Emerging concepts in atopic dermatitis and atopic keratoconjunctivitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cytokine-driven inflammation. AD patients are at risk of developing conjunctivitis, including atopic keratoconjunctivitis (AKC), a sight-threatening chronic allergic eye disease involving both Th2 and Th1/17 cytokine-driven inflammation.In AD, dupilumab is highly effective by inhibiting interleukin (IL)-4 and IL-13. However, some AD patients develop dupilumab-associated ocular surface disease (DAOSD), an AKC-like disease. There are no biomarkers to predict who will develop DAOSD. The purpose of this review is to highlight recent findings in AD and AKC suggesting different immunopathogenic mechanisms are involved.

A recent proteomics study of tear fluids identified raised inflammatory markers ( n  = 31) in AD patients with DAOSD ( n  = 22) and a shift towards a Th1/17 profile. Alternative biologics have been investigated for treating moderate-to-severe AD which have fewer ocular side-effects. The inhibitory effects of dupilumab cause an associated upregulation of IL-33 which could lead to an AKC-like disease. A recent therapeutic approach in AD via regulatory T cells suggests a novel treatment for those at risk of DAOSD.

Ocular side-effects of dupilumab suggest that the immunopathogenic pathways in moderate-to-severe AD and AKC are not the same and, for DAOSD, might require different treatment approaches.