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A growing body of evidence suggests that atopic dermatitis (AD) goes more than skin deep, often traveling with a host of physical and mental comorbidities and exacting a dramatic toll on the quality of life of affected families. Here, Vivian Y. Shi, MD, an associate professor in the department of dermatology at the University of Arkansas for Medical Sciences in Little Rock, discusses the changing paradigm and what it may mean for atopic dermatitis patients today and in the future.

What do we know about the relationship between the skin microbiome and atopic dermatitis?

Vivian Y. Shi, MD: They are intimately associated. The skin of people with AD is commonly colonized by Staphylococcus aureus (SA). SA secreted toxins, enzymes, and cell-surface-associated antigens worsen the skin barrier and cause skin inflammation. The skin of AD patients also has diminished antimicrobial peptides with disrupted innate immune defense, which makes their skin more prone to infections. In fact, research from the National Institutes of Health has shown a close temporal association between AD flares and microbiome changes on the skin. During a flare, there is an increase in SA load and decrease in microbial diversity; the opposite happens when the skin improves with treatment.

What are some of the most exciting areas of research in AD?

Dr. Shi: Our understanding of the etiologies of AD is expanding along with the availability of new targeted medications. One area that is particularly exciting is neuro-immune-skin crosstalk, where the dysregulation of the neuroimmune circuit is closely linked to skin barrier defect, inflammation, and itch. Novel targeted therapies, such as anti-interleukin (IL) 4/13 biologics and Janus kinase (JAK) inhibitors (both topical and oral) help to control the dysregulated circuit to optimize control of all the pathoetiologies known to cause AD.

How does AD affect quality of life/family dynamics?

Dr. Shi: AD can profoundly affect the quality of life of a patient and family dynamics. There is research showing that AD has similar impact as other chronic childhood disorders and is only second to cerebral palsy. Other studies have shown that raising a child with AD can have a more negative impact on the family than raising a child with type I diabetes. AD and sleep disruption can negatively affect school and work performance and cause anxiety and depression in the patient and their family.

What do we know about AD comorbidities?

Dr. Shi: There are many physical and psychological comorbidities associated with AD. The strongest evidence is on the atopic triad, which includes AD, asthma, and allergic rhinitis. Other atopic conditions with high associations are food allergies, eosinophilic esophagitis, urticaria, and allergic conjunctivitis. Other comorbidities have a less clear link with AD, but more real-world data is showing some association. These include cardiovascular diseases, metabolic syndrome, and malignancies. The psychological comorbidities with the strongest associations tend to be anxiety, depression, and fatigue. In children with AD, there can be behavioral issues such as conversion/somatoform disorders and developmental/intellectual disabilities, attention-deficit/hyperactivity, disorders (ADHD) and obsessive-compulsive disorder(OCD).

Will treating AD aggressively prevent the Atopic March?

Dr. Shi: Possibly. The term “atopic march” describes a sequential development progression of atopic diseases from AD to asthma to allergic rhinitis. However not all patients with AD will go through the march, and many do not develop all components of the march. Early evidence came from mouse models where allergen entry through a defective skin barrier can lead to systemic allergen sensitization, but we need more vigorous epidemiologic and mechanistic evidence. Nevertheless, aggressive treatment of AD should be done to alleviate the disease burden, and if it does prevent the atopic march, that’s the icing on the cake!

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