Is Atopic Dermatitis a Systemic Condition?

Atopic dermatitis (AD) affects the skin, and while several patches of skin might be affected in an individual, AD has typically been considered a localized disease, as the skin is just one part of the body. However, researchers are connecting the dots between AD and comorbidities – conditions that occur at the same time in a patient – and proposing that AD might actually be a systemic disease (one that affects the entire body).

The atopic march

AD most often begins in infancy or childhood, although it occasionally can begin in adulthood. Many children who first develop AD also experience additional allergic diseases like food allergies, asthma, and hay fever (also known as allergic rhinitis). This progression has been termed the “atopic march.” However, researchers believe that the atopic march may not be as sequential as first believed. The various allergic diseases may occur at the same time or may happen in a different order in various individuals. Researchers also point out that many people with AD frequently experience hand eczema and allergic contact dermatitis in adulthood, although these conditions haven’t been previously included as members of the atopic march.¹

Immune system dysfunction

While the exact mechanisms of how AD develops aren’t fully understood, experts know a combination of factors contributes to the development of the disease, including a dysfunction in the immune system, a dysfunction in the barrier of the skin, genetic mutations, and environmental elements. Researchers have uncovered some of the immune system abnormalities, such as the cytokines (chemical messengers) released by T helper cells 2 (Th2) and Th22. T helper cells work by releasing cytokines to rally other immune cells and increase inflammation in the area. The cytokines from Th2 and Th22 are found in increased numbers in people with AD, and researchers have found that, in addition to increasing inflammation, these cytokines suppress the production of the protein filaggrin, a protein that is essential to creating a healthy barrier in the skin.¹

The immune system abnormalities in people with AD aren’t just local to the affected skin – several of the immune system characteristics of AD can be seen in the blood throughout the body. In addition to the increased cytokines of Th2 and Th22, 80% of people with AD have elevated levels of immunoglobulin E (IgE), which is associated with allergies. The blood from people with AD also contains a unique B cell signature. (B cells are the white blood cells that make antibodies against specific bacteria, viruses, or toxins.)¹

Commonalities with other conditions

Researchers have found several genetic mutations that are associated with an increased risk of certain diseases. Some of these susceptibility mutations have been found to be common between AD and other diseases that involve an immune system dysfunction, such as psoriasis, inflammatory bowel disease, and alopecia areata. Several clinical trials have also found people with AD have a slightly increased risk of developing rheumatoid arthritis, inflammatory bowel disease, and lupus erythematosus.¹

In addition to immune-related conditions, studies have documented that there is an association between AD, obesity, and cardiovascular (heart) disease. Both children and adults with AD have higher rates of being overweight or obese than people without AD. Moderate to severe AD in children is also associated with a higher rate of increased blood pressure, and adults with AD have higher odds of high blood pressure, adult-onset diabetes, and high cholesterol – all conditions that increase heart disease.¹

Psychological diseases are also found at a higher rate among people with AD, including depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and autism. While the underlying mechanisms between psychological conditions and AD aren’t clear, the burden of living with AD, including the unbearable chronic itch and impact on sleep quality, may contribute. Immune system dysfunctions may also play a role in the higher rates of psychological diseases in people with AD.¹

Why is this important?

More studies are needed to understand the biological mechanisms that connect all these conditions, but these findings also lead researchers to consider AD as a systemic condition. The categorization of AD as a systemic condition may also influence treatment and research into better interventions.¹