Atopic Dermatitis: A Personalized Approach May Improve Outcomes

A recent review published in the Journal of Personalized Medicine presents evidence of a high risk of developing systemic inflammation, particularly in the case of persistent and severe atopic dermatitis (AD). Thus early treatment of the disease using precision medicine is crucial to control and modify the course of the condition and associated comorbidities.

AD is a disorder that can easily be summarized by a single word: "heterogeneity" since all aspects of the disease, including its name, treatment strategies, and clinical course, show some level of heterogeneity. This heterogeneity reflects multiple pathogenetic mechanisms, causing varying degrees of epidermal barrier disruption, T cell subsets activation and microbial dysbiosis. Such diverse features raise the question of whether AD is a single disease or a set of diseases with a shared phenotype. Jeffrey Weinberg, MD, clinical professor of dermatology at Mount Sinai School of Medicine in New York, says regarding AD, "Current evidence is beginning to demonstrate that there is heterogeneity of phenotypes involved. These characteristics include age at onset, triggers, comorbidities, physiological traits, ethnic background, inflammation types, and treatment responses."

Due to its diverse clinical representations, defining and diagnosing AD can be challenging. However, AD can be defined as a prevalent chronic, pruritic, inflammatory skin condition characterized by dry, painful, and itchy rashes. According to the American Academy of Dermatology Association, about 1 in every 10 Americans lives with the disease, which not only affects patients' quality of life but also poses a significant burden on healthcare resources. AD may be considered a starting point of an atopic march in many patients, comprising allergic diseases, such as allergic rhinitis, asthma, and food allergy. According to research, about 25% of people with atopic dermatitis develop asthma, and the risk increases with the disease severity^1.

Although AD has complex and multifactorial pathophysiology, epidermal barrier dysfunction and type 2 inflammation are the most potent factors associated with AD lesions. Epidermal barrier dysfunction can either be attributed to genetic mutations responsible for causing long-lasting and early-onset AD or an underlying inflammatory reaction due to innate or adaptive immune responses. In contrast, barrier-damaging agents like pollution, stress, and diet may well explain the increase in AD cases.

Evidence suggests that epidermal barrier dysfunction and activation of an innate immune response due to genetic mutations, allergens, and modified microbes induce T2 inflammation, which may eventually lead to the atopic march². Since damaged keratinocytes release certain cytokines, uric acid, HMGB1and S100 proteins, creating a pro-T2 inflammatory environment and inducing serum IgE levels.

The magnitude of the barrier dysfunction directly correlates with the severity of the disease. Any disruption to the skin barrier allows the irritants to cause inflammation by getting deeper into the skin and makes it difficult for the skin to retain moisture, leading to itchy and dry skin.

Since a systemic factor is involved here, the review recommends an early treatment in a tailored approach for the disease.

Previously the management of AD was based on avoiding and managing triggers, emollient therapy, and antimicrobial and anti-inflammatory therapy, depending on the severity of each case. New strategies have now shifted the focus from symptom control to disease modification by using endotype-driven biologics.

Although there are multiple treatment strategies for AD, due to the heterogeneous nature of patients' responses to the treatment, there is no one-size-fits-all treatment for the disease.

The review recommends using precision medicine to treat patients suffering from AD. Precision medicine, also known as personalized medicine, is an emerging technique that prevents adverse events, improves clinical outcomes, and predicts effective treatment options for patients, considering the variability in their environment, genes, and lifestyles.

Identifying factors predisposing a person to a particular condition and underlying causative mechanisms can help tailor personalized preventive and treatment strategies for each patient.

Regarding precision medicine, Weinberg explains, "Moving from clinical to molecular approaches to define endotypes could now lead to more targeted and personalized approaches to AD therapy. Newer strategies are looking at potentially modifying disease using biologics to target individual inflammatory pathways."

"Awareness of the pathways involved in different patients can lead to a more personalized approach of treating the disease," he further suggests.

Many researchers see this approach as a game-changer, but change does not come that easily. Our healthcare system is more focused on treating the sick rather than keeping people healthier. To make this approach a success, we need to change the mindset of the people so that they can invest in their health before contracting a disease.

When asked about the limitations of the review, Weinberg shows speculations regarding the validity of the approach and says, "we are yet to see results from real-world treatment in order to confirm the validity of the approach."

References:

1. Ravnborg N, Ambikaibalan D, Agnihotri G, et al. Prevalence of asthma in patients with atopic dermatitis: A systematic review and meta-analysis. J Am Acad Dermatol. 2021;84(2):471-478. doi:10.1016/j.jaad.2020.02.055
2. Hill DA, Spergel JM. The atopic march: Critical evidence and clinical relevance [published correction appears in Ann Allergy Asthma Immunol.] Ann Allergy Asthma Immunol. 2018;120(2):131-137. doi:10.1016/j.anai.2017.10.037