Atopic Dermatitis Treatment Options

Atopic Dermatitis Treatment Options

Non-Pharmacological Treatment

  • Trigger Avoidance: Identify and avoid factors that trigger flares.
  • Clothing: Wear soft, loose-fitting clothing.
  • Environmental Control:
    • Avoid heat and rapidly changing weather.
    • Manage humid environments.
  • Bathing: Short, frequent showers with dispersible oils.
  • Moisturization:
    • Wet compresses and wraps to keep skin moist.
    • Barrier creams and emollients (moisturizers) to protect and hydrate skin.
  • Irritant Avoidance: Avoid soaps, shampoo substitutes, and cosmetic products that can trigger flares.

Pharmacological Treatment

Antihistamines for Itch (Pruritus)
  • Considerations: Itch intensity and patient age.
  • Options:
    • Children (
    • Adults (intense itch): Sedating antihistamines (e.g., promethazine).
  • Crotamiton: Topical antipruritic, commonly used for scabies-related itch.
Pain Management
  • Options: Paracetamol or non-selective NSAIDs (e.g., ibuprofen), but evidence of effectiveness is limited.
  • Goal: Control inflammation to reduce pain.
Corticosteroids
  • Mainstay Treatment: Similar to contact dermatitis.
  • Administration: Topical corticosteroids.
  • Mechanism of Action & Adverse Effects: As previously discussed (in prior lectures).
Topical Anti-inflammatory (TA) Preparations
  • Examples: COTA, Ichthammol, WUT TA.
  • Mechanism of Action (historical view): Suppresses DNA synthesis, promoting normal keratinization.
  • Additional activities: Anti-pruritic (relief for itching), softens scales/crusts, prevents microbial growth
  • Sensory Issues: They have strong odd acidic odors that some patient may not tolerate, stain can be a problem because of their thickness and viscosity.
  • COTA (Coal Tar)
    • Contains complex aromatic hydrocarbons.
    • Photosensitivity: Exposure to UV rays excites hydrocarbons, releasing reactive oxygen species, increasing risk of inflammation and acne.
  • Ichthammol
    • Contains a phenolic group.
    • Less photosensitizing than COTA.
    • Increased absorption: The phenolic group increases skin absorption, making it potentially more irritating and toxic than COTA.
Crisaborole (Phosphodiesterase-4 Inhibitor)
  • Mechanism of Action:
    • Inhibits phosphodiesterase-4 (PDE4) enzyme.
    • PDE4 normally converts cAMP to AMP in T cells.
    • AMP inhibits Protein Kinase A
    • Protein Kinase A activates genetic factor, Nuclear Factor of Activated T-cells (NFAT) and Nuclear Factor Kappa Beta (NF$\kappa$B)
    • These result in pro-inflammatory mediator release (cytokines).
  • Crisaborole Effect:
    • Inhibits PDE4, increasing cAMP.
    • Increases Protein Kinase A activation.
    • Inhibits the genetic transcription factors NFAT and NFkB, reducing pro-inflammatory mediator synthesis.
    • Examples of pro-inflammatory mediators:
      • T Helper 2 cells: IL-4, IL-5, IL-13.
      • T Helper 1 cells: TNF-$\alpha$.
Calcineurin Inhibitors
  • Drugs: Cyclosporine, Pimecrolimus, Tacrolimus.
  • Mechanism of Action:
    • Calcineurin activates Nuclear Factor of Activated T-cells (NFAT) in T cells.
    • Activated NFAT stimulates genetic transcription, synthesizing pro-inflammatory mediators (e.g., TNF$\alpha$, IL-2, IL-4, IL-5, IL-13, IL-23).
    • Calcineurin inhibitors inactivate calcineurin.
    • Cyclosporine: Binds to cyclophilin to inhibit calcineurin.
    • Pimecrolimus & Tacrolimus: Bind to immunophilin (FKBP) to inhibit calcineurin.
    • Inhibition of calcineurin prevents NFAT activation, inhibiting pro-inflammatory mediator synthesis.
  • Cyclosporine
    • Administration: Oral, leading to systemic exposure.
    • Potent Immunosuppressant: Significant toxicities.
    • Adverse Effects:
      • Immunosuppression (increased risk of infection).
      • Neurotoxicity: Stimulates endothelin release from endothelial cells (vasoconstriction, neuronal damage, hypertension).
      • Nephrotoxicity & Hepatotoxicity: damages Kidney and Liver.
      • Drug Interactions: Substrate of CYP3A4 enzyme.
  • Tacrolimus & Pimecrolimus
    • Administration: Topical calcineurin inhibitors.
    • Inhibit NFAT by binding to FKBP immunophilin.
    • Tacrolimus is generally more effective than pimecrolimus.
      • More Lipophilic: Pemacrolimus accumulates in the epidermal layer, with limited penetration across the skin.
      • More Hydrophilic: Tacrolimus penetrates the skin better (higher concentration in skin).
    • Adverse Effects: Erythema, irritation, photosensitivity
Monoclonal Antibodies
  • Drugs: Dupilumab, Tralokinumab
  • Dupilumab: Inhibits IL-4 and IL-13, limiting atopic inflammation and immune responses.
  • Tralokinumab: Specifically inhibits IL-13.
  • Ineffective drugs : Legolizumab inhibits IgE.
  • Other Monoclonal Antibodies (Not yet indicated for Atopic Dermatitis): Ustekinumab (inhibits IL-12 and IL-23).
  • Adverse Effects (Dupilumab & Tralokinumab): Dry eyes and blepharitis (red, swollen, irritated eyes/eyelids).
    • Mechanism: IL-13 maintains goblet cell density in conjunctiva epithelium. Inhibition reduces goblet cell density, increasing dry/itchy eyes.