Is Eczema an Autoimmune Disease?

What is Eczema?

Healthy skin aids in moisture retention and protects against germs, irritants, and allergies. This allows environmental factors and allergens to harm your skin. Eczema (atopic dermatitis) is caused by a genetic mutation that impairs the skin's capacity to offer this protection, describing a series of disorders that can create itchy, inflamed, and red skin in lighter skin tones, or brown, purple, grey, or ashen skin in darker skin tones.^{1, 2}

Eczema is quite a prevalent and persistent skin ailment that affects an estimated 35 million Americans.³ Worldwide, 2-5% of adults and around 15% of children have symptoms. It is most frequent in children, although it may happen at any age. It often develops before the age of 5 and may last into adolescence and adulthood. It flares up for some individuals on a regular basis and may subside for years. A personal or family history of eczema, allergies, hay fever, or asthma are major risk factors for atopic dermatitis.

There is no cure for eczema. Treatments and self-care techniques may alleviate irritation and prevent future breakouts. Avoid harsh soaps, moisturise your skin on a regular basis, and use medicated lotions or ointments to assist with symptom management. 

Difference Between Psoriasis and Eczema

Both psoriasis and eczema are connected to the immune system and may create red, itchy and dry areas of skin, but there are several crucial differences. While eczema may cause the skin to be irritated, peeling, cracked, or blistered, it does not usually result in scaly dead skin. Psoriasis, on the other hand, is distinguished by broad areas of silvery scaly skin produced by an accumulation of dead skin cells.⁴ 

There are also a few major distinctions between eczema and psoriasis symptoms. Firstly, although both disorders produce itchy skin, psoriasis also creates a stinging or burning sensation, similar to being stung by fire ants. Secondly, eczema symptoms often occur sooner than psoriasis symptoms. Most individuals have eczema as newborns or toddlers and eventually grow out of it, but psoriasis generally starts between the ages of 15 and 35 and is a lifelong disease.⁴

Whether suffering from eczema or psoriasis, a doctor can offer different therapies. In all circumstances, keeping the skin clean and moisturised, avoiding harsh soaps and extremely hot water, and using a water softener if living in a hard water region will help ease pain and lessen dryness and irritation. Other treatment options for psoriasis include light therapy, and for eczema, lifestyle adjustments (avoiding known allergens, lowering stress, and wearing soft gloves at night if scratching during sleep is an issue). A doctor may also prescribe medicinal lotions and ointments to relieve symptoms in more severe instances.⁴

Types of Eczema

While the actual causes of eczema is unclear, experts do know that individuals with eczema get it as a result of a mix of genetic and environmental factors. Eczema has been classified into 7 types:^5,6,7 

1. Atopic dermatitis 
2. Dermatitis due to contact 
3. Neurodermatitis 
4. Eczema with dyshidrotic keratosis 
5. Nummular eczema 
6. Seborrheic dermatitis 
7. Dermatitis stasis 

Patients might have many types of eczema on their bodies at the same time. Each kind of eczema has its own unique set of triggers and treatment needs, which is why it is critical to work with a healthcare practitioner.² Dermatologists, in particular, can assist in determining the types and the most suitable treatment methods to counter and avoid flare-ups.

Causes and Prevention 

A cause of eczema is a lack of lipids and other substances in the skin's layers that protect the skin's outer barrier. When these components are scarce, germs may enter the skin via fissures. Researchers have found that bacteria in the skin is not just a symptom of eczema, but also a likely cause. Bacteria, once inside, may irritate and inflame the skin. 

Some eczema prevention research focuses on family history and genes. Researchers theorise that certain genes inherited from your parents increase your likelihood of developing eczema. The illness is then triggered by environmental causes. FLG is an essential gene that helps keep the skin wet and inhibits allergies, germs, and other dangerous things from entering. A change or mutation in this gene may increase the likelihood of developing eczema. Scientists have discovered 118 more genes associated with both eczema and psoriasis. They also uncovered KIF3A gene variations that decrease the skin's natural barrier. This causes the skin to lose water and become dry. These genes might help researchers understand more about the causes of eczema and develop novel treatments.⁸

Treatments

Although a new class of drug therapies seems promising, there is insufficient data to advocate using any of them.⁸

Monoclonal Antibodies

Until 2017, the only medications available for eczema were steroids and anti-itch lotions. The FDA then authorised dupilumab (Dupixent), a kind of medication known as a monoclonal antibody. It is injected just under your skin. It inhibits two immune system molecules that induce inflammation in persons with eczema. Lebrikizumab and tralokinumab are two more medications in development that would act in a similar manner. Another medicine, nemolizumab, is still in the experimental phase and works by blocking a protein that causes irritation in eczema. 

Janus Kinase (JAK) Inhibitors

A class of medications known as JAK inhibitors may be the next big thing in eczema therapy. They have the ability to inhibit JAK proteins. In eczema, these compounds cause the production of chemicals that irritate the skin. A few JAK inhibitors are now being tested in late-stage clinical studies for eczema. So far, research has shown that they cleanse the skin and relieve irritation. In one study, an investigational medicine called abrocitinib reduced itch better than Dupixent. Instead of an injection like Dupixent, JAK inhibitors are available as a tablet and a cream. JAK inhibitors are already used to treat rheumatoid and psoriatic arthritis. 

