Atopic dermatitis, commonly known as eczema, is a chronic inflammatory skin condition affecting millions worldwide. It causes dry, intensely itchy, and inflamed skin, often appearing as red, scaly patches. This condition arises from a complex interplay of genetic predispositions, environmental factors, and immune system abnormalities.
Skin Barrier Compromise
The skin serves as the body’s primary protective barrier, preventing water loss and blocking the entry of harmful substances. In atopic dermatitis, this barrier is often compromised, leading to increased vulnerability. Genetic factors play a significant role in this dysfunction, particularly mutations in the FLG gene, which provides instructions for making filaggrin.
Filaggrin is a protein that helps form a strong, resilient outer layer of the skin, the stratum corneum. It also breaks down into natural moisturizing factors, which help the skin retain water. When filaggrin is deficient due to genetic mutations, the skin barrier becomes structurally weak and less effective at holding moisture. This deficiency results in increased transepidermal water loss, causing the characteristic dryness of atopic dermatitis.
A compromised barrier also means environmental allergens, irritants, and bacteria can more easily penetrate the skin’s surface. These substances reach deeper layers, triggering immune responses and inflammation. Beyond filaggrin, the lipid composition of the skin barrier, particularly ceramides, is also altered. These lipids are important for maintaining the skin’s integrity and sealing gaps between skin cells, and their disruption further impairs barrier function.
Immune System Dysregulation
Beyond barrier issues, the immune system in atopic dermatitis exhibits distinct overactivity and imbalance. This condition is characterized by a “Type 2” immune response, which typically involves allergic reactions. T helper 2 (Th2) cells are a primary driver of this response, producing signaling molecules called cytokines.
Key cytokines produced by Th2 cells include Interleukin-4 (IL-4) and Interleukin-13 (IL-13). These molecules promote skin inflammation and stimulate B cells to produce large amounts of immunoglobulin E (IgE) antibodies. Elevated IgE levels in atopic dermatitis contribute significantly to the inflammatory cascade.
Another important cytokine, Interleukin-31 (IL-31), also produced by Th2 cells, directly contributes to the intense itching of atopic dermatitis. This cytokine acts on nerve endings in the skin, initiating itch signals to the brain.
Once IgE antibodies are produced, they bind to mast cells, immune cells abundant in the skin. When allergens re-enter the compromised skin, they can cross-link IgE on mast cells, causing them to release inflammatory mediators like histamine. Eosinophils are also often found in increased numbers in the skin. These cells release toxic proteins and inflammatory molecules that contribute to tissue damage and chronic inflammation. This network of immune cells and their signaling molecules sustains the inflammation and allergic reactions in atopic dermatitis.
Role of the Microbiome and Itch-Scratch Cycle
The skin’s surface is home to a diverse community of microorganisms known as the skin microbiome. In atopic dermatitis, this microbial balance is often disrupted, a condition referred to as dysbiosis. A notable feature of this dysbiosis is the overgrowth of Staphylococcus aureus bacteria. This bacterium is frequently found on the skin.
Staphylococcus aureus contributes to inflammation and barrier disruption through various mechanisms. It can produce toxins and enzymes that further break down the skin barrier, making it more permeable. These bacterial products also trigger immune cells to release inflammatory cytokines, exacerbating the skin’s inflammatory state. The presence of Staphylococcus aureus can also increase susceptibility to secondary skin infections, which further complicate the condition.
The intense itching, or pruritus, is a hallmark symptom of atopic dermatitis and is intricately linked to a perpetuating itch-scratch cycle. The initial itch sensation, often driven by immune activation and barrier dysfunction, prompts individuals to scratch the affected areas. This scratching, while providing temporary relief, physically damages the already fragile skin barrier.
Repeated scratching further disrupts the skin’s integrity, creating small abrasions and increasing transepidermal water loss. This damage allows more allergens, irritants, and microbes, including Staphylococcus aureus, to penetrate the skin, which in turn triggers more inflammation and intensifies the itch. The cycle reinforces itself, making the condition chronic and challenging to manage, as scratching perpetuates both inflammation and the sensation of itch.