Atopic dermatitis, or eczema, is a frustrating disease. It is uncomfortable, oftentimes painful; it can even interrupt the sufferer’s sleep. Because of self-consciousness, fear of exacerbating their symptoms, or both, many patients limit their participation in their favorite activities. To make matters worse, there is no cure for eczema.
It is no surprise that many eczema sufferers are concerned about passing this frustrating condition down to their children or grandchildren. They come to their dermatologists not only to treat their own symptoms but for answers; “Is eczema hereditary?” They want to know.
Genetics and Disease
The completion of the Human Genome Project in 2003 revolutionized genetics research. The sequencing of the human genome has allowed researchers to find genetic links to many different diseases that were not considered heritable disorders before. As a result, there is more interest than ever in how heredity influences common conditions–including eczema
Some diseases are clearly inherited: a child inherits two copies of a faulty gene, and disease occurs. Other diseases are not so easily categorized; they are not passed down directly, but heredity can play a role in their development.
Eczema is one of the latter. Scientists have made exciting strides in pinpointing genetic and epigenetic factors in the development of atopic dermatitis. To understand how genetics influences eczema, you must first have some understanding of what happens during an eczema flare.
The Root Causes of Eczema
Eczema flares are caused by two major factors: an unhealthy skin microbiome and an inability to Inability to regulate and shut down inflammation and re-establish a healed skin barrier.
Your skin is populated by numerous microbial organisms, or microbiota—this community of microbes is called a microbiome, and it includes normal flora bacteria and yeast. Facial pores can also contain a few microscopic arthropods called demodex. These microbiota work together to ensure the skin’s health.
When the skin’s microbiome is out of balance, disease-causing bacteria overpopulate the skin. Skin scrapings taken from people with atopic dermatitis often show low increased yeast and increased Demodex organisms. Cultures often confirm unhealthy amounts of Staph bacteria, and Gram-negative bacteria. During atopic dermatitis flares, the skin is usually overpopulated by Staphylococcus aureus, which especially contributes to inflammation and strong reactions from our immune system.
In response to this imbalance, the body attempts to fend off the disease-causing bacteria by mounting an immune response. It sends different kinds of cells to the affected site, and they coordinate a cascade of effects intended to ward off the invading bacterium. This immune response causes inflammation, which is recognizable by symptoms all-too-familiar to eczema sufferers—redness, oozing, stinging, and itching, to name a few.
People with healthy, well-regulated immune systems can shut down the inflammation once the disease-causing bacteria are in check. In people with eczema, the body is not capable of interrupting the inflammation once it begins. For them, it continues as the chronic disease we recognize.
How are these two factors—an out-of-balance skin biome and unchecked inflammation—affected by the genes?
Genetics and the Microbiome
Your skin is your body’s largest organ, comprising an estimated 15% of your body weight. It is your body’s first defense against pathogens and harmful particles in the environment. It is protected by a barrier called the stratum corneum, which is made up of flat, shingle-like cells. These cover the stratum spinosum portion of the epidermis, made up of brick wall-like skin cells. Together these create the barrier functions of the skin, when they are healed and healthy.
The skin’s barrier function is protected and enhanced by proteins synthesized by the body. One of these proteins, filaggrin, was discovered in 1977. Filaggrin seems to help barrier function in multiple ways. It seems to both increase moisture retention and influences the pH of the stratum corneum.
The synthesis of filaggrin depends upon a precursor protein called profillagrin. A gene called the FLG gene is responsible for the synthesis of profillagrin. In a manner of speaking, the FLG gene gives the body the code for making profilaggrin.
The FLG gene was identified in the 1980s, and its connection to atopic dermatitis was noted even then. The FLG gene’s large, repetitive nature made it difficult for scientists to sequence it, though. This delayed scientists’ ability to identify its precise relationship to atopic dermatitis.
It was partially sequenced in 1992, but it would be another 14 years before researchers had the technology to sequence the gene in full. In 2006, the FLG gene was completely sequenced. For the first time, researchers could identify the mutations that caused inadequate profilaggrin synthesis.
Basically, the mutations they identified did not provide the correct code for synthesizing profilaggrin. These faulty “instructions” lead to inadequate production of profilaggrin, and by extension, filaggrin. Without adequate amounts of this vital protein, the skin’s barrier function is compromised. This makes it harder to maintain the moisture needed to protect against inflammation secondary to dryness and scaling.