Beneficial Germs

Researchers have known for a long time that persons with atopic dermatitis have a high concentration of staph germs on their skin. These bacteria not only cause infection, but also activate immunological responses which induce swelling and redness. Scientists are now investigating whether beneficial bacteria, known as probiotics, might destroy dangerous bacteria in the skin and hence aid in the treatment of this ailment. Roseomonas mucosa, a species of bacterium studied in mice and human cells, alleviated eczema symptoms and decreased the need for steroid medications in children. Future research should focus on whether bacteria are a safe and effective eczema therapy. 

Alternative Therapies 

Non-drug treatments for eczema redness and irritation are being sought. Several alternative remedies have been demonstrated in trials to be effective, including: 

• Sandalwood 
• Diluted evening primrose essential oil 
• Manuka honey 
• B12, D, and E vitamins 

Genetics of Eczema

Eczema may affect anybody. However, if eczema runs in a person's family, their chances of having eczema rise. According to a 2015 study, the likelihood of inheriting atopic eczema is roughly 75%.⁹ 

While researchers do not completely understand the genetics of eczema, evidence shows that numerous genes may play a role in the condition's development, and that in rare circumstances, a single inherited gene mutation may cause eczema. 

CARD11 is one such gene, which encodes information for the production of a protein required for the normal functioning of lymphocytes. Lymphocytes are immune cells that keep the body healthy by fighting infections. Due to a weaker immune system, mutations in the CARD11 gene may cause atopic eczema. At least five CARD11 mutations have been discovered as being present in persons with atopic eczema. According to a 2017 study, a mutation in one of the two inherited CARD11 genes was adequate to produce atopic eczema.¹⁰ 

KIF3A, which codes for a protein involved in protein transport and cell signalling, is another gene that contributes to the development of eczema. According to a 2020 study, genetic differences in KIF3A may enhance the likelihood of getting atopic dermatitis.¹¹ This is caused by the skin barrier weakening. 

FLG is another gene that may have a role in the development of eczema. Profilaggrin, which generates the protein filaggrin, is encoded by this gene. This protein aids in the preservation of the skin barrier and the hydration of the skin. There is a substantial link between FLG gene mutations and the development of atopic eczema. An FLG gene mutation affects 20–30% of people with atopic eczema. People with mutations in both copies of the FLG gene often have more severe atopic eczema. 

Is Eczema an Autoimmune Disease?

Previous research had revealed that medications that inhibit the immune system widely alleviate symptoms in people with the condition, but the field had not explained the molecular pathways involved in depth. At the molecular level, researchers have shown that atopic dermatitis, often known as eczema, is an autoimmune illness. 

Researchers discovered that dupilumab, a monoclonal antibody therapy that inhibits the function of two important signalling proteins, reversed disease processes shown in patients' skin at the molecular level. Interleukins, one of the types of signalling proteins, are examples of cytokines, which are immune proteins that boost the body's response to invading viruses and bacteria (producing associated inflammation), but may incorrectly target physiological tissues as part of autoimmune illnesses. 

Medications that specifically target these two immune signalling proteins may correct the defects in the skin barrier and immune system that define atopic dermatitis. Patients who received dupilumab saw substantial clinical benefits when compared to those who received a placebo. Within 4 weeks of receiving dupilumab, the abnormalities that define atopic dermatitis in skin tissues were reversed. 

Eczema and Autoimmune Disorders

The researchers looked for 8,112 Danish diagnosed with eczema between 1/Jan/1997 and 31/Dec/2012.¹² Significantly associated with atopic dermatitis are: 

• Alopecia areata
• Vitiligo 
• Chronic urticaria
• Celiac disease 
• Chronic glomerulonephritis 
• Sjögren syndrome 
• Systemic lupus erythematosus 
• Ankylosing spondylitis 
• Crohn's disease 
• Unspecified inflammatory bowel disease 
• Ulcerative colitis
• Rheumatoid arthritis

Atopic dermatitis was also shown to be more closely associated with having three or fewer autoimmune illnesses than with having one or two comorbidities. A smoking history was substantially related to having one or more autoimmune diseases. 

According to the researchers, atopic dermatitis and autoimmune diseases may share genetic risk loci and common environmental triggers due to the common occurrence of autoimmune comorbidities and the association of high living standards and urban lifestyles with atopic dermatitis found in previous studies.

Summary

Atopic dermatitis is a complicated skin disorder caused by abnormalities in the skin's barrier. Multiple intrinsic, as well as extrinsic variables, put persons at risk of developing adverse events (AE), including environmental elements that, in times of climate change, may play an even larger influence in the future.¹³ Many aspects of the complicated disease pathways may have been uncovered in the recent few decades; yet a lot remains unclear and must be addressed.¹³