Is Eczema Genetic, Environmental, or Both?

Eczema, or atopic dermatitis, is a chronic condition causing dry, itchy, and inflamed skin that affects millions worldwide. Its complex origins raise questions about the influence of inherited traits versus external surroundings. The development of eczema involves a combination of genetic predispositions and environmental factors, with ongoing research exploring the distinct roles that nature and nurture play.

Understanding Genetic Susceptibility to Eczema

Evidence for a strong genetic component in the development of atopic dermatitis is well-established through familial and population studies. The condition frequently runs in families, and children with one parent who has eczema, asthma, or hay fever have a significantly increased risk. This risk becomes more pronounced when both parents are affected. The hereditary nature is further illuminated by twin studies comparing identical and fraternal twins.

Concordance rates for atopic dermatitis in identical twins, who share nearly all their DNA, range from 0.72 to 0.86. In contrast, fraternal twins, who share about half their DNA, have much lower rates of 0.15 to 0.23. This difference suggests that genetic factors account for a large portion of susceptibility, with heritability estimated to be around 75%. However, since concordance in identical twins is not 100%, genetics are not the sole determinant.

Research has identified several genes associated with eczema, but mutations in the filaggrin (FLG) gene are the most significant known risk factor. Filaggrin is a protein that helps form the protective outer layer of the skin. Loss-of-function mutations in the FLG gene impair this barrier, and up to 50% of people with moderate to severe eczema may carry such a mutation.

Key Environmental Factors in Eczema Flare-Ups

While a person’s genetic makeup can create a predisposition for eczema, environmental factors often act as the direct triggers for flare-ups. These external influences are diverse and can provoke skin inflammation and worsen symptoms.

Common environmental triggers include:

• Irritants: Substances that directly cause skin inflammation upon contact. Common examples include soaps, detergents, and disinfectants, which strip the skin of its natural oils and compromise its protective barrier. Certain fabrics, like wool and some synthetic fibers, can also mechanically irritate sensitive skin.
• Allergens: Substances that provoke an immune system reaction, leading to inflammation. These include airborne particles like dust mites, pollens, and pet dander, as well as certain foods. The delay between exposure and a skin reaction can sometimes make it difficult to identify the specific trigger.
• Climatic Changes: Low humidity and cold, dry air can increase skin dryness, while hot, humid conditions can cause sweating that irritates the skin. Sudden temperature shifts are also a common trigger.
• Skin Infections: Bacteria, such as Staphylococcus aureus, as well as certain viruses or fungi, can trigger or worsen eczema.
• Emotional Stress: High levels of stress can prompt the body to release hormones that drive inflammation, leading to the onset or intensification of a flare-up.

Gene-Environment Interaction in Eczema

The development of eczema rarely stems from genetics or the environment acting in isolation; it arises from a complex interplay between the two. Having a genetic predisposition does not guarantee that a person will develop atopic dermatitis. Environmental factors often act on an underlying genetic vulnerability to initiate the disease process, which explains why some people with genetic risk factors develop eczema while others do not.

The relationship involving the filaggrin (FLG) gene provides a clear example. An individual with an FLG mutation has a compromised skin barrier, making them more susceptible to environmental triggers. When a person with this mutation is exposed to harsh soaps or dry air, their skin is less able to withstand the damage compared to someone with a fully functional filaggrin protein.

Specific studies have provided direct evidence of these interactions. Research has shown that neonatal exposure to cats increases the risk of eczema in infants who carry an FLG loss-of-function mutation. The combination of the mutation and early-life cat ownership elevated the risk substantially more than either factor alone. Other factors like water hardness have been shown to have a greater impact on individuals with these mutations.

This interplay means the expression of eczema can vary widely among individuals, even within the same family. A person with a genetic predisposition might experience severe eczema due to environmental exposures, while a relative with the same genetic makeup might have only mild symptoms in a different environment.

The Role of Skin Barrier and Immune Response

The symptoms of eczema result from two interconnected processes: a dysfunctional skin barrier and an altered immune response. Genetically, mutations in the FLG gene can lead to an insufficient supply of the filaggrin protein, which is needed to form a strong outer skin layer. This deficiency results in a “leaky” barrier with gaps between skin cells, allowing moisture to escape and irritants to enter.

Environmental factors also damage this barrier. Irritants like detergents chemically strip away protective lipids, while allergens can penetrate the weakened barrier. Once compromised, the barrier allows microbes and allergens to pass into the deeper layers of the skin, which alerts the body’s immune system to mount an exaggerated response.

The immune reaction is characterized by Type 2 inflammation, driven by T helper 2 (Th2) cells. These cells release signaling proteins (cytokines) like interleukin-4 (IL-4) and interleukin-13 (IL-13). These cytokines are responsible for the classic symptoms, promoting allergic reactions and causing the intense itching and inflammation of a flare-up.

This process creates a self-perpetuating cycle. The inflammation driven by the immune response can further weaken the skin barrier, as some cytokines suppress filaggrin production. The resulting itch prompts scratching, which physically damages the skin. This damage degrades the barrier further, allowing more irritants to enter and triggering an even stronger immune response, sustaining the chronic nature of eczema.