Is Atopic Dermatitis an Autoimmune Disorder?

Affecting at least 230 million people globally, atopic dermatitis is one of the most common skin diseases. It causes itching, scaling, oozing, and other uncomfortable symptoms, all hallmarks of inflammation caused by a heightened immune response. 

Recent studies have shown that a large number of people with autoimmune diseases, among them lupus, Crohn’s disease, and rheumatoid arthritis also suffer from atopic dermatitis. This association has spurred numerous conjectures about how atopic dermatitis could be related to the autoimmune disease. Lay people often ask if eczema is, in fact, an autoimmune disorder. 

What role does the immune system play in eczema flares? What is an autoimmune disease, and what is the link between autoimmune diseases and atopic dermatitis? 

To get closer to an understanding of how atopic dermatitis and autoimmune disease might be related, we must first understand a little about the human immune system and its role in eczema flares. 

A Well-Coordinated Defense

 

 

Our immune system exists to protect us from invasion by microorganisms and foreign particles, or antigens. An antigen’s invasion of tissues immediately sets off an elaborate chain of signals and responses between cells. Through these signals and subsequent responses, cells play their designated role in defense against antigens and repair of injured tissues. When their tasks are accomplished, they receive a signal to stand down.  

Cells in the body’s tissues contain pattern recognition receptors (PRR) that are responsible for distinguishing between the body’s own cells and those of pathogens (one example is Langerhans cells, which are localized to your skin–your immune system’s first line of defense). Injured cells activate these PRRs, and the cells release chemicals called inflammatory mediators. These chemicals immediately send out an SOS, recruiting neutrophils, macrophages, and other cells to help them repel the intruder and heal the injured tissues.  

Each cell recruited plays its own role in the immune response. Some act on the blood vessels, dilating them to encourage blood flow to the injured tissues; some work to draw fluids to the tissues to facilitate healing. Others act on mucus membranes to stimulate increased production of mucus.  

Inflammation is the outward result of this well-coordinated response. Injured tissues are repaired through this process, while the offending antigen is ejected. The inflammation resolves once this is accomplished, usually over the course of days. 

The macrophages that gather the remnants of the invading cells “present” the antigen’s molecular information to helper T cells. These cells ferry the molecular code of the antigen, as presented by the macrophages, to the lymph nodes, where they activate T cells. The T cells then signal the B cells that generate antibodies against those specific antigens. 

 

A Blurry Line 

 

 

The T cell’s intervention marks an interesting line between two different parts of the immune system. Inflammation is the work of the innate immune system. It is a defense system present from birth; it includes your skin (your first line of defense), your mucus membranes, and a host of cells such as neutrophils, macrophages, and dendritic cells. The innate immune system is nonspecific; it does not target individual antigens. 

The enhanced response initiated by helper T cells is a function of our adaptive immune system, also known as the “acquired immune system.” We are not born with adaptive immune system pathogens; it develops as we are exposed to antigens. It engineers specific responses to specific antigens and often gives us immunity to any future attacks by those antigens. 

The helper T cells play a key role in the adaptive immune system, so much so that they are often presented as the line between the innate and adaptive immune systems. Many scientists now believe that the T cells communicate with the cells involved in innate immune responses at a much earlier stage than is widely believed. The line between the two systems might not be as distinct as we think. 

 

When the Immune System Misfires

 

 

The outline above is a crude sketch of sophisticated processes. These systems rely on the cells mentioned above (and many others), which trigger the initiation of specific responses as well as their cessation. When it works properly, the immune system recognizes antigens, eliminates them, and then stands down. 

People with conditions like eczema, asthma, or allergy have excitable innate immune systems. The dust mites, mold, and cat dander that most people tolerate without much response trigger intense inflammation for these people. Moreover, once the inflammation begins, be it in the skin, the lungs, or the nasal passages, their immune systems remain on high alert. The inflammatory march continues; chronic inflammation is evidence of this ongoing warfare. Atopic dermatitis is an inflammatory disease of the innate immune system. 

When the adaptive immune system misfires, the cells responsible for targeting specific antigens fail to differentiate between a pathogen and the body’s own cells (or self-tissues). It recognizes certain cells of the patient’s own tissues as an invader, and it sends targeted antibodies or lymphocytes to attack those cells. 

This “friendly fire” might injure multiple systems, as in the case of lupus. Alternatively, lymphocytes might attack only specific tissues, such as the bowels (as in inflammatory bowel disease) or synovial tissues (as with rheumatoid arthritis). The antibodies do not recognize these tissues as their own. Because the body cannot rid itself of its own tissues, it continues to manufacture antibodies against those tissues. This results in damaged self-tissue; the innate immune system responds to the damage with the same inflammatory process it would mount in response to any injury. 

Diseases caused by this cellular infighting are known as autoimmune diseases. It is not certain at this time what causes autoimmune disease. Most autoimmune disorders are not heritable per se, but genetic mutations seem to predispose some people to autoimmune disease. Because many of these diseases have a strong association with certain viruses, such as Epstein-Barr, researchers have postulated that exposure to these viruses might trigger autoimmune disease in people who are predisposed. 

Autoimmune Disease and Eczema

 

 

As you’ve already read, atopic dermatitis is a disease involving the innate immune system, while autoimmune disease involves the adaptive immune system.  How, then, are the two related?  Could eczema be a disease of both the innate immune system and the adaptive?

As we mentioned at the beginning, many studies over the past few years have indicated a strong correlation between atopic dermatitis and several autoimmune diseases. These diseases include lupus, which affects many systems, including the joints and the skin, Crohn’s Disease, which affects the bowels, and Vitiligo. which affects the skin.

Atopic dermatitis seems to be more prevalent among people with two co-occurring autoimmune diseases than it is among those with only one autoimmune disease. Atopic dermatitis often precedes an autoimmune disorder diagnosis; this seems to be especially true for people who develop eczema before adulthood.

It is perhaps unsurprising that atopic dermatitis was found to occur most often alongside autoimmune diseases affecting the skin, such as vitiligo. Interestingly, it was also found to be comorbid with a number of diseases affecting the bowels.

Genome-wide association studies (GWAS) have allowed scientists to wholly examine the DNA of a given group for commonly shared genes and mutations. A GWAS enables researchers to pinpoint susceptibility loci, or heritable mutations that increase risk of a disease. 

A recent GWAS of people with atopic dermatitis identified ten new susceptibility loci for eczema. Each of these susceptibility loci is also associated with adaptive immune system regulation. 

Atopic dermatitis and autoimmune diseases both feature dysregulated immune responses. Dysfunction in helper T cells, which are activated in both innate and adaptive immune responses, is found in both atopic dermatitis and autoimmune disease. 

There is an indisputable relationship between atopic dermatitis and autoimmune disease. The exact nature of that relationship is still not clearly understood. Future studies might allow us to better understand how autoimmune disorders and eczema are connected.  

From the dermatologist's viewpoint, many people with autoimmune disease never experience atopic dermatitis. And people with atopic dermatitis never develop an autoimmune disease. 

What we know now is that the innate immune system and its inflammatory response play the leading role in eczema flares. Addressing that inflammation is critical to both the patient’s comfort and the health of their skin. 

Ninety-five percent of the patients Dr. Harlan has treated for eczema have found relief from inflammation by using a combination of SmartLotionⓇ and proper moisturizing. Its prebiotic properties foster healthy skin flora, while 0.75% hydrocortisone acts to reduce inflammation.

 

- Zula Elwood