Atopic Dermatitis: A Systemic Disease

Explore the modern understanding of Atopic Dermatitis (AD) as a complex systemic disorder, driven by a cycle of barrier defects, immune dysregulation, and neuro-immune signaling.

1. Epidermal Barrier Defect

A genetically predisposed "leaky" skin barrier is the initial vulnerability, allowing allergens and microbes to penetrate, triggering the immune system.

2. Immune Dysregulation

The immune system overreacts with a dominant Type 2 inflammation, driven by cytokines like IL-4 and IL-13, which further damages the skin barrier and causes inflammation.

3. The Itch-Scratch Cycle

Inflammation activates specific nerve fibers, causing intense itch (pruritus). Scratching provides temporary relief but causes more skin damage, releasing signals that perpetuate the cycle.

The Science of AD

This section delves into the molecular and cellular mechanisms that drive Atopic Dermatitis. Interact with the diagrams below to understand the key pathological processes, from genetic predispositions to the complex immune and neural signaling cascades.

The Immune Cascade in Atopic Dermatitis

1. The Spark

Damaged keratinocytes release "alarmins" (TSLP, IL-25, IL-33).

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2. Activation

Alarmins activate ILC2s and Dendritic Cells.

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3. Type 2 Dominance

Naive T-cells differentiate into Th2 cells.

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4. Cytokine Storm

Overproduction of IL-4, IL-13, IL-5, and IL-31.

The Clinical Picture

Here we explore how Atopic Dermatitis presents in patients, the criteria for diagnosis, and its impact beyond the skin. This section aims to provide a comprehensive view of the patient experience and the clinical heterogeneity of the disease.

Diagnostic Criteria

Diagnosis via Hanifin & Rajka criteria requires 3+ major and 3+ minor criteria.

Major Criteria

  • Pruritus (itching)
  • Typical morphology and distribution
  • Chronic or chronically-relapsing course
  • Personal or family history of atopy

Key Minor Criteria

  • Xerosis (dry skin)
  • Early age of onset
  • Elevated serum IgE
  • Susceptibility to skin infections

Disease Heterogeneity

AD is not one-size-fits-all. It presents in different forms (phenotypes) and is driven by different molecular pathways (endotypes).

Common Phenotypes

  • Nummular Eczema: Coin-shaped lesions.
  • Follicular Eczema: Prominent in skin of color.
  • Prurigo Nodularis: Intensely itchy, hard nodules.

Key Endotypes

  • Extrinsic AD (~80%): Classic allergic form with high IgE.
  • Intrinsic AD (~20%): Normal IgE, no specific sensitization.

The Therapeutic Arsenal

The treatment landscape for AD has been revolutionized by targeted therapies. This section provides an interactive overview of the modern therapeutic options, from biologics to small molecules, and a look at the future of treatment.

Treatment Efficacy Comparison

Comparing key systemic therapies based on clinical trial data for moderate-to-severe AD.

References

The information in this application is based on the provided report and additional research from the following sources, reflecting the latest advancements in atopic dermatitis.