Eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition characterized by itchy, red, swollen, and cracked skin. Globally, eczema affects approximately 10% to 20% of children and 2% to 10% of adults, impacting about 31.6 million people in the United States. Research aims to understand its biological underpinnings, including genetic predispositions, immune system dysregulation, skin barrier dysfunction, and the skin microbiome.
Deciphering Eczema’s Underlying Mechanisms
Research focuses on understanding the biological processes contributing to eczema’s development. Genetic predispositions, particularly mutations in the filaggrin gene (FLG), are a significant area of study. Filaggrin, a protein maintaining skin hydration and barrier function, can lead to increased skin permeability and dry skin when deficient, a hallmark of eczema. Mutations in this gene are found in an estimated 30% to 50% of white eczema patients and are associated with a higher risk of early disease onset, elevated IgE levels, and persistence into adulthood.
Immune system dysregulation is another area of investigation, focusing on Type 2 inflammation. This immune response is driven by activated T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s), producing cytokines like interleukin (IL)-4, IL-5, IL-13, and IL-31. These cytokines contribute to the inflammation, itching, and skin barrier disruption seen in eczema. Understanding these immune pathways informs the development of targeted therapies.
The skin barrier’s integrity is closely linked to the immune response and genetic factors. When impaired, it allows allergens and irritants to penetrate more easily, triggering immune responses and inflammation. Even without filaggrin gene mutations, decreased filaggrin levels suggest a broader role for skin barrier disruption in eczema development.
The skin microbiome, microorganisms on the skin, also plays a role in eczema. Staphylococcus aureus colonization is common on the skin of individuals with eczema, with higher rates in lesional skin compared to non-lesional skin. Around 80% of people with eczema have S. aureus on their skin, compared to about 10% of the general population. This bacterium produces toxins, like delta toxin, which triggers immune cells to release inflammatory granules, contributing to eczema-like rashes.
Developing Novel Therapies
Understanding eczema’s underlying mechanisms has led to the development of novel targeted therapies. Monoclonal antibodies, a class of biologics, block specific inflammatory pathways. Dupilumab, for instance, targets the IL-4Rα subunit, inhibiting IL-4 and IL-13 signaling, central to Type 2 inflammation. Tralokinumab and lebrikizumab are other monoclonal antibodies that specifically inhibit IL-13, preventing receptor binding and reducing inflammatory effects. These biologics aim to address the root causes of inflammation rather than just managing symptoms.
Another promising class of treatments is Janus kinase (JAK) inhibitors, which modulate intracellular signaling pathways. JAK enzymes drive abnormal immune responses by transmitting signals from inflammatory cytokines. Blocking these pathways, JAK inhibitors reduce inflammation and itching associated with eczema. Several JAK inhibitors, such as abrocitinib, upadacitinib, and ruxolitinib, have been approved or are under investigation for eczema, with both oral and topical formulations showing rapid reductions in itch and improvements in skin clearance.
Beyond biologics and JAK inhibitors, research is exploring new topical non-steroidal options. These treatments provide effective symptom relief without side effects associated with prolonged topical corticosteroid use, such as skin thinning. Examples include topical phosphodiesterase-4 (PDE-4) inhibitors like roflumilast and aryl hydrocarbon receptor agonists like tapinarof, which work through different mechanisms to reduce inflammation and itching. These newer topical agents represent an expanding array of choices for managing mild to moderate eczema.
Innovations in Diagnosis and Personalized Medicine
Research focuses on refining eczema diagnosis and tailoring treatments to individual patient profiles. Identifying biomarkers is a significant innovation. These measurable biological indicators provide insights into disease severity, predict treatment response, or categorize specific eczema subtypes. Biomarkers can be found in blood samples or skin biopsies.
High baseline levels of serum dipeptidyl peptidase-4 (DPP-4) and periostin, indicating increased IL-13 activity, have been identified as biomarkers for a favorable response to tralokinumab, an IL-13 blocking antibody. Baseline IL-22 expression in skin biopsies correlates with improved clinical and transcriptomic responses to fezakinumab, an anti-IL-22 treatment. While total IgE levels are often elevated in eczema, their correlation with treatment response to specific therapies like dupilumab is not always clear, though changes in IgE levels during treatment may serve as a monitoring tool.
Personalized medicine in eczema aims to match treatments to patients based on their unique biological characteristics. Researchers classify eczema patients into distinct “endotypes” based on molecular profiles, such as dominant immune pathways or skin barrier characteristics. This approach moves beyond a “one-size-fits-all” model, optimizing therapeutic outcomes by selecting treatments that specifically address a patient’s underlying biological drivers of the disease.
Exploring Environmental and Lifestyle Influences
Research continues to investigate the impact of external factors and lifestyle choices on eczema development and flare-ups. Environmental allergens and irritants are well-known triggers. Studies examine how exposure to substances like dust mites, certain fabrics, harsh soaps, and skincare products can exacerbate eczema symptoms. This research identifies specific triggers, enabling more effective avoidance strategies.
The role of pollution is also under scrutiny. Studies suggest that increased exposure to fine particulate matter (PM2.5) in the air may increase eczema risk. For example, for every increase of 10 µm/m³ in average PM2.5 air pollution, individuals were more than twice as likely to have eczema. Climate factors, including temperature and humidity, also influence skin health. Low humidity can lead to dry, itchy skin, while high humidity causes sweating that can worsen pruritus.
The influence of diet and the gut microbiome on skin health, often referred to as the “gut-skin axis,” is an expanding area of research. Studies suggest a link between an imbalanced gut microbiome, with reduced beneficial bacteria and increased harmful ones, and eczema symptoms. Some studies indicate that a diet rich in fruits and fermented foods may lower eczema risk, and certain probiotic strains like Lactobacillus and Bifidobacterium may offer a protective effect, particularly in infants.