Atopic dermatitis

With atopic dermatitis, dermatitis refers to skin inflammation, while “atopic” comes from the Greek word “atopia” meaning “out of place”. This phrase reflects the idea that in atopic dermatitis, the immune system overreacts to everyday, harmless substances, such as dust and pollen, as if they were dangerous, subsequently triggering inflammation and an extremely itchy rash. Atopic dermatitis, also known as atopic eczema, is a chronic, relapsing skin condition that’s particularly common among young children, but it can also persist well into adulthood.

Now, the skin is the body’s natural barrier that protects you from environmental substances and microbes. The outer layer of your skin called the epidermis, has four layers stacked up like a protective team. At the bottom is the stratum basale, followed by the stratum spinosum, then the stratum granulosum. The outermost layer and the front line of the skin barrier is the stratum corneum. Think of it as a brick wall. In this wall, bricks represent dead, flattened skin cells called corneocytes, which lock in moisture and keep allergens, irritants, and microbes out. But even the strongest wall needs reinforcement, and that’s where filaggrin comes in. This special protein works like rebar inside the wall. It links neighboring cells, flattens them out, and gives the skin its strength and flexibility.

At the heart of atopic dermatitis is a complex interaction between genetics, environmental factors, and the immune system.

On the genetic side, many individuals have mutations in the gene that encodes filaggrin. Without enough functional filaggrin, the wall loses its strength and cracks open leaving our body vulnerable. In other words, the skin loses its ability to retain moisture and keep out harmful substances.

Moreover, this compromised skin barrier opens the door to environmental triggers and allergens, such as dust mites and pollen. But here’s the thing. The immune system is always on alert, with antigen-presenting cells as frontline scouts constantly gathering intelligence on potential threats.

So, when something makes its way through the damaged skin, these immune scouts spring into action. They capture the intruder through a process called phagocytosis and break it down. Next, they present some of its fragments, known as antigens, on their surface. It’s their way of signalling to the immune system: “We have an intruder!” Using these antigens, they alert Th2 helper T cells to release pro-inflammatory cytokines called interleukins, which signal other immune cells to jump into action.

Interleukin 5 activates eosinophils to join the response, while interleukins 4 and 13 stimulate B cells to differentiate into plasma cells. Next, these plasma cells begin producing allergen-specific IgE antibodies, which latch onto mast cells and prepare them for future encounters.

When the body meets the same allergen again, the allergen cross-links the IgE on the surface of mast cells, triggering the release of histamine and other inflammatory mediators. This IgE-mediated immune response, known as type I hypersensitivity, results in the hallmark symptoms of atopic dermatitis, including erythema, swelling, and intense itching. Itching leads to scratching, and scratching makes things worse by further damaging the already fragile skin barrier.

Additionally, a sneaky bacterium called Staphylococcus aureus takes advantage of the cracked skin. The bacterium colonizes damaged areas and releases toxins that stimulate the immune system even more, adding fuel to the already raging fire of inflammation.

But the immune system doesn’t stop at the skin. If a person keeps encountering the same allergen, the reaction can escalate, and the immune response can spread beyond the skin. This occurs when Th2 cells slip into the bloodstream and travel to the lungs, where they can trigger asthma. Later, they can reach the nasal passages and cause allergic rhinitis. This step-by-step progression is called the atopic march.