Emerging concepts in atopic dermatitis and atopic keratoconjunctivitis.

Area of Science:

• Immunology
• Ophthalmology
• Dermatology

Background:

• Atopic dermatitis (AD) involves Th2 inflammation and can lead to atopic keratoconjunctivitis (AKC), a severe allergic eye condition.
• Dupilumab effectively treats AD by inhibiting IL-4 and IL-13 but can paradoxically cause dupilumab-associated ocular surface disease (DAOSD), an AKC-like condition.
• Currently, no biomarkers predict DAOSD development in AD patients treated with dupilumab.

Purpose of the Study:

• To review recent findings in AD and AKC to understand differing immunopathogenic mechanisms.
• To explore potential reasons for DAOSD development in AD patients undergoing dupilumab therapy.

Main Methods:

• Analysis of recent proteomics studies on tear fluid in AD patients with and without DAOSD.
• Review of current literature on alternative biologic treatments for AD with fewer ocular side effects.
• Investigation into the role of IL-33 upregulation and regulatory T cell therapies in AD and associated ocular conditions.

Main Results:

• Proteomics identified elevated inflammatory markers and a shift towards Th1/17 profiles in AD patients with DAOSD.
• Dupilumab's inhibition of IL-4/IL-13 may lead to IL-33 upregulation, potentially causing AKC-like disease.
• Alternative biologics and regulatory T cell-based therapies are being explored for AD management with reduced ocular risks.

Conclusions:

• The immunopathogenic pathways in AD and AKC differ, particularly in DAOSD.
• DAOSD may necessitate distinct treatment strategies separate from standard AD or AKC management.
• Further research into biomarkers and targeted therapies is crucial for managing AD-related ocular complications.