The genetic variation that causes inadequate synthesis of profilaggrin and filaggrin can be passed by a parent to their child. In fact, this is the number one risk factor for the development of atopic dermatitis. This inherited mutation, though, is not an inevitable guarantee that a person will experience eczema. Simultaneously, not everyone who develops eczema has inherited the mutation.
Research points to eczema arising from an elaborate interconnection between genetic factors, lifestyle, and environment. The nature of that interconnection is still poorly understood. We do know, though, that those who inherit mutations on their FLG gene are at a higher risk for eczema flares, especially when they are exposed to other risk factors such as age or environmental irritants. Because their skin’s microbiome and barrier are already compromised, these factors can lead to inflammation and an eczema flare can be triggered.
Genetics and Inflammation
A disharmonious microbiome is but one factor in the development of eczema; another key factor is inflammation. Under normal conditions, the processes that produce inflammation allow the body to isolate, kill, and remove intruding pathogens or irritants. Scratching is another trigger for runaway inflammation.
Once the “invader” is repelled, the body recognizes that it no longer needs to attack, and the inflammation stops. This kind of inflammation is called acute inflammation; it flares up when a pathogen, irritant, or foreign body invades, and it stops when the body succeeds in expelling it. Scratching is another trigger for runaway inflammation.
Unfortunately, many people’s bodies cannot switch off inflammation once it starts. For these people, the immune response continues even after the trigger is isolated or eliminated. This is called chronic inflammation. A person with eczema cannot switch off the body’s response to an unbalanced microbiome or a diminished skin barrier. The inflammation and all the symptoms that come with it continue unabated until they are interrupted by treatment.
Several different genes are involved in regulating the body’s immune response and shutting down inflammation. A mutation in any of these genes can predispose a person to chronic inflammation; like the genetic variations regulating the skin’s protective proteins, these mutations can be passed from parent to child.
For years, doctors noted that people suffering from atopic dermatitis tended to have asthma or an asthmatic family member. The link between these two conditions is now well-established. More recent research has found a correlation between atopic dermatitis, celiac disease, and alopecia areata. Each of these conditions is caused by overactive immune systems, and each correlates to mutations on genes responsible for immune system regulation.
Once again, inheriting genetic mutations associated with inflammatory diseases does not guarantee the development of those diseases. It simply means that people who inherit them are at increased risk. Exposure to other risk factors can trigger inflammatory diseases in this population.
The question of heredity is complicated in the case of eczema. A person who inherits a predisposition to inflammation or compromised barrier function might never develop atopic dermatitis. At the same time, spontaneous mutations of genes responsible for filaggrin production or immune system regulation can occur in people with no prior family history of atopic dermatitis, asthma, or any other inflammatory disease. These mutations can occur during fetal development, and as of now, no definitive causes for them have been identified.
Can Atopic Dermatitis Be Inherited
To shorten and simplify a long, complex story, eczema cannot be inherited—exactly. Mutations on the genes that regulate filaggrin production or the immune system can be. People who inherit these mutations have an increased risk for atopic dermatitis. Spontaneous mutations on these genes can occur in a person with no family history of inflammatory disease, and they can then experience eczema flares. For many, eczema seems to have no genetic cause at all.
Like many conditions, eczema is usually caused by an interplay between heredity and the environment. At this point in human history, people cannot edit out the genetic mutations that predispose them to eczema. However, there are practices that can help protect the skin’s microbiome and reduce inflammation. This includes reducing exposure to common triggers such as mold and pet dander and avoiding excessive sun exposure. In addition, using skin care products such as CeraVe®, Aveeno®, or Cetaphil® moisturizer can help promote healthy barrier function and reduce inflammation. Staying well-hydrated is also important.
Parents worried that their children could develop eczema can use these best practices for maintaining both optimal barrier function and microbiome balance for their children.
Finally, although eczema is incurable, it is treatable. The goal is completely healed healthy skin. When flares occur, using SmartLotion® as illustrated by Dr. Harlan’s protocols can help restore the skin’s microbiome, shut down inflammation, and heal the skin barrier functions. The prebiotic effects in SmartLotion act to help restore conditions in which helpful microorganisms can thrive, while 0.75% hydrocortisone acts to reduce inflammation and fix TSW (topical steroid withdrawal). It’s designed for the most sensitive skin areas, and for all skin types. Combined with proper moisturizing, this strategy has brought relief and contributed to healing for 95% of the patients Dr. Harlan has treated for eczema. SmartLotion should be used according to instructions appropriate for age, and Dr. Harlan recommends that patients use SmartLotion under a physician’s care.