melasma, and photoaging are all associated with rising levels of air pollution. Elevated temperatures due to global warming induce disruption of the skin microbiome, thereby affecting AD.

Extreme weather events due to climate change, including floods and wildfires, are implicated in cutaneous injuries, skin infections, and acute worsening of inflammatory skin disorders.

4. The impact and appearance of AD varies in different racial groups.

It was once believed that AD was just one single disease affecting people of many different races. More recently, it has been proposed that AD is in fact a group of different diseases. Both epidemiologic and genetic factors may play a role in influencing the main features of AD.

Spongiotic processes such as AD that would be pink or erythematous on white skin are often hypopigmented in individuals with darkly pigmented skin. AD has a higher prevalence and severity in Black and mixed-race populations, probably owing to a combination of environmental and intrinsic factors. Black skin has been shown to have increased transepidermal water loss and lower levels of ceramides, which are important components of the lipid barrier in the stratum corneum.

The American College of Allergy, Asthma & Immunology, along with the Allergy & Asthma Network, are partnering to create Eczema in Skin of Color, a website to aid physicians and patients in recognizing eczema in people with all skin types.

5. New and emerging therapies are poised to improve outcomes with AD treatment.

Ruxolitinib cream, a topical Janus kinase (JAK)–1/JAK2 inhibitor, was approved for AD by the US Food and Drug Administration (FDA) in September 2021. The approval was based on results from the Topical Ruxolitinib Evaluation in AD (TRuE-AD) clinical trial program, which consisted of phase 3 studies that investigated 1249 patients aged ≥ 12 years with mild to moderate AD (Investigator's Global Assessment score of 2-3) with a body surface area of 3%-20% (excluding scalp). The 2023 AAD guidelines for topical treatment recommend ruxolitinib cream for adults with mild to moderate AD.

Tralokinumab is a monoclonal antibody that inhibits the interleukin-13 cytokines, which prevents the release of cytokines, chemokines, and IgE. It was approved by the FDA in 2021 for treatment of moderate to severe AD. It is administered by subcutaneous injection every 2 weeks. Approval was based on the phase 3 trials ECZTRA 1, 2, and 3, which assessed the efficacy of tralokinumab in 1934 adults.

Abrocitinib is an oral, once-daily JAK1 inhibitor for treatment of adults living with refractory, moderate to severe AD. FDA approval was based on results of five clinical trials from a large-scale trial program of more than 1600 patients. Across the trials, abrocitinib demonstrated a consistent safety profile and profound improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after 2 weeks, for some people living with AD vs placebo.

Upadacitinib, another oral JAK1 inhibitor, was approved by the FDA in January 2022 for refractory moderate to severe AD. Approval was based on three double-blind phase 3 trials (Measure Up 1, Measure Up 2, AD Up) in which 2584 patients with moderate to severe AD were randomized to receive oral upadacitinib 15 mg/d and 30 mg/d. In Measure Up 1 and Measure Up 2, upadacitinib was evaluated as monotherapy; in AD Up, upadacitinib was evaluated in combination with topical corticosteroids.

On the Horizon

Baricitinib, an oral JAK1/2 inhibitor, is not yet approved by the FDA for AD. It is, however, approved for moderate to severe AD treatment in the European Union and many other countries. A 2022 review of studies evaluating baricitinib for the treatment of moderate to severe AD in adults (BREEZE-AD1, -AD2, -AD3, -AD4, -AD5, -AD6) reported that current evidence supports baricitinib, used as monotherapy or in combination with topical corticosteroids, as a safe and effective agent that can be used as an alternative to subcutaneous biologics in adults with moderate to severe AD.

Topical JAK Inhibitors

A 2023 systematic review (19 studies, 3600 participants) reported on several topical JAK inhibitors that are effective for treating AD. It suggests a stronger safety profile and better results compared with systemic JAK inhibitors. The review focused on topical delgocitinib, tofacitinib, ruxolitinib, cerdulatinib, and ifidancitinib. All agents were effective in treating AD. All of these topical JAK inhibitors had minimal risk for mild to moderate adverse effects.

Biologics

Lebrikizumab was evaluated in a phase 2b, double-blind, placebo-controlled randomized clinical trial. After 16 weeks (280 participants), patients with moderate to severe AD showed a dose-dependent significant improvement in the primary endpoint compared with placebo. Two phase 3 trials (ADvocate1, ADvocate2) evaluated the safety and efficacy of monotherapy with lebrikizumab in adults and adolescents with moderate to severe AD.

Nemolizumab, assessed in long-term phase 3 trials of AD-associated pruritus, resulted in clinically meaningful improvements from the beginning of treatment to week 68. Nemolizumab is being evaluated in two identical phase 3 studies (Arcadia 1, Arcadia 2) and a long-term extension study.

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